Transcription Factor Pax6 Is Expressed In Human Soft Tissue Sarcomas And Confers Negative Impact On Patients' Survival

AIM: We investigated the expression of PAX6 in soft tissue sarcomas to evaluate its prognostic value. BACKGROUND: Transcription factor PAX6 has a decisive role in the development of the CNS, eye, pancreas and olfactory epithelium, and the pattern of PAX6 normal expression is restricted to those tissues. PAX6 is detected in various cancer cell lines, but very little is known about its expression in tumors, possible cancer-relevant functions and prognostic value. PAX6 is generally believed to be a tumor suppressor, based mainly on studies in glioblastoma. PAX6 has been detected in tumors of eye and pancreas, but the prognostic significance remains unclear. Soft tissue sarcomas (STS) are a relatively uncommon but deadly group of tumors with poor prognosis and few treatment options. Improving therapy efficacy requires discovery of novel biomarkers to identify high-risk patients who may benefit from adjuvant therapy, as well as to improve our understanding of the molecular pathology of STS. METHODS: Tissue microarrays from 249 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of PAX6 and TGF-beta. Western blotting was used to evaluate expression levels of PAX6 and TGF-beta in B3 lens epithelium cell line. RESULTS: PAX6 expression was detected in STS tissue samples. Both nuclear and cytoplasmic expression was observed, and there was a positive correlation between them (r=0.47; P CONCLUSIONS: We detected PAX6 in STS - the first tumor group with no developmental links to the normal sites of PAX6 expression. PAX6 appeared to confer a universal negative prognostic impact on DSS, irrespectively of clinical and pathological subgroups analyzed. PAX6 expression correlated with TGF-beta, and reciprocal upregulation may explain their synergistic negative effect on DSS. Citation Format: Yury Kiselev, Andrej Valkov, Ingvild Mikkola, Igor Snapkov, Sveinung Sorbye, Roy Bremnes, Lill-Tove Busund. Transcription factor PAX6 is expressed in human soft tissue sarcomas and confers negative impact on patients9 survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4722. doi:10.1158/1538-7445.AM2014-4722