Yonsei Med J.  2015 Jan;56(1):175-181. 10.3349/ymj.2015.56.1.175.

Clinical Implications of Microsatellite Instability in T1 Colorectal Cancer

Affiliations
  • 1Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. kylee117@yuhs.ac

Abstract

PURPOSE
The estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM.
MATERIALS AND METHODS
A total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses.
RESULTS
Among 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS.
CONCLUSION
MSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.

Keyword

Microsatellite instability; lymph node metastasis; early colorectal cancer; T1; prognosis

MeSH Terms

Adult
Aged
Aged, 80 and over
Colorectal Neoplasms/*genetics/*pathology
Female
Humans
Lymph Nodes/pathology
Lymphatic Metastasis/pathology
Male
*Microsatellite Instability
Microsatellite Repeats/genetics
Middle Aged
Neoplasm Staging
Risk Factors
Survival Analysis

Figure

  • Fig. 1 Comparison of survival between MSI-H group and MSI-L/MSS group. There was no difference of survival outcomes between "MSI-H group" and "MSI-L/MSS group" (mean follow-up periods: 31 months). DFS, disease-free survival; MSI-H, high-frequency microsatellite instability; MSI-L, low-frequency microsatellite instability; MSS, microsatellite stable.


Reference

1. Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata H, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004; 39:534–543.
Article
2. Tominaga K, Nakanishi Y, Nimura S, Yoshimura K, Sakai Y, Shimoda T. Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Dis Colon Rectum. 2005; 48:92–100.
Article
3. Yamamoto S, Watanabe M, Hasegawa H, Baba H, Yoshinare K, Shiraishi J, et al. The risk of lymph node metastasis in T1 colorectal carcinoma. Hepatogastroenterology. 2004; 51:998–1000.
4. Nascimbeni R, Burgart LJ, Nivatvongs S, Larson DR. Risk of lymph node metastasis in T1 carcinoma of the colon and rectum. Dis Colon Rectum. 2002; 45:200–206.
Article
5. Minsky BD, Rich T, Recht A, Harvey W, Mies C. Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer. Cancer. 1989; 63:1421–1429.
Article
6. Takano S, Kato J, Yamamoto H, Shiode J, Nasu J, Kawamoto H, et al. Identification of risk factors for lymph node metastasis of colorectal cancer. Hepatogastroenterology. 2007; 54:746–750.
7. Wang H, Wei XZ, Fu CG, Zhao RH, Cao FA. Patterns of lymph node metastasis are different in colon and rectal carcinomas. World J Gastroenterol. 2010; 16:5375–5379.
Article
8. Mou S, Soetikno R, Shimoda T, Rouse R, Kaltenbach T. Pathologic predictive factors for lymph node metastasis in submucosal invasive (T1) colorectal cancer: a systematic review and meta-analysis. Surg Endosc. 2013; 27:2692–2703.
Article
9. Shibata D, Peinado MA, Ionov Y, Malkhosyan S, Perucho M. Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet. 1994; 6:273–281.
Article
10. Yamashita K, Dai T, Dai Y, Yamamoto F, Perucho M. Genetics supersedes epigenetics in colon cancer phenotype. Cancer Cell. 2003; 4:121–131.
Article
11. Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C. The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer. 2003; 3:695–701.
Article
12. Nasu T, Oku Y, Takifuji K, Hotta T, Yokoyama S, Matsuda K, et al. Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression. J Surg Res. 2013; 185:136–142.
Article
13. Chung DC, Rustgi AK. DNA mismatch repair and cancer. Gastroenterology. 1995; 109:1685–1699.
Article
14. Rhyu MS. Molecular mechanisms underlying hereditary nonpolyposis colorectal carcinoma. J Natl Cancer Inst. 1996; 88:240–251.
Article
15. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993; 260:816–819.
Article
16. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998; 58:5248–5257.
17. Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998; 338:1481–1487.
Article
18. Boland CR, Shin SK, Goel A. Promoter methylation in the genesis of gastrointestinal cancer. Yonsei Med J. 2009; 50:309–321.
Article
19. Michel S, Benner A, Tariverdian M, Wentzensen N, Hoefler P, Pommerencke T, et al. High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability. Br J Cancer. 2008; 99:1867–1873.
Article
20. Gafà R, Maestri I, Matteuzzi M, Santini A, Ferretti S, Cavazzini L, et al. Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer. 2000; 89:2025–2037.
Article
21. Liang JT, Huang KC, Cheng AL, Jeng YM, Wu MS, Wang SM. Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age. Br J Surg. 2003; 90:205–214.
Article
22. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000; 342:69–77.
Article
23. Lim SB, Jeong SY, Lee MR, Ku JL, Shin YK, Kim WH, et al. Prognostic significance of microsatellite instability in sporadic colorectal cancer. Int J Colorectal Dis. 2004; 19:533–537.
Article
24. Malesci A, Laghi L, Bianchi P, Delconte G, Randolph A, Torri V, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res. 2007; 13:3831–3839.
Article
25. Loukola A, Eklin K, Laiho P, Salovaara R, Kristo P, Järvinen H, et al. Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res. 2001; 61:4545–4549.
26. Kim H, An JY, Noh SH, Shin SK, Lee YC, Kim H. High microsatellite instability predicts good prognosis in intestinal-type gastric cancers. J Gastroenterol Hepatol. 2011; 26:585–592.
Article
27. Huddy SP, Husband EM, Cook MG, Gibbs NM, Marks CG, Heald RJ. Lymph node metastases in early rectal cancer. Br J Surg. 1993; 80:1457–1458.
Article
28. Tepper JE, O'Connell MJ, Niedzwiecki D, Hollis D, Compton C, Benson AB 3rd, et al. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol. 2001; 19:157–163.
Article
29. Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007; 99:433–441.
Article
30. Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol. 2003; 21:2912–2919.
Article
31. Ogino S, Nosho K, Irahara N, Shima K, Baba Y, Kirkner GJ, et al. Negative lymph node count is associated with survival of colorectal cancer patients, independent of tumoral molecular alterations and lymphocytic reaction. Am J Gastroenterol. 2010; 105:420–433.
Article
32. Belt EJ, te Velde EA, Krijgsman O, Brosens RP, Tijssen M, van Essen HF, et al. High lymph node yield is related to microsatellite instability in colon cancer. Ann Surg Oncol. 2012; 19:1222–1230.
Article
33. MacQuarrie E, Arnason T, Gruchy J, Yan S, Drucker A, Huang WY. Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer. Hum Pathol. 2012; 43:1258–1264.
Article
34. Søreide K, Ogino S. Microsatellite instability and retrieval of lymph nodes in stage III colon cancer: harbinger or hermit. Hum Pathol. 2012; 43:1785–1786.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr