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

K M Ropponen¹, J K Kellokoski^1,3, R T Pirinen¹, K I Moisio¹, M J Eskelinen², E M Alhava², V-M Kosma¹

¹ Department of Pathology and Forensic Medicine, University of Kuopio, PO Box 1627, FIN 70211, Kuopio University Hospital, Kuopio, Finland
² Department of Surgery, University of Kuopio
³ Departments of Oral and Maxillofacial Unit and Oncology, Kuopio University Hospital

Correspondence to:
Dr Kosma VeliMatti.Kosma{at}uku.fi

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

Conclusions—AP-2 was reduced in advanced Dukes's stage adenocarcinomas. Together with reduced AP-2 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-2 protein in colorectal carcinoma.

Key Words: AP-2 proteins • immunohistochemistry • in situ hybridisation • colorectal neoplasms

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Orso, F., Penna, E., Cimino, D., Astanina, E., Maione, F., Valdembri, D., Giraudo, E., Serini, G., Sismondi, P., De Bortoli, M., Taverna, D. (2008). AP-2{alpha} and AP-2{gamma} regulate tumor progression via specific genetic programs. FASEB J. 22: 2702-2714 [Abstract] [Full Text]  
• Choi, H.-J., Chung, T.-W., Kim, S.-J., Cho, S.-Y., Lee, Y.-S., Lee, Y.-C., Ko, J.-H., Kim, C.-H. (2008). The AP-2{alpha} transcription factor is required for the ganglioside GM3-stimulated transcriptional regulation of a PTEN gene. Glycobiology 18: 395-407 [Abstract] [Full Text]  
• Hannay, J. A.F., Liu, J., Zhu, Q.-S., Bolshakov, S. V., Li, L., Pisters, P. W.T., Lazar, A. J.F., Yu, D., Pollock, R. E., Lev, D. (2007). Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation. Molecular Cancer Therapeutics 6: 1650-1660 [Abstract] [Full Text]  
• Lopez-Soto, A., Quinones-Lombrana, A., Lopez-Arbesu, R., Lopez-Larrea, C., Gonzalez, S. (2006). Transcriptional Regulation of ULBP1, a Human Ligand of the NKG2D Receptor. J. Biol. Chem. 281: 30419-30430 [Abstract] [Full Text]  
• Wajapeyee, N., Britto, R., Ravishankar, H. M., Somasundaram, K. (2006). Apoptosis Induction by Activator Protein 2{alpha} Involves Transcriptional Repression of Bcl-2. J. Biol. Chem. 281: 16207-16219 [Abstract] [Full Text]  
• Wang, X., Bolotin, D., Chu, D. H., Polak, L., Williams, T., Fuchs, E. (2006). AP-2{alpha}: a regulator of EGF receptor signaling and proliferation in skin epidermis. JCB 172: 409-421 [Abstract] [Full Text]  
• Wajapeyee, N., Raut, C. G., Somasundaram, K. (2005). Activator Protein 2{alpha} Status Determines the Chemosensitivity of Cancer Cells: Implications in Cancer Chemotherapy. Cancer Res. 65: 8628-8634 [Abstract] [Full Text]  
• Hoei-Hansen, C. E., Nielsen, J. E., Almstrup, K., Sonne, S. B., Graem, N., Skakkebaek, N. E., Leffers, H., Meyts, E. R.-D. (2004). Transcription Factor AP-2{gamma} Is a Developmentally Regulated Marker of Testicular Carcinoma In situ and Germ Cell Tumors. Clin. Cancer Res. 10: 8521-8530 [Abstract] [Full Text]  
• Li, Q., Dashwood, R. H. (2004). Activator Protein 2{alpha} Associates with Adenomatous Polyposis Coli/{beta}-Catenin and Inhibits {beta}-Catenin/T-cell Factor Transcriptional Activity in Colorectal Cancer Cells. J. Biol. Chem. 279: 45669-45675 [Abstract] [Full Text]  
• Wajapeyee, N., Somasundaram, K. (2003). Cell Cycle Arrest and Apoptosis Induction by Activator Protein 2{alpha} (AP-2{alpha}) and the Role of p53 and p21WAF1/CIP1 in AP-2{alpha}-mediated Growth Inhibition. J. Biol. Chem. 278: 52093-52101 [Abstract] [Full Text]  
• McPherson, L. A., Loktev, A. V., Weigel, R. J. (2002). Tumor Suppressor Activity of AP2alpha Mediated through a Direct Interaction with p53. J. Biol. Chem. 277: 45028-45033 [Abstract] [Full Text]  
• Rosivatz, E., Becker, I., Specht, K., Fricke, E., Luber, B., Busch, R., Hofler, H., Becker, K.-F. (2002). Differential Expression of the Epithelial-Mesenchymal Transition Regulators Snail, SIP1, and Twist in Gastric Cancer. Am. J. Pathol. 161: 1881-1891 [Abstract] [Full Text]  
• Pellikainen, J., Kataja, V., Ropponen, K., Kellokoski, J., Pietilainen, T., Bohm, J., Eskelinen, M., Kosma, V.-M. (2002). Reduced Nuclear Expression of Transcription Factor AP-2 Associates with Aggressive Breast Cancer. Clin. Cancer Res. 8: 3487-3495 [Abstract] [Full Text]