Sox2 Expression in Pulmonary Non-small Cell and Neuroendocrine Carcinomas

Abstract

Sox2 is a transcription factor that regulates embryonic stem cell pluripotency and drives commitment of airway precursor cells to basal-type and neuroendocrine cells in the developing lung. In cancer, Sox2 has been associated with a "stemness" phenotype that predicts for poor outcomes. We examined Sox2 expression in pulmonary neoplasms with respect to tumor type and differentiation, in comparison with conventional markers. Immunohistochemistry for Sox2, p63, CK5/6, and thyroid transcription factor-1 was performed on 121 tumors, including 34 adenocarcinomas (ACA), 32 squamous cell carcinomas (SCC), 14 typical carcinoids, 12 atypical carcinoids, 14 large cell neuroendocrine carcinomas, and 15 small cell carcinomas. Sox2 was strongly, diffusely expressed in 91% of SCC and 21% of ACA. Ninety-four percent of SCC coexpressed Sox2 and p63; 1 case was only focally positive for p63 but diffusely positive for Sox2. Twenty-nine percent of ACA were at least focally p63+; 12% were Sox2+/p63+. All of the ACA diffusely positive for Sox2 were p63 negative. Among non-small cell lung carcinoma overall, there was a significant association between Sox2+/p63- expression and high-grade histology (P = 0.02). Strong Sox2 expression was detected in 23% of low-grade and 72% of high-grade neuroendocrine carcinomas (P = 0.0004). Sox2 is highly expressed in concert with p63 in most SCC, but may also influence tumor differentiation in both non-small cell lung carcinomas and pulmonary neuroendocrine tumors.

SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

“…17 In lung cancer, SOX2 amplification and expression can be found in a large subset of squamous cell carcinomas. 9,10,17,18 Though at much lower frequencies, expression of SOX2 has also been reported to occur in adenocarcinomas of the lung. [17][18][19] In vitro studies suggest that SOX2 upregulation induces cell proliferation and anchorage-independent growth in squamous cell lung cancer cell lines.…”

“…9,10,17,18 Though at much lower frequencies, expression of SOX2 has also been reported to occur in adenocarcinomas of the lung. [17][18][19] In vitro studies suggest that SOX2 upregulation induces cell proliferation and anchorage-independent growth in squamous cell lung cancer cell lines. 9,10 Furthermore, SOX2 amplification and expression have been detected in preinvasive lesions of the lung, such as squamous dysplasia and carcinoma in situ.…”

Expression of MET and SOX2 genes in non-small cell lung carcinoma with EGFR mutation

“…Former studies suggest that overexpression of SOX2 may be an important way to activate the Nanog/Oct4/SOX2 pathway, which promotes tumor cell proliferation and is associated with short survival time of patients in stage I ADC (46). SOX2 is also activated in more advanced SCC tumors as others have reported (23,34). We conclude that SOX2 is activated not only by overexpression, but also through amplification as also mentioned by others (23,47).…”

“…The data indicate a discrepancy in the characteristics of SCC and ADC. Current comparative genomic hybridization studies have demonstrated that >90% of SCCs and ~20% of ADCs have copy number gain involving 3q26,4, essentially the same proportions that have been demonstrated to have high level SOX2 expression at the protein level (34). Of note, these studies have found high level amplification only in SCC (45).…”

“…High SOX2 expression was found in breast cancer (32), testicular germ cell tumors (33) and gastric adenocarcinoma (21). Expression of SOX2 protein has not been extensively studied in lung cancer; however, a recent study demonstrates that SOX2 is strongly and diffusely expressed in about 90% of pulmonary SCC and 20% of ADC (34). In the current study, all well-differentiated ADCs and 85.7% ADCs with an EGFR mutation expressing low levels of SOX2 suggest that SOX2 expression is associated with differentiation of ADC and inversely correlated with the activation of EGFR.…”