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Pathology. 2018 Nov 19. pii: S0031-3025(18)30289-7. doi: 10.1016/j.pathol.2018.08.019. [Epub ahead of print]

Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma.

Author information

1
Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
2
Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Molecular Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: zahra.madjd@yahoo.com.
3
Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran; Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran.
4
Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Basic Sciences/Medical Surgical Nursing, Tehran University of Medical Sciences, Tehran, Iran.
5
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States.
6
Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods.

KEYWORDS:

clear cell renal cell carcinoma (ccRCC); hTERT; protein expression; renal cell carcinoma (RCC); tissue microarray (TMA)

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