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

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 tre ated at Kuopio University Hospital in 1996 for colorectal adenocarcinoma (n = 30) and colorectal adenoma (n = 13). The expression of AT-2 alpha, AP-2 beta, and AP-2 gamma was analysed by immunohistochemistry (IHC) and the mRN A status of AP-2 alpha was determined by in situ hybridisation (ISH) and co nfirmed by reverse transcription polymerase chain reaction (RT-PCR). AP-2 e xpression patterns were correlated with clinicopathological variables. Results-In adenomas and carcinomas, AP-2 beta cytoplasmic positivity was hi gher than that of AP-2 alpha or AP-2 gamma. AP-2 alpha expression was reduc ed in advanced Dukes's stage carcinomas. In high grade carcinomas, both AP- 2 alpha and AP-2 gamma expression was reduced. ISH demonstrated increased A P-2 alpha values in high grade carcinomas. Seven of 30 carcinoma specimens displayed a moderate or strong mRNA signal, despite being negative for AP-2 alpha protein. RT-PCR from AP-2 alpha mRNA and protein positive tumours co nfirmed that the positive signal in ISH originated from the exon 2 of TFAP2 A. Conclusions-AP-2 alpha was reduced in advanced Dukes's stage adenocarcinoma s. Together with reduced AP-2 gamma expression in high grade carcinomas, th is might contribute to tumour progression. The discrepancy between mRNA and protein expression suggests that post-transcriptional regulatory mechanism s might modify the availability of functional AP-2 alpha protein in colorec tal carcinoma.