APC and beta-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers.
OBJECTIVE
The adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) genes are the two major components of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. The overactivation of the pathway, which results in abnormal accumulation of beta-catenin protein in nuclei, contributes to most colorectal cancers (CRCs), both sporadic and hereditary, as well as sporadic endometrial cancers (ECs). Here, we studied the involvement of APC and beta-catenin in hereditary nonpolyposis colorectal cancer (HNPCC)-related ECs, and compared the expression patterns to those in HNPCC-related CRCs.


METHODS
Nineteen ECs and 31 CRCs derived from HNPCC patients were immunohistochemically stained with anti-APC- and anti-beta-catenin-antibodies.


RESULTS
Tumor-specific loss of APC was observed in 16 of endometrial cancers (3 of 19) and in 39 of colorectal cancers (12 of 31). Consistently, the loss of APC expression was associated with nuclear beta-catenin staining. Altogether, aberrant beta-catenin localization was observed in 53 of ECs (10 of 19) as compared to 84 of CRCs (26 of 31) (P=0.02).


CONCLUSIONS
Our results suggest a frequent overactivation of the Wnt signaling pathway in hereditary endometrial cancer. In accordance with studies on sporadic cancers, abnormal accumulation of beta-catenin protein in nuclei occurred much less frequently in HNPCC-related ECs than CRCs, which may reflect organ-specific differences in their pathogenesis.
Kariola
Reetta
R
Department of Biological and Environmental Sciences, Genetics, University of Helsinki, Viikinkaari 5, 00014 Helsinki, Finland.
Abdel-Rahman
Wael M
WM
Ollikainen
Miina
M
Butzow
Ralf
R
Peltomäki
Päivi
P
Nyström
Minna
M
D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008297:Male; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*; D051153:Wnt Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin