Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features

Ann Surg Oncol. 2008 May;15(5):1429-39. doi: 10.1245/s10434-007-9757-1. Epub 2008 Feb 27.

Abstract

Background: This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent.

Methods: One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes.

Results: MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) phenotype, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02).

Conclusion: The results of the present study confirm that MUC represents distinct clinicopathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Aged
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Loss of Heterozygosity
  • Male
  • Microsatellite Instability*
  • Microsatellite Repeats / genetics*
  • Mucin-1 / genetics*
  • Neoplasm Recurrence, Local / diagnosis
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MUC1 protein, human
  • Mucin-1