Expression of transcription factor AP-2 in colorectal adenomas and adenocarcinomas; comparison of immunohistochemistry and in situ hybridisation

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Abstract
Aims—To investigate whether the three different AP-2 isoforms are expressed differently in colorectal adenomas and carcinomas. Methods—The study comprised 43 randomly selected patients diagnosed and treated at Kuopio University Hospital in 1996 for colorectal adenocarcinoma (n = 30) and colorectal adenoma (n = 13). The expression of AP-2α, AP-2β, and AP-2γ was analysed by immunohistochemistry (IHC) and the mRNA status of AP-2α was determined by in situ hybridisation (ISH) and confirmed by reverse transcription polymerase chain reaction (RT-PCR). AP-2 expression patterns were correlated with clinicopathological variables. Results—In adenomas and carcinomas, AP-2β cytoplasmic positivity was higher than that of AP-2α or AP-2γ. AP-2α expression was reduced in advanced Dukes's stage carcinomas. In high grade carcinomas, both AP-2α and AP-2γ expression was reduced. ISH demonstrated increased AP-2α values in high grade carcinomas. Seven of 30 carcinoma specimens displayed a moderate or strong mRNA signal, despite being negative for AP-2α protein. RT-PCR from AP-2α mRNA and protein positive tumours confirmed that the positive signal in ISH originated from the exon 2 of TFAP2A. Conclusions—AP-2α was reduced in advanced Dukes's stage adenocarcinomas. Together with reduced AP-2γ expression in high grade carcinomas, this might contribute to tumour progression. The discrepancy between mRNA and protein expression suggests that post-transcriptional regulatory mechanisms might modify the availability of functional AP-2α protein in colorectal carcinoma.