Abstract 5031: Melanoma progression involves a profound nuclear to cytoplasmic shift of the transcription factor SUM-6 (specifically upregulated in melanoma gene six)

INTRODUCTION: SUM-6 is a human homeobox gene that encodes for a transcription factor, which plays a key role in normal embryogenesis. Overexpression of both the gene and nuclear protein has been shown to occur in a variety of cancers such as breast, colorectal, and pancreatic, and has been demonstrated to promote tumorigenesis. The purpose of the current study was to evaluate the expression of the SUM-6 protein, its clinical relevance, and biological function in melanoma. EXPERIMENTAL PROCEDURES: Immunohistochemistry using a specific SUM-6 antibody was performed on a tissue microarray consisting of 438 patient biopsies, which included benign and malignant melanocytic tumors. Double-blinded scoring of distinct nuclear and cytoplasmic SUM-6 staining was performed. SPSS 16.0 statistical package and Microsoft Excel were used to carry out the analyses of data. Analyses included the χ2 test and univariate analysis by the log-rank test in conjunction with the Kaplan-Meier survival curve for visualization. RESULTS: Nuclear staining of SUM-6 was detected in 100% of normal nevi (n = 19), 81% of dysplastic nevi (n = 32), 87% of melanoma in situ (n = 23), 79% of primary melanoma (n = 219), and 53% of metastatic melanoma (n = 145), whereas cytoplasmic staining was detected in 63%, 94%, 56%, 94%, and 97%, respectively. Univariate analysis revealed that five year disease-specific survival decreased significantly when SUM-6 was excluded from the nucleus and when SUM-6 levels were elevated in the cytoplasm (p = 0.001 and 0.019, respectively). CONCLUSIONS: We concluded that melanoma progression and metastasis is associated with a profound shift of transcription factor SUM-6 from the nucleus to the cytoplasm. It is interesting to note that in most other cancers, the SUM-6 protein was instead overexpressed in the nucleus. The patients in whom SUM-6 was excluded from the nucleus demonstrated a significantly worse prognosis than the patients who retained nuclear expression. These findings suggest that either the absence of nuclear expression or elevated cytoplasmic presence (or both) of SUM-6 may play a role in the progression of malignant melanoma. Citation Format: Laura J. Graziano, Xue Zhang, Yabin Cheng, Gang Wang, Mingwan Su, Magdalena Martinka, Youwen Zhou. Melanoma progression involves a profound nuclear to cytoplasmic shift of the transcription factor SUM-6 (specifically upregulated in melanoma gene six). [abstract]. In: Proceedings of the 107th Annual Meeting of the Am