Cancer Res Treat.  2008 Jun;40(2):75-80.

Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer

• Park SJ
• Lee KY
• Kim SY

Abstract

PURPOSE: A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer.
MATERIALS AND METHODS
The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival.
RESULTS
Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis.
CONCLUSIONS
Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.

Keyword

Colonic neoplasms; Lymphatic metastasis; Immunohistochemistry; Survival

MeSH Terms

Colon
Colonic Neoplasms
Eosine Yellowish-(YS)
Follow-Up Studies
Hematoxylin
Humans
Immunohistochemistry
Lymph Nodes
Lymphatic Metastasis
Multivariate Analysis
Neoplasm Metastasis
Neoplasm Micrometastasis
Rectal Neoplasms
Recurrence
Eosine Yellowish-(YS)
Hematoxylin

Figure

• 

  Fig. 1 Disease-free survival according to (A) the stage (stage I vs. stage II) and (B) the number of retrieved LNs (<12 vs. ≥12). Both parameters were found to be significantly associated with disease-free survival.

• 

  Fig. 2 Overall survival according to (A) the number of retrieved LNs (<12 vs. ≥12) and (B) lymphatic invasion (absent vs. present). Both parameters were found to be significantly associated with disease-free survival.

Reference

1. Park JG. Cancer Incidence in Korea 1999~2001. 2005. Goyang: National Cancer Center.

2. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007; 57:43–66. PMID: 17237035.

3. Chen SL, Bilchik AJ. More extensive nodal dissection improves survival for stages I to III of colon cancer: a population-based study. Ann Surg. 2006; 244:602–610. PMID: 16998369.

4. Adell G, Boeryd B, Franlund B, Sjodahl R, Hakansson L. Occurrence and prognostic importance of micrometastases in regional lymph nodes in Duke's B colorectal carcinoma: an immunohistochemical study. Eur J Surg. 1996; 162:637–642. PMID: 8891622.

5. Choi HJ, Choi YY, Hong SH. Incidence and prognostic implications of isolated tumor cells in lymph nodes from patients with Dukes B colorectal carcinoma. Dis Colon Rectum. 2002; 45:750–755. PMID: 12072625.

6. Davidson BR, Sams VR, Styles J, Deane C, Boulos PB. Detection of occult nodal metastases in patients with colorectal carcinoma. Cancer. 1990; 65:967–970. PMID: 2297665.

7. Greenson JK, Isenhart CE, Rice R, Mojzisik C, Houchens D, Martin EW Jr. Identification of occult micrometastases in pericolic lymph nodes of Duke's B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival. Cancer. 1994; 73:563–569. PMID: 7507795.

8. Isaka N, Nozue M, Doy M, Fukao K. Prognostic significance of perirectal lymph node micrometastases in Duke's B rectal carcinoma: an immunohistochemical study by CAM5.2. Clin Cancer Res. 1999; 5:2065–2068. PMID: 10473087.

9. Kronberg U, Lopez-Kostner F, Soto G, Zuniga A, Wistuba I, Miranda V, et al. Detection of lymphatic micrometastases in patients with stages I and II colorectal cancer: impact on five-year survival. Dis Colon Rectum. 2004; 47:1151–1157. PMID: 15164250.

10. Nakanishi Y, Ochiai A, Yamauchi Y, Moriya Y, Yoshimura K, Hirohashi S. Clinical implications of lymph node micrometastases in patients with colorectal cancers. A case control study. Oncology. 1999; 57:276–280. PMID: 10575311.

11. Noura S, Yamamoto H, Miyake Y, Kim B, Takayama O, Seshimo I, et al. Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer. Clin Cancer Res. 2002; 8:759–767. PMID: 11895906.

12. Rosenberg R, Friederichs J, Gertler R, Hoos A, Mueller J, Nahrig J, et al. Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer. Int J Colorectal Dis. 2004; 19:430–437. PMID: 14716495.

13. Tschmelitsch J, Klimstra DS, Cohen AM. Lymph node micrometastases do not predict relapse in stage II colon cancer. Ann Surg Oncol. 2000; 7:601–608. PMID: 11005559.

14. Huvos AG, Hutter RV, Berg JW. Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg. 1971; 173:44–46. PMID: 5543548.

15. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, et al. AJCC Cancer Staging Manual. 2002. 6th ed. New York: Springer-Verlag;p. 226–228.

16. O'Brien MJ, Zamcheck N, Burke B, Kirkham SE, Saravis CA, Gottlieb LS. Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues Assessment of diagnostic value. Am J Clin Pathol. 1981; 75:283–290. PMID: 7010989.

17. Sasaki M, Watanabe H, Jass JR, Ajioka Y, Kobayashi M, Matsuda K, et al. Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in "nodenegative" colorectal cancer. J Gastroenterol. 1997; 32:758–764. PMID: 9430013.

18. Yasuda K, Adachi Y, Shiraishi N, Yamaguchi K, Hirabayashi Y, Kitano S. Pattern of lymph node micrometastasis and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2001; 8:300–304. PMID: 11352302.

19. Liefers GJ, Cleton-Jansen AM, van de Velde CJ, Hermans J, van Krieken JH, Cornelisse CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med. 1998; 339:223–228. PMID: 9673300.

20. Noura S, Yamamoto H, Ohnishi T, Masuda N, Matsumoto T, Takayama O, et al. Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol. 2002; 20:4232–4241. PMID: 12377967.

21. Rosenberg R, Hoos A, Mueller J, Baier P, Stricker D, Werner M, et al. Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients. J Clin Oncol. 2002; 20:1049–1055. PMID: 11844829.

22. Bilchik AJ, Hoon DS, Saha S, Turner RR, Wiese D, DiNome M, et al. Prognostic impact of micrometastases in colon cancer: interim results of a prospective multicenter trial. Ann Surg. 2007; 246:568–575. PMID: 17893493.

23. Rodriguez-Bigas MA, Maamoun S, Weber TK, Penetrante RB, Blumenson LE, Petrelli NJ. Clinical significance of colorectal cancer: metastases in lymph nodes <5 mm in size. Ann Surg Oncol. 1996; 3:124–130. PMID: 8646511.

24. Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004; 22:3408–3419. PMID: 15199089.

25. Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. 2001; 93:583–596. PMID: 11309435.