Reduced p16 and increased cyclin D1 and pRb expression are correlated with progression in cutaneous melanocytic tumors.
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.
Karim
Rooshdiya Z
RZ
Discipline of Pathology, The University of Sydney, Sydney Melanoma Unit, Sydney Cancer Centre, Royal Prince Alfred Hospital and Melanoma Institute Australia.
Li
Wei
W
Sanki
Amira
A
Colman
Marjorie H
MH
Yang
Yee Hwa
YH
Thompson
John F
JF
Scolyer
Richard A
RA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009506:Nevus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1