Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma.
The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR) in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction-based assay (TRAP). High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastases = 54.5, lymph node metastases = 56.5). Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9). Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.
Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, Dallas 75235-9039, USA.
R D
RD
Ramirez
S
S
D'Atri
E
E
Pagani
T
T
Faraggiana
P M
PM
Lacal
R S
RS
Taylor
J W
JW
Shay
D006801:Humans; D017403:In Situ Hybridization; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D008938:Mitosis; D009361:Neoplasm Invasiveness; D009508:Nevus, Pigmented / Q000201:enzymology* / Q000473:pathology; D012313:RNA / Q000032:analysis; D012878:Skin Neoplasms / Q000201:enzymology*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics
D012313:RNA; D019098:Telomerase