J Pathol Transl Med.  2023 Jan;57(1):1-27. 10.4132/jptm.2022.12.23.

A standardized pathology report for gastric cancer: 2nd edition

Affiliations
  • 1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 2Center for Gastric Cancer, National Cancer Center, Goyang, Korea
  • 3Department of Pathology, Korea University Guro Hospital, Seoul, Korea
  • 4Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
  • 5Department of Pathology, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Sejong, Korea
  • 6Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea
  • 7Department of Hospital Pathology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
  • 8Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
  • 9Department of Pathology, Dankook University College of Medicine, Cheonan, Korea
  • 10Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
  • 11Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 12Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
  • 13LabGenomics Clinical Laboratories, Seongnam, Korea
  • 14St. Maria Pathology Laboratory, Busan, Korea
  • 15Department of Pathology, Soonchunhyang University Seoul Hospital, Seoul, Korea
  • 16Department of Pathology, Inha University School of Medicine, Incheon, Korea
  • 17Department of Pathology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
  • 18Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
  • 19Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
  • 20Department of Pathology, Dong-A University College of Medicine, Busan, Korea
  • 21Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea
  • 22Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 23Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea

Abstract

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Keyword

Stomach neoplasms; Gastrectomy; Endoscopic resection; Molecular pathology; Pathology report; Standardization

Figure

  • Fig. 1. An example of a tumor deposit. It usually has irregular outlines without identifiable lymph node tissue or identifiable vascular or neural structures.

  • Fig. 2. Histologic features of lymphovascular invasion in sections of gastric cancer. An example of lymphovascular invasion on hematoxylin and eosin examination (A) and stained for D2-40 (B). Tumors involving vessels with an identifiable smooth muscle layer are considered to have venous invasion (C).

  • Fig. 3. Sectioning of an endoscopically resected specimen. When the direction of the photograph matches the direction of the closest lateral margin (A). If the direction of the photograph does not match, turn the specimen toward the closest lateral margin for mapping (B).

  • Fig. 4. Method to measure submucosal invasion depth. Always use the lowest surface of the original, unmodified muscularis mucosae as the reference point (A). When the progressing course of the adjacent muscularis mucosae forms a curve, the virtual line is set as a matching curve (B).

  • Fig. 5. Method to measure submucosal invasion width. The actual size measured within the slide (A). Number of slices that the invasion spans × 2 mm (thickness of slice) (B).

  • Fig. 6. Method to measure ulcer size. The actual size measured within the slide (arrow: ulcer size within the slide) (A). Number of slices that the ulcer spans × 2 mm (thickness of slice) (star: ulcer-positive slices, arrow: slices that the ulcer spans) (B).

  • Fig. 7. Representative pictures of each histologic subtype of gastric carcinoma. Tubular adenocarcinoma (A), papillary adenocarcinoma (B), mucinous adenocarcinoma (C), poorly cohesive carcinoma, not otherwise specified (D), poorly cohesive carcinoma, signet-ring cell type (E), adenocarcinoma with lymphoid stroma (F), hepatoid adenocarcinoma (G), micropapillary adenocarcinoma (H), adenocarcinoma of the fundic- gland type (I, J), undifferentiated carcinoma (K), and crawling-type adenocarcinoma (L).

  • Fig. 8. Grading of gastric tubular adenocarcinoma. Well-differentiated adenocarcinoma showing glandular structures composed of columnar tumor cells (A). Moderately differentiated adenocarcinoma exhibits more complex tubular structures with cuboidal and/or flat epithelial cells (B). Tubular structure is unclear in most tumor glands in poorly differentiated adenocarcinoma (C).

  • Fig. 9. Intestinal (A) and diffuse (B) Lauren type gastric adenocarcinomas characterized by well-formed tumor glands and interspersed tumor cells, respectively.

  • Fig. 10. Tubular adenoma with low-grade dysplasia shows simple tubular architecture composed of elongated tumor cells with preserved polarity (A). More crowding and variation in the size of the tumor glands are noted in high-grade adenoma (B). The diagnosis of adenocarcinoma can be made when tumor cells show single-cell infiltration into the lamina propria (C) and/or marked structural fusion and atypia (D).

  • Fig. 11. Representative images of human epidermal growth factor receptor 2 (HER2)–positive gastric cancer. HER2 immunohistochemistry (IHC) of this case showed heterogeneous intratumoral expression, composed of some areas featuring a score of 2+ with HER2 gene amplification and others scoring 0 (A). HER2 IHC of this case showed homogenous HER2 positivity (score of 3+) (B).

  • Fig. 12. A representative figure of gastric cancer with DNA mismatch repair deficiency. Immunohistochemistry for MLH1 (A) and PMS2 (B) showed loss of nuclear expression in tumor cells and positive nuclear expression in adjacent inflammatory cells. In contrast, immunohistochemistry for MSH2 (C) and MSH6 (D) showed retained nuclear expression in tumor cells. MLH, mutL homolog 1; PMS2, PMS1 homolog 2; MSH2, mutS homolog 2; MSH6, mutS homolog 6.

  • Fig. 13. A representative figure of Epstein-Barr virus (EBV) in situ hybridization. Diffuse positive EBV-encoded small RNA (EBER) signals (A). Heterogenous pattern of EBER signals in cancer cells. EBER signals appear within a few intratumoral lymphocytes (B).

  • Fig. 14. A representative example of programmed death ligand 1 staining. Combined positive score (CPS) < 1 (A), CPS > 1 and < 5 (B), CPS > 5 (C).


Reference

References

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71:209–49.
Article
2. Hong S, Won YJ, Lee JJ, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2018. Cancer Res Treat. 2021; 53:301–15.
Article
3. Kim WH, Park CK, Kim YB, et al. A standardized pathology report for gastric cancer. Korean J Pathol. 2005; 39:106–13.
4. World Health Organization. WHO classification of tumours: digestive system tumours. Geneva: World Health Organization;2019.
5. Guideline Committee of the Korean Gastric Cancer Association (KGCA); Development Working Group and Review Panel. Korean practice guideline for fastric cancer 2018: an evidence-based, multi-disciplinary approach. J Gastric Cancer. 2019; 19:1–48.
6. Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016; 17:717–26.
Article
7. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376:687–97.
Article
8. Amin MB, Edge SB, Greene FL, et al. AJCC cancer staging manual. 8th ed. Cham: Springer;2017.
9. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011; 14:101–12.
10. Fritz A, Percy C, Jack A, et al. International Classification of Diseases for Oncology (ICD-O). 3rd ed. Lyon: International Agency for Research on Cancer;2013.
11. Shi C, Berlin J, Branton PA, et al. Protocol for the examination of specimens from patients with carcinoma of the stomach [Internet]. Northfield: College of American Pathologists;2020. [cited 2022 Dec 1]. Available from: https://documents.cap.org/protocols/cp-giupper-esophagus-20-4100.pdf.
12. Shi C, Badgwell BD, Grabsch HI, et al. Data set for reporting carcinoma of the stomach in gastrectomy. Arch Pathol Lab Med. 2022; 146:1072–83.
Article
13. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006; 355:11–20.
Article
14. Zhang X, Liang H, Li Z, et al. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021; 22:1081–92.
Article
15. Kang YK, Yook JH, Park YK, et al. PRODIGY: a phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. J Clin Oncol. 2021; 39:2903–13.
Article
16. Langer R, Becker K. Tumor regression grading of gastrointestinal cancers after neoadjuvant therapy. Virchows Arch. 2018; 472:175–86.
Article
17. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer. 1994; 73:2680–6.
Article
18. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997; 12:19–23.
Article
19. Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003; 98:1521–30.
Article
20. Mirza A, Naveed A, Hayes S, et al. Assessment of histopathological response in gastric and gastro-oesophageal junction adenocarcinoma following neoadjuvant chemotherapy: which scoring system to use? ISRN Pathol. 2012; 2012:519351.
Article
21. Karamitopoulou E, Thies S, Zlobec I, et al. Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: comparison of 2 commonly used scoring approaches. Am J Surg Pathol. 2014; 38:1551–6.
22. Kim BH, Kim JM, Kang GH, et al. Standardized pathology report for colorectal cancer, 2nd edition. J Pathol Transl Med. 2020; 54:1–19.
Article
23. Tsekrekos A, Vieth M, Ndegwa N, et al. Interobserver agreement of a gastric adenocarcinoma tumor regression grading system that incorporates assessment of lymph nodes. Hum Pathol. 2021; 116:94–101.
Article
24. Davies AR, Myoteri D, Zylstra J, et al. Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma. Br J Surg. 2018; 105:1639–49.
Article
25. Reim D, Novotny A, Friess H, et al. Significance of tumour regression in lymph node metastases of gastric and gastro-oesophageal junction adenocarcinomas. J Pathol Clin Res. 2020; 6:263–72.
Article
26. Smyth EC, Fassan M, Cunningham D, et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council adjuvant gastric infusional chemotherapy Trial. J Clin Oncol. 2016; 34:2721–7.
Article
27. Koh YW, Park YS, Ryu MH, et al. Postoperative nodal status and diffuse-type histology are independent prognostic factors in resectable advanced gastric carcinomas after preoperative chemotherapy. Am J Surg Pathol. 2013; 37:1022–9.
Article
28. Veronese N, Fassan M, Wood LD, et al. Extranodal extension of nodal metastases is a poor prognostic indicator in gastric cancer: a systematic review and meta-analysis. J Gastrointest Surg. 2016; 20:1692–8.
Article
29. Lee IS, Park YS, Ryu MH, et al. Impact of extranodal extension on prognosis in lymph node-positive gastric cancer. Br J Surg. 2014; 101:1576–84.
Article
30. Lee IS, Kang HJ, Park YS, et al. Prognostic impact of extranodal extension in stage 1B gastric carcinomas. Surg Oncol. 2018; 27:299–305.
Article
31. Araki I, Hosoda K, Yamashita K, et al. Prognostic impact of venous invasion in stage IB node-negative gastric cancer. Gastric Cancer. 2015; 18:297–305.
Article
32. Takeuchi A, Ojima T, Katsuda M, et al. Venous invasion is a risk factor for recurrence of pT1 gastric cancer with lymph node metastasis. J Gastrointest Surg. 2022; 26:757–63.
Article
33. Nishibeppu K, Komatsu S, Ichikawa D, et al. Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer. BMC Cancer. 2018; 18:108.
Article
34. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer. 2009; 115:3379–91.
35. Hanaoka N, Tanabe S, Mikami T, Okayasu I, Saigenji K. Mixedhistologic-type submucosal invasive gastric cancer as a risk factor for lymph node metastasis: feasibility of endoscopic submucosal dissection. Endoscopy. 2009; 41:427–32.
Article
36. Takizawa K, Ono H, Kakushima N, et al. Risk of lymph node metastases from intramucosal gastric cancer in relation to histological types: how to manage the mixed histological type for endoscopic submucosal dissection. Gastric Cancer. 2013; 16:531–6.
Article
37. Lee JH, Choi IJ, Han HS, et al. Risk of lymph node metastasis in differentiated type mucosal early gastric cancer mixed with minor undifferentiated type histology. Ann Surg Oncol. 2015; 22:1813–9.
Article
38. Sekiguchi M, Oda I, Taniguchi H, et al. Risk stratification and predictive risk-scoring model for lymph node metastasis in early gastric cancer. J Gastroenterol. 2016; 51:961–70.
Article
39. Seo HS, Lee GE, Kang MG, Han KH, Jung ES, Song KY. Mixed histology is a risk factor for lymph node metastasis in early gastric cancer. J Surg Res. 2019; 236:271–7.
Article
40. Horiuchi Y, Ida S, Yamamoto N, et al. Feasibility of further expansion of the indications for endoscopic submucosal dissection in undifferentiated-type early gastric cancer. Gastric Cancer. 2020; 23:285–92.
Article
41. Ha TK, An JY, Youn HK, Noh JH, Sohn TS, Kim S. Indication for endoscopic mucosal resection in early signet ring cell gastric cancer. Ann Surg Oncol. 2008; 15:508–13.
Article
42. Kim BS, Oh ST, Yook JH, Kim BS. Signet ring cell type and other histologic types: differing clinical course and prognosis in T1 gastric cancer. Surgery. 2014; 155:1030–5.
Article
43. Guo CG, Zhao DB, Liu Q, et al. Risk factors for lymph node metastasis in early gastric cancer with signet ring cell carcinoma. J Gastrointest Surg. 2015; 19:1958–65.
Article
44. Huh CW, Jung DH, Kim JH, et al. Signet ring cell mixed histology may show more aggressive behavior than other histologies in early gastric cancer. J Surg Oncol. 2013; 107:124–9.
Article
45. Lee IS, Lee S, Park YS, Gong CS, Yook JH, Kim BS. Applicability of endoscopic submucosal dissection for undifferentiated early gastric cancer: Mixed histology of poorly differentiated adenocarcinoma and signet ring cell carcinoma is a worse predictive factor of nodal metastasis. Surg Oncol. 2017; 26:8–12.
Article
46. Kim YH, Park JH, Park CK, et al. Histologic purity of signet ring cell carcinoma is a favorable risk factor for lymph node metastasis in poorly cohesive, submucosa-invasive early gastric carcinoma. Gastric Cancer. 2017; 20:583–90.
Article
47. Chu Y, Mao T, Li X, et al. Predictors of lymph node metastasis and differences between pure and mixed histologic types of early gastric signet-ring cell carcinomas. Am J Surg Pathol. 2020; 44:934–42.
Article
48. Japanese Gastric Cancer Society. Regulations for the treatment of gastric cancer. 15th ed. Tokyo: Kanehara Publishing;2017.
49. Kim JY, Kim WG, Jeon TY, et al. Lymph node metastasis in early gastric cancer: evaluation of a novel method for measuring submucosal invasion and development of a nodal predicting index. Hum Pathol. 2013; 44:2829–36.
Article
50. Ma DW, Lee SJ, Kook MC, et al. The suggestion of revised criteria for endoscopic resection of differentiated-type submucosal gastric cancer. Ann Surg Oncol. 2020; 27:795–801.
Article
51. Choi JY, Park YS, Jung HY, et al. Identifying predictors of lymph node metastasis after endoscopic resection in patients with minute submucosal cancer of the stomach. Surg Endosc. 2015; 29:1476–83.
Article
52. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer. 2000; 3:219–25.
Article
53. Park SM, Kim BW, Kim JS, Kim YW, Kim GJ, Ryu SJ. Can endoscopic ulcerations in early gastric cancer be clearly defined before endoscopic resection? A survey among endoscopists. Clin Endosc. 2017; 50:473–8.
Article
54. Kim JM, Sohn JH, Cho MY, et al. Pre- and post-ESD discrepancies in clinicopathologic criteria in early gastric cancer: the NECA-Korea ESD for Early Gastric Cancer Prospective Study (NKeep). Gastric Cancer. 2016; 19:1104–13.
Article
55. Yabuuchi Y, Takizawa K, Kakushima N, et al. Discrepancy between endoscopic and pathological ulcerative findings in clinical intramucosal early gastric cancer. Gastric Cancer. 2021; 24:691–700.
Article
56. Shimoda T, Kushima R, Ono H. Histological features of peptic ulceration and biopsy scar of gastric ESD specimen. Stomach Intestine. 2013; 48:16–24.
57. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2021; 24:1–21.
58. Takizawa K, Ono H, Hasuike N, et al. A nonrandomized, singlearm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer: Japan Clinical Oncology Group study (JCOG1009/1010). Gastric Cancer. 2021; 24:479–91.
Article
59. Hatta W, Gotoda T, Oyama T, et al. A scoring system to stratify curability after endoscopic submucosal dissection for early gastric cancer: "eCura system". Am J Gastroenterol. 2017; 112:874–81.
Article
60. Uesugi N, Sugai T, Sugimoto R, et al. Clinicopathological and molecular stability and methylation analyses of gastric papillary adenocarcinoma. Pathology. 2017; 49:596–603.
Article
61. Lee HJ, Kim GH, Park DY, et al. Endoscopic submucosal dissection for papillary adenocarcinoma of the stomach: is it really safe? Gastric Cancer. 2017; 20:978–86.
Article
62. Min BH, Byeon SJ, Lee JH, et al. Lymphovascular invasion and lymph node metastasis rates in papillary adenocarcinoma of the stomach: implications for endoscopic resection. Gastric Cancer. 2018; 21:680–8.
Article
63. Yasuda K, Adachi Y, Shiraishi N, Maeo S, Kitano S. Papillary adenocarcinoma of the stomach. Gastric Cancer. 2000; 3:33–8.
Article
64. Yu H, Fang C, Chen L, et al. Worse prognosis in papillary, compared to tubular, early gastric carcinoma. J Cancer. 2017; 8:117–23.
Article
65. Kawamura H, Kondo Y, Osawa S, et al. A clinicopathologic study of mucinous adenocarcinoma of the stomach. Gastric Cancer. 2001; 4:83–6.
Article
66. Lee HH, Song KY, Park CH, Jeon HM. Undifferentiated-type gastric adenocarcinoma: prognostic impact of three histological types. World J Surg Oncol. 2012; 10:254.
Article
67. Nakamura K, Eto K, Iwagami S, et al. Clinicopathological characteristics and prognosis of poorly cohesive cell subtype of gastric cancer. Int J Clin Oncol. 2022; 27:512–9.
Article
68. Roviello F, Marano L, Ambrosio MR, et al. Signet ring cell percentage in poorly cohesive gastric cancer patients: a potential novel predictor of survival. Eur J Surg Oncol. 2022; 48:561–9.
Article
69. Garcia-Pelaez J, Barbosa-Matos R, Gullo I, Carneiro F, Oliveira C. Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges. Mol Oncol. 2021; 15:2841–67.
Article
70. Kwon CH, Kim YK, Lee S, et al. Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes. Histopathology. 2018; 72:556–68.
Article
71. Mariette C, Carneiro F, Grabsch HI, et al. Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma. Gastric Cancer. 2019; 22:1–9.
Article
72. Han JP, Hong SJ, Kim HK. Long-term outcomes of early gastric cancer diagnosed as mixed adenocarcinoma after endoscopic submucosal dissection. J Gastroenterol Hepatol. 2015; 30:316–20.
Article
73. Park HK, Lee KY, Yoo MW, Hwang TS, Han HS. Mixed carcinoma as an independent prognostic factor in submucosal invasive gastric carcinoma. J Korean Med Sci. 2016; 31:866–72.
Article
74. Horiuchi Y, Fujisaki J, Yamamoto N, et al. Undifferentiated-type predominant mixed-type early gastric cancer is a significant risk factor for requiring additional surgeries after endoscopic submucosal dissection. Sci Rep. 2020; 10:6748.
Article
75. Ozeki Y, Hirasawa K, Sawada A, et al. Mixed histology poses a greater risk for noncurative endoscopic resection in early gastric cancers regardless of the predominant histologic types. Eur J Gastroenterol Hepatol. 2021; 32:186–93.
Article
76. Shin DH, Kim GH, Lee BE, et al. Clinicopathologic features of early gastric carcinoma with lymphoid stroma and feasibility of endoscopic submucosal dissection. Surg Endosc. 2017; 31:4156–64.
Article
77. Iwasaki K, Suda T, Takano Y, et al. Postoperative outcomes of gastric carcinoma with lymphoid stroma. World J Surg Oncol. 2020; 18:102.
Article
78. Huh CW, Jung DH, Kim H, et al. Clinicopathologic features of gastric carcinoma with lymphoid stroma in early gastric cancer. J Surg Oncol. 2016; 114:769–72.
Article
79. Inagawa S, Shimazaki J, Hori M, et al. Hepatoid adenocarcinoma of the stomach. Gastric Cancer. 2001; 4:43–52.
Article
80. Roh JH, Srivastava A, Lauwers GY, et al. Micropapillary carcinoma of stomach: a clinicopathologic and immunohistochemical study of 11 cases. Am J Surg Pathol. 2010; 34:1139–46.
81. Fujita T, Gotohda N, Kato Y, et al. Clinicopathological features of stomach cancer with invasive micropapillary component. Gastric Cancer. 2012; 15:179–87.
Article
82. Benedict MA, Lauwers GY, Jain D. Gastric adenocarcinoma of the fundic gland type: update and literature review. Am J Clin Pathol. 2018; 149:461–73.
83. Miyazawa M, Matsuda M, Yano M, et al. Gastric adenocarcinoma of the fundic gland (chief cell-predominant type): a review of endoscopic and clinicopathological features. World J Gastroenterol. 2016; 22:10523–31.
Article
84. Agaimy A, Rau TT, Hartmann A, Stoehr R. SMARCB1 (INI1)- negative rhabdoid carcinomas of the gastrointestinal tract: clinicopathologic and molecular study of a highly aggressive variant with literature review. Am J Surg Pathol. 2014; 38:910–20.
85. Willems S, Carneiro F, Geboes K. Gastric carcinoma with osteoclast-like giant cells and lymphoepithelioma-like carcinoma of the stomach: two of a kind? Histopathology. 2005; 47:331–3.
Article
86. Woo HY, Bae YS, Kim JH, et al. Distinct expression profile of key molecules in crawling-type early gastric carcinoma. Gastric Cancer. 2017; 20:612–9.
Article
87. Okamoto N, Kawachi H, Yoshida T, et al. “Crawling-type” adenocarcinoma of the stomach: a distinct entity preceding poorly differentiated adenocarcinoma. Gastric Cancer. 2013; 16:220–32.
Article
88. Ushiku T, Kunita A, Kuroda R, et al. Oxyntic gland neoplasm of the stomach: expanding the spectrum and proposal of terminology. Mod Pathol. 2020; 33:206–16.
Article
89. Tsuji Y, Ushiku T, Shinozaki T, et al. Risk for lymph node metastasis in Epstein-Barr virus-associated gastric carcinoma with submucosal invasion. Dig Endosc. 2021; 33:592–7.
Article
90. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965; 64:31–49.
91. Park DY, Srivastava A, Kim GH, et al. Adenomatous and foveolar gastric dysplasia: distinct patterns of mucin expression and background intestinal metaplasia. Am J Surg Pathol. 2008; 32:524–33.
Article
92. Choi WT, Brown I, Ushiku T, et al. Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases. Histopathology. 2018; 72:1007–14.
Article
93. Kim JM, Sohn JH, Cho MY, et al. Inter-observer reproducibility in the pathologic diagnosis of gastric intraepithelial neoplasia and early carcinoma in endoscopic submucosal dissection specimens: a multi-center study. Cancer Res Treat. 2019; 51:1568–77.
Article
94. Kim JM, Cho MY, Sohn JH, et al. Diagnosis of gastric epithelial neoplasia: dilemma for Korean pathologists. World J Gastroenterol. 2011; 17:2602–10.
Article
95. Watanabe Y, Shimizu M, Itoh T, Nagashima K. Intraglandular necrotic debris in gastric biopsy and surgical specimens. Ann Diagn Pathol. 2001; 5:141–7.
Article
96. Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018; 378:1085–95.
Article
97. Ono H, Yao K, Fujishiro M, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition). Dig Endosc. 2021; 33:4–20.
Article
98. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020; 382:2419–30.
Article
99. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas [Internet]. Silver Spring: U.S. Food and Drug Administration;2021. [cited 2022 Dec 1]. Available from: https://www.fda.gov/drugs/resources-information-approveddrugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-positive-gastric-adenocarcinomas.
100. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20:167–92.
101. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008; 52:797–805.
Article
102. Ahn S, Ahn S, Van Vrancken M, et al. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens. Oncotarget. 2015; 6:38372–80.
Article
103. Lee HS, Kim WH, Kwak Y, et al. Molecular testing for gastrointestinal cancer. J Pathol Transl Med. 2017; 51:103–21.
Article
104. Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017; 35:446–64.
105. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013; 31:3997–4013.
Article
106. Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015; 18:476–84.
Article
107. Tsapralis D, Panayiotides I, Peros G, Liakakos T, Karamitopoulou E. Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology. World J Gastroenterol. 2012; 18:150–5.
Article
108. Liu W, Zhong S, Chen J, Yu Y. HER-2/neu overexpression is an independent prognostic factor for intestinal-type and early-stage gastric cancer patients. Journal of clinical gastroenterology. 2012; 46:e31–7.
Article
109. Lee HE, Park KU, Yoo SB, et al. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. European Journal of Cancer. 2013; 49:1448–57.
Article
110. Kim MA, Lee HJ, Yang HK, Bang YJ, Kim WH. Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma. Histopathology. 2011; 59:822–31.
Article
111. Peng Z, Zou J, Zhang X, et al. HER2 discordance between paired primary gastric cancer and metastasis: a meta-analysis. Chin J Cancer Res. 2015; 27:163–71.
112. Kim JH, Kim MA, Lee HS, Kim WH. Comparative analysis of protein expressions in primary and metastatic gastric carcinomas. Hum Pathol. 2009; 40:314–22.
Article
113. Fusco N, Rocco EG, Del Conte C, et al. HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions. Mod Pathol. 2013; 26:816–24.
Article
114. Geng Y, Chen X, Qiu J, et al. Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer. Int J Clin Oncol. 2014; 19:303–11.
Article
115. Kochi M, Fujii M, Masuda S, et al. Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes. Diagn Pathol. 2013; 8:191.
Article
116. Ieni A, Barresi V, Rigoli L, Caruso RA, Tuccari G. HER2 status in premalignant, early, and advanced neoplastic lesions of the stomach. Dis Markers. 2015; 2015:234851.
Article
117. Zhao W, Sun L, Dong G, Wang X, Jia Y, Tong Z. Receptor conversion impacts outcomes of different molecular subtypes of primary breast cancer. Ther Adv Med Oncol. 2021; 13:17588359211012982.
Article
118. Garrido-Ramos MA. Satellite DNA: an evolving topic. Genes (Basel). 2017; 8:230.
Article
119. Luchini C, Bibeau F, Ligtenberg MJL, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019; 30:1232–43.
Article
120. Li K, Luo H, Huang L, Luo H, Zhu X. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020; 20:16.
Article
121. Jiricny J. Postreplicative mismatch repair. Cold Spring Harb Perspect Biol. 2013; 5:a012633.
Article
122. Ma J, Setton J, Lee NY, Riaz N, Powell SN. The therapeutic significance of mutational signatures from DNA repair deficiency in cancer. Nat Commun. 2018; 9:3292.
Article
123. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003; 21:1174–9.
Article
124. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513:202–9.
125. Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21:449–56.
Article
126. Setia N, Agoston AT, Han HS, et al. A protein and mRNA expression-based classification of gastric cancer. Mod Pathol. 2016; 29:772–84.
Article
127. Ahn S, Lee SJ, Kim Y, et al. High-throughput protein and mRNA expression-based classification of gastric cancers can identify clinically distinct subtypes, concordant with recent molecular classifications. Am J Surg Pathol. 2017; 41:106–15.
Article
128. Choi YY, Kim H, Shin SJ, et al. Microsatellite instability and programmed cell death-ligand 1 expression in stage II/III gastric cancer: post hoc analysis of the CLASSIC randomized controlled study. Ann Surg. 2019; 270:309–16.
129. Guastadisegni C, Colafranceschi M, Ottini L, Dogliotti E. Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data. Eur J Cancer. 2010; 46:2788–98.
Article
130. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018; 24:1449–58.
Article
131. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372:2509–20.
Article
132. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357:409–13.
133. Ratti M, Lampis A, Hahne JC, Passalacqua R, Valeri N. Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci. 2018; 75:4151–62.
Article
134. Jang M, Kwon Y, Kim H, et al. Microsatellite instability test using peptide nucleic acid probe-mediated melting point analysis: a comparison study. Bmc Cancer. 2018; 18:1218.
Article
135. Murphy KM, Zhang S, Geiger T, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006; 8:305–11.
Article
136. Berg KD, Glaser CL, Thompson RE, Hamilton SR, Griffin CA, Eshleman JR. Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction. J Mol Diagn. 2000; 2:20–8.
Article
137. Deschoolmeester V, Baay M, Wuyts W, et al. Detection of microsatellite instability in colorectal cancer using an alternative multiplex assay of quasi-monomorphic mononucleotide markers. J Mol Diagn. 2008; 10:154–9.
Article
138. Shia J, Ellis NA, Klimstra DS. The utility of immunohistochemical detection of DNA mismatch repair gene proteins. Virchows Arch. 2004; 445:431–41.
Article
139. McCarthy AJ, Capo-Chichi JM, Spence T, et al. Heterogenous loss of mismatch repair (MMR) protein expression: a challenge for immunohistochemical interpretation and microsatellite instability (MSI) evaluation. J Pathol Clin Res. 2019; 5:115–29.
Article
140. Renkonen E, Zhang Y, Lohi H, et al. Altered expression of MLH1, MSH2, and MSH6 in predisposition to hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2003; 21:3629–37.
141. Graham RP, Kerr SE, Butz ML, et al. Heterogenous MSH6 loss is a result of microsatellite instability within MSH6 and occurs in sporadic and hereditary colorectal and endometrial carcinomas. Am J Surg Pathol. 2015; 39:1370–6.
Article
142. Jansson A, Arbman G, Zhang H, Sun XF. Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer. Int J Oncol. 2003; 22:41–9.
Article
143. Ruszkiewicz A, Bennett G, Moore J, et al. Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours. Pathology. 2002; 34:541–7.
Article
144. Fukayama M, Abe H, Kunita A, et al. Thirty years of Epstein-Barr virus-associated gastric carcinoma. Virchows Arch. 2020; 476:353–65.
Article
145. Chang MS, Kim DH, Roh JK, et al. Epstein-Barr virus-encoded BARF1 promotes proliferation of gastric carcinoma cells through regulation of NF-kappaB. J Virol. 2013; 87:10515–23.
Article
146. Hoebe EK, Le Large TY, Greijer AE, Middeldorp JM. BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator. Rev Med Virol. 2013; 23:367–83.
Article
147. zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ, van den Brule AJ. Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Res. 2000; 60:2745–8.
148. Kang GH, Lee S, Kim WH, et al. Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotypepositive gastric carcinoma. Am J Pathol. 2002; 160:787–94.
Article
149. Strong MJ, Xu G, Coco J, et al. Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity: implications for possible immune adjuvant therapy. PLoS Pathog. 2013; 9:e1003341.
Article
150. Gu L, Chen M, Guo D, et al. PD-L1 and gastric cancer prognosis: a systematic review and meta-analysis. PLoS One. 2017; 12:e0182692.
Article
151. Park JH, Kim EK, Kim YH, et al. Epstein-Barr virus positivity, not mismatch repair-deficiency, is a favorable risk factor for lymph node metastasis in submucosa-invasive early gastric cancer. Gastric Cancer. 2016; 19:1041–51.
Article
152. Cheng Y, Zhou X, Xu K, Huang J, Huang Q. Very low risk of lymph node metastasis in Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma. BMC Gastroenterol. 2020; 20:273.
Article
153. Yoon CJ, Chang MS, Kim DH, et al. Epstein-Barr virus-encoded miR-BART5-5p upregulates PD-L1 through PIAS3/pSTAT3 modulation, worsening clinical outcomes of PD-L1-positive gastric carcinomas. Gastric Cancer. 2020; 23:780–95.
Article
154. Lee HS, Chang MS, Yang HK, Lee BL, Kim WH. Epstein-barr virus-positive gastric carcinoma has a distinct protein expression profile in comparison with epstein-barr virus-negative carcinoma. Clin Cancer Res. 2004; 10:1698–705.
Article
155. Longnecker RM, Kieff E, Cohen JI. Esptein-Barr virus. In : Knipe DM, Howley PM, editors. Fields virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins;2013. p. 1898–959.
156. Boger C, Kruger S, Behrens HM, et al. Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations. Ann Oncol. 2017; 28:1005–14.
Article
157. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012; 366:2517–9.
Article
158. Kwak Y, Seo AN, Lee HE, Lee HS. Tumor immune response and immunotherapy in gastric cancer. J Pathol Transl Med. 2020; 54:20–33.
Article
159. Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018; 4:e180013.
160. Shitara K, Ozguroglu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018; 392:123–33.
161. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021; 398:27–40.
Article
162. DAKO Agilent Technologies. Interpretation manual: gastric or gastroesophageal junction adenocarcinoma. PD-L1 IHC 22C3 pharmDx interpretation manual: gastric or gastroesophageal juction adenocarcinoma. Santa Clara: DAKO Agilent Technologies;2018.
163. Yang JH, Kim H, Roh SY, et al. Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer. Gastric Cancer. 2019; 22:147–54.
Article
164. Zhou KI, Peterson B, Serritella A, et al. Spatial and temporal heterogeneity of PD-L1 expression and tumor mutational burden in gastroesophageal adenocarcinoma at baseline diagnosis and after chemotherapy. Clin Cancer Res. 2020; 26:6453–63.
Article
165. Son SM, Woo CG, Kim DH, et al. Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients. Sci Rep. 2020; 10:14293.
Article
166. Marchio C, Scaltriti M, Ladanyi M, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol. 2019; 30:1417–27.
Article
167. Catenacci DV, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol. 2020; 38:2418–26.
Article
168. Maron SB, Alpert L, Kwak HA, et al. Targeted therapies for targeted populations: anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma. Cancer Discov. 2018; 8:696–713.
Article
169. Lee J, Kim ST, Kim K, et al. Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY Umbrella Trial. Cancer Discov. 2019; 9:1388–405.
Article
170. Smyth EC, Cafferkey C, Loehr A, et al. Genomic loss of heterozygosity and survival in the REAL3 trial. Oncotarget. 2018; 9:36654–65.
Article
171. Nakamura Y, Kawazoe A, Lordick F, Janjigian YY, Shitara K. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. Nat Rev Clin Oncol. 2021; 18:473–87.
Article
172. van Grieken NC, Aoyama T, Chambers PA, et al. KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer. 2013; 108:1495–501.
Article
173. Wen Z, Xiong D, Zhang S, et al. Case report: RAB10-ALK: a novel ALK fusion in a patient with gastric cancer. Front Oncol. 2021; 11:645370.
Article
174. Lee J, Lee SE, Kang SY, et al. Identification of ROS1 rearrangement in gastric adenocarcinoma. Cancer. 2013; 119:1627–35.
Article
175. Fancello L, Gandini S, Pelicci PG, Mazzarella L. Tumor mutational burden quantification from targeted gene panels: major advancements and challenges. J Immunother Cancer. 2019; 7:183.
Article
176. Lee KW, Van Cutsem E, Bang YJ, et al. Association of tumor mutational burden with efficacy of pembrolizumab+/-chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res. 2022; 28:3489–98.
Article
177. Kang SY, Kim DG, Ahn S, Ha SY, Jang KT, Kim KM. Comparative analysis of microsatellite instability by next-generation sequencing, MSI PCR and MMR immunohistochemistry in 1942 solid cancers. Pathol Res Pract. 2022; 233:153874.
Article
178. Ratovomanana T, Cohen R, Svrcek M, et al. Performance of nextgeneration sequencing for the detection of microsatellite instability in colorectal cancer with deficient DNA mismatch repair. Gastroenterology. 2021; 161:814–26.
Article
179. Ascierto PA, Bifulco C, Palmieri G, Peters S, Sidiropoulos N. Preanalytic variables and tissue stewardship for reliable next-generation sequencing (NGS) clinical analysis. J Mol Diagn. 2019; 21:756–67.
Article
180. Koh J, Lee KW, Nam SK, et al. Development and validation of an easy-to-implement, practical algorithm for the identification of molecular subtypes of gastric cancer: prognostic and therapeutic implications. Oncologist. 2019; 24:e1321–30.
Article
181. Ramos M, Pereira MA, Amorim LC, et al. Gastric cancer molecular classification and adjuvant therapy: is there a different benefit according to the subtype? J Surg Oncol. 2020; 121:804–13.
Article
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