Sex-determining region Y-box 2 amplification in preneoplastic squamous lesions of the lung

Summary Sex-determining region Y-box 2 gene at 3q26.33 has been identified as oncogene in squamous cell carcinoma occurring at different anatomical sites including the lung. Sex-determining region Y-box 2 protein expression and gene amplification have been found in preinvasive squamous cell lesions such as dysplasia and carcinoma in situ. We sought to evaluate sex-determining region Y-box 2 expression and amplification in a spectrum of premalignant squamous lesions ranging from squamous metaplasia to low- and high-grade dysplasia to in situ and invasive squamous cell carcinoma of the lung. Each lesion was taken from 1 of 3 study groups: 18 patients with concurrent squamous cell carcinoma, 17 patients with prior squamous cell carcinoma undergoing surveillance biopsies, and 11 patients with no history of squamous cell carcinoma. Sex-determining region Y-box 2 amplification occurred only in a subset of invasive squamous cell carcinoma (3/5; 60%) and their associated high-grade dysplasia (3/4; 75%), but not in any of the low-grade dysplasias (0/1; 0%) or metaplasias (0/9; 0%). No sex-determining region Y-box 2 amplification was observed in squamous preneoplastic lesions in surveillance biopsies without current evidence of squamous cell carcinoma or in benign lungs. Sex-determining region Y-box 2 protein expression was seen in all squamous lesions regardless of presence or degree of dysplasia. Our results suggest that sex-determining region Y-box 2 amplification is not an early event in squamous carcinogenesis and is important for progression in a subset of squamous cell carcinoma. It appears that sex-determining region Y-box 2 gene amplification in lung squamous carcinogenesis is not the only regulator of sex-determining region Y-box 2 protein expression.