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

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

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigaciones Clínicas

Oral squamous cell carcinoma (OSCC) isamong the most prevalent cancers in the world and is characterized by highmorbidity and few therapeutic options. Phenotypic alterations of carcinomacells progress OSCC to the more advanced stages, and the lack ofdifferentiation is a main features of poorly differentiated OSCC. Krûppel-likefactor 4 (KLF4) is highly expressed in differentiated postmitotic epithelialcells. Previously, we havereported expression of Klf4 in murine tongue epithelium as well as epithelial dysplasticchanges upon loss of Klf4. The aim of the study was to analyze the expression of KLF4 inOSCC and the involvement in proliferation and differentiation of OSCC cells. Weexamined the expression of KLF4, p53, Ki-67 and Keratin 14 (K14) in biopsies oftongue SCC (SCC, n= 15) and normal human oral mucosa (NHOM, n=4) byimmunohistochemistry. We evaluated percentage and intensity of staining. Wefound expression of KLF4 restricted to intermediate and upper layers of theepithelium of the NHOM, however the supra-adjacent epithelium (SAE) to OSCCcells presented a generalized expression throughout the epithelium. The SCCpresented a decrease in the labeling intensity compared with NHOM and SAE. The decreasewas significant when compared SCC and SAE (2.0+/-0.2, 2.9+/-0.1 p 50% of positives cells) and 100% of the SAEshowed Ki-67 labeling in the basal and upper layer. K14 was expressed in thebasal layer of the epithelium of the NHOM. We observed changes in the patternof K14 expression from localized (NHOM) to a generalized expression thoroughepithelium in SAE and SCC. Finally, only 20 % of SCC showed p53 immunostaining.These results mayreflect oral carcinoma cells progression through the dedifferentiation processand warrant further studies. The changes in KLF-4expression between the SAE and SCC may representdifferent stages in oral carcinogenesis.