 KLF4 expression pattern in relation to proliferation and differentiation markers in tongue carcinomas

PAPARELLA M. L; COZZARIN M. E.; COSO O. A; RAIMONDI A. R

Congreso; SAIC-SAE-SAFE; 2016

Oral squamous cell carcinoma (OSCC) is among the most prevalentcancers in the world and is characterized by high morbidityand few therapeutic options. Phenotypic alterations of carcinomacells progress OSCC to the more advanced stages, and the lackof differentiation is a main features of poorly differentiated OSCC.Krüppel-like factor 4 (KLF4) is highly expressed in differentiatedpostmitotic epithelial cells. Previously, we have reported expressionof Klf4 in murine tongue epithelium as well as epithelialdysplastic changes upon loss of Klf4. The aim of the study was toanalyze the expression of KLF4 in OSCC and the involvement inproliferation and differentiation of OSCC cells. We examined theexpression of KLF4, p53, Ki-67 and Keratin 14 (K14) in biopsiesof tongue SCC (SCC, n= 15) and normal human oral mucosa(NHOM, n=4) by immunohistochemistry. We evaluated percentageand intensity of staining. We found expression of KLF4 restrictedto intermediate and upper layers of the epithelium of the NHOM,however the supra-adjacent epithelium (SAE) to OSCC cells presenteda generalized expression throughout the epithelium. TheSCC presented a decrease in the labeling intensity compared withNHOM and SAE. The decrease was significant when comparedSCC and SAE (2.0+/-0.2, 2.9+/-0.1 p 50% of positivescells) and 100% of the SAE showed Ki-67 labeling in the basaland upper layer. K14 was expressed in the basal layer of theepithelium of the NHOM. We observed changes in the pattern ofK14 expression from localized (NHOM) to a generalized expressionthorough epithelium in SAE and SCC. Finally, only 20 % ofSCC showed p53 immunostaining. These results may reflect oralcarcinoma cells progression through the dedifferentiation processand warrant further studies. The changes in KLF-4 expressionbetween the SAE and SCC may represent different stages in oralcarcinogenesis.