Loss of heterozygosity and immunoexpression of PTEN in oral epithelial dysplasia and squamous cell carcinoma

Abstract

Introduction: Oral epithelial dysplasia (OED) is a risk factor for developing subsequent oral squamous cell carcinoma (OSCC). Loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OED. It is still unclear if Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) allelic loss also occurs in initial stage malignant lesions and if the allelic loss is involved as one of the mechanisms of oral carcinogenesis. Thus, this study objective investigate LOH of PTEN gene and the immunohistochemical expression of the protein in OED and OSCC samples.

Material and methods: Formalin-fixed paraffin-embedded samples of 19 OEDs and 16 OSCCs were included to immunohistochemistry and LOH analysis. Two polymorphic microsatellite markers (AFMA086WG9 and D10S1765) located in chromosome 10 were used in this study for LOH analysis. For immunohistochemical analysis, 5 random fields with 400× magnification were evaluated quantitatively and qualitatively in epithelial and neoplastic cells.

Results: AFMA086WG9 marker only demonstrated LOH in OEDs cases (10.5%). D10S1765 marker demonstrated LOH in 57.2% of OEDs and 50% of OSCCs. Higher nuclear immunostaining was detected in cases of OSCCs when compared to OEDs (p < .001) and there was strong cytoplasmic immunoexpression in OSCCs (p < .045).

Conclusions: We provide evidence that the allelic loss of PTEN is present in premalignant oral lesions and OSCCs, however the LOH of PTEN does not seems to influence its protein expression.

Keywords: Immunohistochemistry; Loss of heterozygosity; Oral epithelial dysplasia; Oral squamous cell carcinoma; PTEN.