[Roles of beta-catenin overexpression and adenomatous polyposis coli mutation in head and neck cancer].
Beta-catenin is an undercoat protein of cadherin, a cellular adhesion molecule. Beta-catenin also functions as a transcriptional activator downstream of the Wnt signaling pathway. Intracellular beta-catenin is regulated by the formation of a complex with APC (adenomatous polyposis coli) protein. The activation of this pathway by stabilization with beta-catenin has been shown to be an important step in the development of colorectal carcinoma, which is mainly caused by inactivating mutations in the APC tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. This study was conducted to clarify the contribution of beta-catenin accumulation and the mutation of the beta-catenin gene to the carcinogenesis of head and neck cancer. Beta-catenin accumulation was examined immunohistochemically in 49 frozen or formalin-fixed, paraffin-embedded samples of head and neck tumors. We also performed a direct sequence analysis of APC and beta-catenin to examine the cause of beta-catenin accumulation. Genomic DNA was extracted and purified from fresh tissue samples of head and neck cancers. We examined the APC mutation cluster region in 15 samples and analyzed beta-catenin exon 3 mutations in 31 cases. Twelve out of 49 (24.5%) cases exhibited beta-catenin accumulation in our histochemical study. The 5 year survival rate was 0% in the beta-catenin accumulation group, compared to 50% in the non-accumulation group, (p < 0.01). This finding strongly suggests that beta-catenin may play an important role in the carcinogenesis or progression of head and neck cancer. One of the 15 cases exhibited an APC missense mutation that led to the replacement of amino acids; this case died in 12 months. Regarding the beta-catein mutation, non of the 31 samples exhibited a gene mutation in beta-catenin exon 3. Thus, the rate of APC and beta-catenin mutation in head and neck cancer may be very low.
Takei
Shin
S
Department of Otolaryngology-Head and Neck Surgery, Wakayama Medical College, Wakayama.
Ueno
Yumi
Y
Yoda
Junichi
J
Tamura
Shinji
S
Hotomi
Muneki
M
Fujihara
Keiji
K
Kuki
Kiyonori
K
Yamanaka
Noboru
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017491:Genes, APC; D006258:Head and Neck Neoplasms / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin