Annals of Surgical Oncology

, Volume 20, Issue 11, pp 3407–3413 | Cite as

Prognostic Value of Mucinous Histology Depends on Microsatellite Instability Status in Patients with Stage III Colon Cancer Treated with Adjuvant FOLFOX Chemotherapy: A Retrospective Cohort Study

  • Se Hyun Kim
  • Sang Joon Shin
  • Kang Young Lee
  • Hyunki Kim
  • Tae Il Kim
  • Dae Ryong Kang
  • Hyuk Hur
  • Byung So Min
  • Nam Kyu Kim
  • Hyun Chul Chung
  • Jae Kyung Roh
  • Joong Bae AhnEmail author
Colorectal Cancer



The close association between mucinous histology and microsatellite instability (MSI) may have hindered the evaluation of prognostic significance of mucinous histology. The aim of this retrospective study was to investigate whether mucinous histology was associated with a worse prognosis, independent of MSI status, compared to nonmucinous histology in patients with stage III colon cancer.


This study enrolled 394 consecutive patients with stage III colorectal cancer treated with adjuvant FOLFOX after curative resection (R0). Clinicopathological information was retrospectively reviewed. Tumors were analyzed for MSI by polymerase chain reaction to determine MSI status. Kaplan–Meier method, log-rank test, and Cox proportional hazard regression models were used.


The estimated rate of 3-year disease-free survival (DFS) in patients with nonmucinous adenocarcinoma (NMA 79.2 %) was significantly greater than that in patients with mucinous adenocarcinoma (MA) and adenocarcinoma with mucinous component (MC) (56.9 %; log-rank, P = 0.002). In univariate analysis, histology (NMA vs. MA/MC), American Joint Committee on Cancer stage (IIIA, IIIB, and IIIC), and lymphovascular invasion (present vs. absent) were significantly associated with DFS. In multivariate analysis, mucinous histology (MA/MC) was associated with decreased DFS in all patients (hazard ratio 1.82, 95 % confidence interval 1.03–3.23, P = 0.0403). In patients with MA/MC, no difference in DFS was observed between MSI and microsatellite stability (log-rank, P = 0.732).


Mucinous histology is an independent poor prognostic factor for DFS in patients with stage III colon cancer after adjuvant FOLFOX chemotherapy.


Colon Cancer Lymphovascular Invasion Mucinous Adenocarcinoma Severance Hospital Independent Poor Prognostic Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have nothing to disclose.

Supplementary material

10434_2013_3169_MOESM1_ESM.tif (3.2 mb)
Supplementary Fig. 2 Disease-free survival for patients with mucinous and non-mucinous colon cancer according to MSI status (TIF 3230 kb)


  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Verhulst J, Ferdinande L, Demetter P, Ceelen W. Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis. J Clin Pathol. 2012;65:381–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. 3rd edition. Lyon: IARC; 2000.Google Scholar
  4. 4.
    Nissan A, Guillem JG, Paty PB, Wong WD, Cohen AM. Signet-ring cell carcinoma of the colon and rectum: a matched control study. Dis Colon Rectum. 1999;42:1176–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Kang H, O’Connell JB, Maggard MA, Sack J, Ko CY. A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum. 2005;48:1161–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists consensus statement, 1999. Arch Pathol Lab Med. 2000;124:979–94.PubMedGoogle Scholar
  7. 7.
    Ogino S, Brahmandam M, Cantor M, et al. Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Mod Pathol. 2006;19:59–68.PubMedCrossRefGoogle Scholar
  8. 8.
    Song GA, Deng G, Bell I, Kakar S, Sleisenger MH, Kim YS. Mucinous carcinomas of the colorectum have distinct molecular genetic characteristics. Int J Oncol. 2005;26:745–50.PubMedGoogle Scholar
  9. 9.
    Tanaka H, Deng G, Matsuzaki K, et al. BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer. Int J Cancer. 2006;118:2765–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Negri FV, Wotherspoon A, Cunningham D, Norman AR, Chong G, Ross PJ. Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer. Ann Oncol. 2005;16:1305–10.PubMedCrossRefGoogle Scholar
  12. 12.
    Catalano V, Loupakis F, Graziano F, et al. Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer. 2009;100:881–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Kanemitsu Y, Kato T, Hirai T, et al. Survival after curative resection for mucinous adenocarcinoma of the colorectum. Dis Colon Rectum. 2003;46:160–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Hyngstrom JR, Hu CY, Xing Y, et al. Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol. 2012;19:2814–21.PubMedCrossRefGoogle Scholar
  15. 15.
    Catalano V, Loupakis F, Graziano F, et al. Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer. Ann Oncol. 2012;23:135–41.PubMedCrossRefGoogle Scholar
  16. 16.
    Consorti F, Lorenzotti A, Midiri G, Di Paola M. Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol. 2000;73:70–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.PubMedCrossRefGoogle Scholar
  18. 18.
    Bertagnolli MM, Redston M, Compton CC, et al. Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer—a study of CALGB 9581 and 89803. J Clin Oncol. 2011;29:3153–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Boland CR, Thibodeau SN, Hamilton SR, 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;58:5248–57.PubMedGoogle Scholar
  20. 20.
    Laiho P, Launonen V, Lahermo P, et al. Low-level microsatellite instability in most colorectal carcinomas. Cancer Res. 2002;62:1166–70.PubMedGoogle Scholar
  21. 21.
    Sargent DJ, Wieand HS, Haller DG, et al. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2005;23:8664–70.PubMedCrossRefGoogle Scholar
  22. 22.
    Lin CC, Lin JK, Chang SC, et al. Is adjuvant chemotherapy beneficial to high risk stage II colon cancer? Analysis in a single institute. Int J Colorect Dis. 2009;24:665–76.CrossRefGoogle Scholar
  23. 23.
    Kondo T, Masuda H, Abe Y, Takayama T. Two subtypes in colorectal mucinous carcinoma in relation to microsatellite instability. Hepatogastroenterology. 2002;49:660–3.PubMedGoogle Scholar
  24. 24.
    Liu XP, Sato T, Oga A, Ikemoto K, Kawauchi S, Ikeda E, Sasaki K. Two subtypes of mucinous colorectal carcinoma characterized by laser scanning cytometry and comparative genomic hybridization. Int J Oncol. 2004;25:615–21.PubMedGoogle Scholar
  25. 25.
    Leopoldo S, Lorena B, Cinzia A, et al. Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features. Ann Surg Oncol. 2008;15:1429–39.PubMedCrossRefGoogle Scholar
  26. 26.
    Shen L, Catalano PJ, Benson AB III, O’Dwyer P, Hamilton SR, Issa JPJ. Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil-based chemotherapy. Clin Cancer Res. 2007;13:6093–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Jover R, Nguyen TP, Pérez-Carbonell L, et al. 5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology. 2011;140:1174–81.PubMedCrossRefGoogle Scholar
  28. 28.
    Langner C, Harbaum L, Pollheimer MJ, et al. Mucinous differentiation in colorectal cancer—indicator of poor prognosis? Histopathology. 2012;60:1060–72.PubMedCrossRefGoogle Scholar
  29. 29.
    Han-Shiang C. Curative resection of colorectal adenocarcinoma: multivariate analysis of 5-year follow-up. World J Surg. 1999;23:1301–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Chew MH, Koh PK, Ng KH, Eu KW. Improved survival in an Asian cohort of young colorectal cancer patients: an analysis of 523 patients from a single institution. Int J Colorect Dis. 2009;24:1075–83.CrossRefGoogle Scholar
  31. 31.
    Halvorsen T, Seim E. Influence of mucinous components on survival in colorectal adenocarcinomas: a multivariate analysis. J Clin Pathol. 1988;41:1068–72.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Se Hyun Kim
    • 1
  • Sang Joon Shin
    • 1
  • Kang Young Lee
    • 2
  • Hyunki Kim
    • 3
  • Tae Il Kim
    • 1
  • Dae Ryong Kang
    • 4
  • Hyuk Hur
    • 2
  • Byung So Min
    • 2
  • Nam Kyu Kim
    • 2
  • Hyun Chul Chung
    • 1
  • Jae Kyung Roh
    • 1
  • Joong Bae Ahn
    • 1
    • 5
    Email author
  1. 1.Department of Internal MedicineYonsei University College of MedicineSeoulKorea
  2. 2.Department of SurgeryYonsei University College of MedicineSeoulKorea
  3. 3.Department of PathologyYonsei University College of MedicineSeoulKorea
  4. 4.Biostatistics Collaboration UnitYonsei University College of MedicineSeoulKorea
  5. 5.Institute for Cancer ResearchYonsei University College of MedicineSeoulKorea

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