CKS1 expression in melanocytic nevi and melanoma

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// Anna A. Brożyna 1 , Andrew Aplin 2 , Cynthia Cohen 3 , Grant Carlson 3 , Andrew Joseph Page 4 , Michael Murphy 5 , Andrzej T. Slominski 6 and J. Andrew Carlson 7 1 Department of Tumor Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Oncology Centre - Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland 2 Department of Cancer Biology, BLSB 524, Thomas Jefferson University, Philadelphia, PA 19107, USA 3 Winship Cancer Institute, Emory University Hospital, Atlanta, GA 30322, USA 4 Pancreas, Liver, and Cancer Surgery, Piedmont Healthcare, Atlanta, GA 30309, USA 5 Department of Dermatology, UConn Health, Farmington, CT 06030, USA 6 Department of Dermatology, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL 35294, USA 7 Department of Pathology and Laboratory Medicine, Albany Medical College MC-81, Albany, NY 12208, USA Correspondence to: J. Andrew Carlson, email: carlsoa@mail.amc.edu Keywords: melanoma; Skp2; ubiquitination; p27; prognosis Received: November 07, 2017 Accepted: December 16, 2017 Published: December 23, 2017 ABSTRACT Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway.

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