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Reduced p16 and Increased Cyclin D1 and pRb Expression Are Correlated With Progression in Cutaneous Melanocytic Tumors

Discipline of Pathology, The University of Sydney, Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia, Department of Anatomical Pathology, Royal Prince Alfred Hospital

Wei Li, PhD

Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia

Amira Sanki, MBBS

Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia

Marjorie H. Colman, BSc

Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia

Yee Hwa Yang, PhD

School of Mathematics and Statistics, The University of Sydney

John F. Thompson, MD

4Discipline of Surgery, The University of Sydney Sydney, New South Wales, Australia

Richard A. Scolyer, MD

Discipline of Pathology, The University of Sydney, Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia, richard.scolyer{at}email.cs.nsw.gov.au

The immunohistochemical expression of cell cycle proteins p16, cyclin D1, and pRb was assessed in 112 benign and malignant melanocytic tumors and correlated with tumor progression, prognosis, and outcome. Comparing benign and malignant tumors, there were significant differences in the median score for all 3 proteins, with decreased p16 (P = .000001), increased cyclin D1 (P = .01), and increased pRb in melanomas (P = .01). There was a progressive loss of expression of p16 with progression from benign naevi to primary melanomas and to metastases. p16 was significantly decreased in primary tumors from melanoma patients who developed recurrent disease (P = .0000013). Cyclin D1 and pRb showed a progressive increase in expression from benign to malignant tumors but with relative decreases in the more advanced tumors (thick primaries and metastatic melanomas). Alterations in cell cycle proteins involved in G1/S transition are implicated in melanocytic tumor progression and have a potential role in diagnosis and prognostication.

Key Words: melanoma • naevus • p16 • cyclin D1 • pRb • pathology

This version was published on October 1, 2009

International Journal of Surgical Pathology, Vol. 17, No. 5, 361-367 (2009)
DOI: 10.1177/1066896909336177


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