Telomerase activity in relation to p53 status and clinico-pathological parameters in breast cancer.
Cell cycle deregulation can occur at different levels in cancer. In human breast cancer it includes overexpression of cyclins D1 and E, down-regulation of cyclin-dependent kinase inhibitors and inactivation of the retinoblastoma and p53 tumor suppressor proteins. Telomerase activity is strongly associated with an immortal phenotype and expression of telomerase is linked to the cell cycle. We have recently demonstrated a connection between specific cell cycle defects within the pRB pathway and levels of telomerase activity in breast cancer. In the present study, 106 tumors were investigated for p53 gene and protein status. By single strand conformation polymorphism (SSCP) analysis, 15% showed mutations within exons 5-8 and by immunohistochemistry (IHC), 29% were p53 positive. Tumors with a telomerase activity above median (i.e., telomerase(high)) were significantly associated with p53 protein accumulation (p = 0.004), but not with p53 gene mutations. The strongest telomerase expression was found in tumors with p53 protein accumulation. Morphologic grade, estrogen and progesterone receptor expression differed significantly between the telomerase(high) and telomerase(low) groups (p < 0.0001, p = 0.016 and p = 0.046, respectively), but no difference was observed for stage or nodal status. Telomerase(high) tumors were significantly associated with a poor prognosis for node-negative (N0) patients (p = 0.008), but not for node-positive (N+) patients, whereas the opposite was demonstrated for tumors with p53 accumulation. The survival data indicated that telomerase expression has biological importance particularly for N0 tumors, suggesting that telomerase(low) tumors constitute a group of "pre-immortalized" tumors with a good prognosis.
Department of Pathology, Umeå University, Sweden. Goran.Roos@pathol.umu.se
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Roos
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Nilsson
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Cajander
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Nielsen
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Arnerlöv
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Landberg
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016158:Genes, p53; D006801:Humans; D008207:Lymphatic Metastasis; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D019098:Telomerase