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Low level expression of human telomerase reverse transcriptase predicts cancer-related death and progression in embryonal carcinoma

  • Original Article – Cancer Research
  • Published:
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Abstract

Introduction

hTERT (human telomerase reverse transcriptase) is a catalytic subunit of the enzyme telomerase and has a role in cell proliferation, cellular senescence, and human aging.

Materials and methods

The purpose of this study was to evaluate the expression and significance of hTERT protein expression as a prognostic marker in different histological subtypes of testicular germ cell tumors (TGCTs), including 46 embryonal carcinomas, 46 yolk sac tumors, 38 teratomas, 84 seminomas as well as two main subtypes of seminomas and non-seminomas using tissue microarray (TMA) technique.

Results

The results showed that there is a statistically significance difference between the expression of hTERT and various histological subtypes of TGCTs (P < 0.001). In embryonal carcinoma, low level expression of hTERT protein was significantly associated with advanced pT stage (P = 0.023) as well as tunica vaginalis invasion (P = 0.043). Moreover, low level expression of hTERT protein was found to be a significant predictor of worse DSS (log rank: P = 0.011) and PFS (log rank: P = 0.011) in the univariate analysis. Additionally, significant differences were observed (P =0.021, P =0.018) with 5-year survival rates for DSS and PFS of 66% and 70% for moderate as compared to 97% and 97% for high hTERT protein expression, respectively.

Conclusion

We showed that hTERT protein expression was associated with more aggressive tumor behavior in embryonal carcinoma patients. Also, hTERT may be a novel worse prognostic indicator of DSS or PFS, if the patients are followed up for more time periods.

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Data availability

The analyzed data during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the grant from Iran University of Medical Sciences (number: 1397-2-28-12348).

Author information

Author notes

  1. Marzieh Shahin and Leili Saeednejad Zanjani contributed equally to this work and are joint first authors.

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Marzieh Shahin, Maryam Abolhasani, Mahtab Rahbar, Mojgan Asgari & Zahra Madjd

  2. Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Leili Saeednejad Zanjani, Maryam Abolhasani, Mojgan Asgari & Zahra Madjd

  3. Hasheminejad Kidney Center, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Maryam Abolhasani & Mojgan Asgari

  4. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Zahra Madjd

Authors
  1. Marzieh Shahin
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  2. Leili Saeednejad Zanjani
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Contributions

ZM designed and supervised the work; MS gathered the paraffin-embedded tissues, collected the patient data, examined hematoxylin and eosin slides, and marked the most representative areas in different parts of the tumor for preparing the TMA blocks; LS performed the immunohistochemistry examinations, prepared the information of patient survival outcomes, analyzed and interpreted the data as well as wrote the manuscript; MAa, and MAb scored TMA slides after immunohistochemical staining; MR was a consultant on this project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zahra Madjd.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Human Research Ethics Committee of Iran University of Medical Sciences in Iran (Ref no: IR.IUMS.REC1397.443). All the procedures were performed in accordance with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants, parents or legally authorized representatives of participants under legal age years old at the time of sample collection with routine consent forms.

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Supplementary Fig.

 1: Isotype controls in immunohistochemistry staining for confirming nonspecific binding of primary antibody. In embryonal carcinomas (A), yolk sac tumors (B), teratomas (C), seminomas (D), adjacent normal tissue (E), and in benign tumor tissue (F)

Supplementary Fig.

 2: Kaplan–Meier curves for disease-specific survival (DSS) and progression-free survival (PFS) based on hTERT protein expression level in non-seminomatous GCT. Kaplan–Meier survival curves showed that low levels of hTERT expression are not significantly related to (A) DSS and (B) PFS (P = 0.161, P = 0.148), respectively in non-seminomatous GCT samples

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Shahin, M., Saeednejad Zanjani, L., Abolhasani, M. et al. Low level expression of human telomerase reverse transcriptase predicts cancer-related death and progression in embryonal carcinoma. J Cancer Res Clin Oncol 146, 2753–2775 (2020). https://doi.org/10.1007/s00432-020-03319-2

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  • DOI: https://doi.org/10.1007/s00432-020-03319-2

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