CKS1 expression in melanocytic nevi and melanoma

• Type of Material: Article
• Authors: Anna A. Brozyna, Nicolaus Copernicus University; Andrew Aplin, Thomas Jefferson University; Cynthia Cohen, Emory University; Grant Carlson, Emory University; Andrew Joseph Page, Piedmont Healthcare; Michael Murphy, University of Connecticut Health Center; Andrzej T. Slominski, University of Alabama Birmingham; J. Andrew Carlson, Albany Medical College
• Language: English
• Date: 2018-01-09
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © Brozyna et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.23648
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 9
• Issue: 3
• Start Page: 4173
• End Page: 4187
• Grant/Funding Information: This study was supported by grants from NIH (R01 CA125103) and (R21AR066505, 1R01AR056666 and 1 R01AR071189 to ATS), by the clinical revenues and generous donors to the Divisions of Dermatology and Dermatopathology, Department of Pathology, Albany Medical College and grant 2014/15/B/NZ4/00751 from National Science Centre, Poland to AAB.
• Keywords: INHIBITOR P27(KIP1); Oncology; Skp2; MALIGNANT-MELANOMA; CYCLIN D1; UBIQUITIN LIGASE; prognosis; P27(KIP1) EXPRESSION; B-RAF; CANCER CELLS; Science & Technology; tumor progression; Cell Biology; Life Sciences & Biomedicine; CUTANEOUS MELANOMA; melanoma; p27; ubiquination; S-PHASE; COLORECTAL-CARCINOMA
• Research Categories: Health Sciences, Oncology

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.