Distinct secreted Frizzled receptor protein 1 staining pattern in patients with hyperplastic polyposis coli syndrome.

Context: Patients with hyperplastic polyposis coli syndrome are thought to harbor precursor lesions of a proposed hyperplasia-carcinoma pathway in colorectal cancer, but morphologic recognition of such lesions remains difficult. Hypermethylation of the secreted Frizzled receptor protein 1 gene on chromosome 8p12 is one of the earliest molecular alterations in colorectal carcinogenesis, potentially disrupting the Wnt signaling cascade of cellular growth control.

Objective: To determine if hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a distinct immunohistochemical expression pattern for mismatch repair proteins and secreted Frizzled receptor protein 1 compared to their sporadic counterparts.

Design: Immunohistochemical studies (secreted Frizzled receptor protein 1, 3 mismatch repair proteins, and p53) were performed on 23 hyperplastic polyps, 6 synchronous colon cancers, and normal colonic mucosa from 6 patients with hyperplastic polyposis coli syndrome and were compared with studies of sporadic hyperplastic polyps obtained from 13 matched control subjects.

Results: The staining pattern for the mismatch repair proteins MLH-1, MSH-2, and MSH-6 did not differ between sporadic and syndromic hyperplastic polyps. In contrast, 52% of syndromic hyperplastic polyps showed a reproducible and distinct staining pattern for secreted Frizzled receptor protein 1 that was not seen in control specimens and that was associated with larger polyp size (P =.002) and location in the proximal colon (P =.01).

Conclusions: Some hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a secreted Frizzled receptor protein 1 immunophenotype that could indicate alterations of cellular growth control. These findings may help identify precursor lesions in the proposed hyperplasia-carcinoma pathway of colorectal carcinogenesis.