Expression of transcription factor AP-2 in colorectal adenomas and adenocarcinomas; comparison of immunohistochemistry and in situ hybridisation.
OBJECTIVE
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-2alpha, AP-2beta, and AP-2gamma was analysed by immunohistochemistry (IHC) and the mRNA status of AP-2alpha 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-2beta cytoplasmic positivity was higher than that of AP-2alpha or AP-2gamma. AP-2alpha expression was reduced in advanced Dukes's stage carcinomas. In high grade carcinomas, both AP-2alpha and AP-2gamma expression was reduced. ISH demonstrated increased AP-2alpha values in high grade carcinomas. Seven of 30 carcinoma specimens displayed a moderate or strong mRNA signal, despite being negative for AP-2alpha protein. RT-PCR from AP-2alpha mRNA and protein positive tumours confirmed that the positive signal in ISH originated from the exon 2 of TFAP2A.


CONCLUSIONS
AP-2alpha was reduced in advanced Dukes's stage adenocarcinomas. Together with reduced AP-2gamma 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-2alpha protein in colorectal carcinoma.
Ropponen
K M
KM
Department of Pathology and Forensic Medicine, University of Kuopio, PO Box 1627, FIN 70211, Kuopio University Hospital, Kuopio, Finland.
Kellokoski
J K
JK
Pirinen
R T
RT
Moisio
K I
KI
Eskelinen
M J
MJ
Alhava
E M
EM
Kosma
V M
VM
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C493673:TFAP2A protein, human; C493677:TFAP2B protein, human; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors