Overexpression and ratio disruption of ΔNp63 and TAp63 isoform equilibrium in endometrial adenocarcinoma: correlation with obesity, menopause, and grade I/II tumors

• Published in: Journal of cancer research and clinical oncology Vol. 138; no. 8; pp. 1271 - 1278
• Main Authors: Vakonaki, Eleni, Soulitzis, Nikolaos, Sifakis, Stavros, Papadogianni, Danae, Koutroulakis, Dimitrios, Spandidos, Demetrios A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2012
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Cancer Research; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Menopause; Middle Aged; Neoplasm Grading; Obesity - pathology; Oncology; Original Paper; Protein Isoforms - genetics; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription Factors - genetics; Tumor Suppressor Proteins - genetics; Up-Regulation - genetics; Biomarkers; mRNA; Real-time PCR; p63; Endometrium
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-012-1200-8

Purpose p63 plays an important role in several intracellular processes such as transcription activation and apoptosis. p63 has two N-terminal isoforms, TAp63 and ΔNp63. TAp63 isoform has p53-like functions, while ΔNp63 acts as a dominant negative inhibitor of the p53 family and is considered oncogenic. Although p63 and its isoforms are overexpressed in a wide variety of human malignancies such as cervical, head and neck, and lung cancer, their role in endometrial carcinoma has not been investigated. Methods We measured by quantitative real-time polymerase chain reaction the mRNA expression of TAp63 and ΔNp63 in a series of 20 endometrioid adenocarcinomas paired with adjacent normal tissue. Results TAp63 isoform exhibited 1.8-fold overexpression in malignant samples, while ΔNp63 was 4.3-fold overexpressed in cancer specimens. Further analysis revealed that the ΔN/TA isoform ratio shifted from 0.5 in normal samples to 1.2 in tumor specimens. Statistical analysis also revealed an association of TAp63 expression with high body mass index ( p  = 0.034), late menopause ( p  = 0.020), and lower tumor grade ( p  = 0.034). ΔNp63 was also correlated with grade I/II tumors ( p  = 0.044). Conclusions These results indicate that both p63 isoforms and especially ΔNp63 play an important role in the development and progression of grade I/II endometrial adenocarcinoma, especially in obese and late-menopause women.