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Inverse Effects of Mucin on Survival of Matched Hereditary Nonpolyposis Colorectal Cancer and Sporadic Colorectal Cancer Patients

Authors' Affiliations: ¹ Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine at Linko; ² Department of Public Health and ³ Division of Cancer Research, National Health Research Institute; and ⁴ Graduate Institute of Basic Medical Science, Chang Gung University, Taipei, Taiwan

Requests for reprints: Reiping Tang, Colorectal Section, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, Taiwan. Phone: 886-3-3281200 ext. 3225; Fax: 886-3-3278355; E-mail: rptang{at}adm.cgmh.org.tw.

Purpose: To compare survival and histologic features of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) cases to well-matched sporadic colon cancers from the same patient population.

Experimental Design: Between January 1995 and March 2002, a total of 5,138 consecutive patients underwent resection of primary colorectal adenocarcinoma in a single institution. According to the Amsterdam criteria, 56 HNPCC patients were matched to 147 sporadic colorectal cancer (SCRC) with no family history of cancer and with the same gender, tumor location, and age within 3 years. Immunohistochemical analyses were done for MUC1, MUC2, MUC3, and MUC5AC.

Results: The HNPCC group had a marginally significantly better long-term outcome than the SCRC group (P = 0.058). The trend disappeared after adjustment by tumor-node-metastasis stage in a Cox model (P = 0.774). We noted a difference of >50% in the 5-year cancer-specific survival rates of HNPCC- and SCRC-mucinous groups (92% versus 31%, P = 0.0003). Interaction between mucin and HNPCC and its effects on survival were further confirmed by comparing the Cox models with and without interaction terms (hazard ratio, 0.1; P = 0.034 with adjusting stage). Patients with tumors showing dual expression of mucin and MUC1, which appeared in 11% of those with HNPCC and 50% of those with SCRC, had a lower 5-year cancer-specific survival rate than patients without (30% versus 60%; P = 0.004 by log-rank test; P = 0.039 with adjustment for tumor-node-metastasis stage).

Conclusions: These results suggest that mucin has an inverse effect on survival in patients with HNPCC and SCRC, which might be partly explained by a lower prevalence of MUC1 expression in the mucinous HNPCC group than in the SCRC groups.