Detection of telomerase activity and correlation with mitotic and apoptotic indices, Ki-67 and expression of cyclins D1 and A in cutaneous melanoma.
Telomerase plays a key role in carcinogenesis. It is activated in most immortal cell lines and human cancers, including cutaneous melanoma (CM). Increased cell proliferation and deregulation of the cell cycle occur in human cancers. Links between telomerase activity (TA), cell proliferation, cell death and expression of cell-cycle regulators have not been extensively elucidated in CM. In this study, we investigated TA, mitotic index (MI), apoptotic index (AI), Ki-67 and nuclear positivity of cyclins D1 and A (Ki-67+ N/1,000, cyclin D1+N/1,000, cyclin A+N/1,000) in 42 primary cutaneous melanomas (PCMs). TA was detected in all cases and directly correlated with MI, Ki-67+N/1,000, cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001); it was not correlated with AI. When subdividing PCMs into radial and vertical growth phase melanomas (RGPMs, VGPMs), a correlation was maintained only with MI (p < 0.005) and cyclin D1 +N/1,000 (p < 0.005). Although MI and Ki-67+N/1,000 were highly correlated with cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001) when considering all cases together, a high correlation was found in the RGPM and VGPM groups between cyclin A+N/1,000 and Ki-67+N/1,000 only (p < 0.001), thus suggesting that cyclin A is more closely correlated with cell proliferation than cyclin D1. Our results further support the association between TA, tumor cell proliferation and cyclin D1 and A expression in PCM, though it is possible that links between TA and proliferation, on the one hand, and TA and cyclin D1 expression, on the other, might occur following various pathways.
Miracco
C
C
Institute of Pathological Anatomy and Histology, University of Siena, Italy.
Pacenti
L
L
Santopietro
R
R
Biagioli
M
M
Fimiani
M
M
Perotti
R
R
Rubegni
P
P
Pirtoli
L
L
Luzi
P
P
D017209:Apoptosis; D019925:Cyclin A / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008938:Mitosis; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*
D019925:Cyclin A; D019394:Ki-67 Antigen; D019938:Cyclin D1; D019098:Telomerase