Zeitschrift für klinische und experimentelle Pathologie

Abstrakt

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

Giordano M, Macerola E, Boldrini L, Giannini R, Servadio A, Alì G, Melfi F, Lucchi M, Bertoglio P, Mussi A and Fontanini G

Background: The mutations detected in the promoter of the telomerase reverse transcriptase (TERT) gene,namely C228T and C250T, were first identified in melanoma and subsequently in several cancer models, notably glioma, thyroid cancer and bladder cancer. Recent findings demonstrate that mutation of the TERT promoter may be one of the most common genetic mechanisms contributing to telomerase activation in malignant cells. Mutation of the TERT promoter appears to be an indicator of worse outcome and is correlated with tumor aggressiveness and patient survival; however, to date the only two published studies reported a very low TERT mutation frequency in non-small cell lung cancer (NSCLC). Additionally, the relationship among the presence of these mutations, Tert expression and clinical outcome is unknown.

Materials and methods: In this study, the polymerase chain reaction and direct sequencing analysis of a TERT promoter region using formalin-fixed and paraffin-embedded tissues were performed to investigate the presence of TERT promoter mutations in a series of 95 early-stage (T1N0M0) NSCLC samples, including 48 adenocarcinomas (ADCs) and 47 squamous cell carcinomas (SCCs).Then, immunohistochemical (IHC) staining was performed to detect the expression of Tert.

Results and conclusions: We report that TERT promoter mutations are present in NSCLC with a frequency of 10.52%. TERT promoter mutations were identified in 7 (14.58%) ADCs and 3 (6.38%) SCCs. Tert was expressed in the cytoplasm of 55 samples out of 93 (59.1%) in 33 ADCs and 22 SCCs. The ADCs expressed Tert in a higher percentage of cases (71.7% vs. 46.8%). Although no correlations between the TERT mutations, Tert immunohistochemical expression, clinico-pathological parameters and survival were found in our series, this study represents a starting point for further research to better understand the molecular mechanisms involved in the transcriptional regulation of TERT and its role in lung cancer progression.