Is survivin expression prognostic or predictive in malignant pleural mesothelioma?

Our plain-English summary of Is survivin expression prognostic or predictive in malignant pleural mesothelioma?, by J. Hmeljak, N. Erčulj, V. Dolžan, et al (Virchows Archiv, 2013).

The study

• Authors: J. Hmeljak, N. Erčulj, V. Dolžan, J. Pižem, I. Kern, V. Kovač, M. Cemažar, A. Cör
• Journal: Virchows Archiv
• Published: 2013;462(3):315-21
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is an incurable cancer strongly associated with asbestos exposure and characterised by poor response to treatment. The inhibitor-of-apoptosis protein family member survivin is involved in apoptosis and proliferation and is expressed in cancer cells only. The aims of the present study were to elucidate whether survivin expression is associated with tumour cell apoptosis and proliferation and to assess the prognostic and predictive value of survivin expression in malignant pleural mesothelioma. Archival pleural mesothelioma tissue samples from 101 patients were immunohistochemically analysed for nuclear expression of survivin, for proliferation with the use of Ki-67 as marker and for apoptosis using active caspase-3 as a marker. Staining results and clinical data were included in a survival analysis. Survivin was highly expressed in tumour cell nuclei in all samples and this correlated positively with both apoptosis and proliferation, but did not have a significant prognostic value. We found significantly higher survivin expression in patients who responded to chemotherapy compared to patients with progressive disease. Survivin expression might contribute to treatment response prediction, but survivin expression in malignant pleural mesothelioma did not have prognostic significance.

In plain English

The authors examined stored tumour tissue from 101 patients diagnosed with malignant pleural mesothelioma between 1996 and 2006 at a clinic in Golnik, Slovenia. They stained the samples for survivin, a protein that blocks cell death, and for markers of cell division (Ki-67) and cell death (active caspase-3). They then compared these results with survival and treatment response. Survivin was found in tumour cell nuclei in every sample, with a median of 67% of nuclei positive. Higher survivin went along with more cell death and more cell division. Survivin was not linked to survival (hazard ratio 0.99, 95% CI 0.99–1.01; P=0.30). Patients given tumour-directed treatment had higher survivin than patients given only supportive care or no treatment (P=0.01). Among 49 patients treated with chemotherapy, those who responded had slightly higher survivin than those whose disease was stable or progressing (P=0.03). Occupational and environmental asbestos exposure were not significantly linked to survival. The authors concluded that survivin may help predict treatment response and called for prospective studies. They noted the small sample and that results were not corrected for multiple testing.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of archival tumour biopsy tissue (immunohistochemistry) linked to clinical records, with Cox survival analysis
• Who was studied: 101 patients with malignant pleural mesothelioma (65 males, 36 females) diagnosed 1996 to 2006 at the University Clinic of Pulmonary and Allergic Diseases, Golnik, Slovenia
• Exposure: The main factor studied was nuclear survivin expression in tumour tissue, together with Ki-67 (cell division) and active caspase-3 (cell death). Asbestos exposure (occupational, environmental), recorded by clinical interview, was included as one factor in the survival analysis. No fiber types are given.
• Main results:
  • Nuclear survivin was present in all tumour samples, with a median of 67% of tumour cell nuclei positive
  • Survivin was positively correlated with the cell-death index (Spearman's rho 0.52, P less than 0.001) and with the cell-division index (rho 0.28, P=0.005)
  • Survivin expression was not associated with overall survival: HR 0.99 (95% CI 0.99–1.01), P=0.30. Above-median survivin gave HR 0.71 (0.48–1.07), P=0.10.
  • Median survivin expression was 67.7 in patients given tumour-directed treatment versus 55.5 in patients given best supportive care or no treatment (P=0.01)
  • In 49 chemotherapy-treated patients with response data, median survivin was 68.6 in those with partial or complete response versus 66.6 in those with stable or progressing disease (P=0.03)
  • Median overall survival was 11 months (range 0–108) for the whole cohort, 24 months for patients given oncological treatment, and 9 months for those given best supportive care only or no treatment
  • In the multivariate analysis, only epithelioid histological type (HR 0.30, 95% CI 0.15–0.63) and oncological treatment (HR 0.30, 95% CI 0.17–0.54) remained independently linked to longer survival
  • Asbestos exposure was not significantly associated with survival: occupational HR 0.90 (95% CI 0.37–2.20, P=0.82), environmental HR 0.96 (0.41–2.26, P=0.92). The reference group is not stated.
• The authors' conclusion: The authors concluded that nuclear survivin was not an independent indicator of overall survival, but was higher in patients who responded to tumour-directed treatment. They said this warrants prospective studies of survivin as a predictive marker.
• Limitations the authors state:
  • The study was exploratory with a small sample size, and no corrections for multiple testing were made
  • Because many treatment protocols were used, patients were only coarsely grouped as tumour-directed treatment versus best supportive care
  • Cytoplasmic survivin was not measured
  • The idea that survivin predicts treatment response is a hypothesis that needs a prospective study in a large cohort

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Apoptosis, Ki-67, Chemotherapy.

Related studies

• BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients — J. Hmeljak, N. Erčulj, et al. (2011)
• Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma — M. Meerang, K. Bérard, et al. (2016)
• Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma — K. Goričar, V. Kovač, et al. (2015)
• Survivin is a negative prognostic factor in malignant pleural effusion — E. Arellano-Orden, B. Romero-Romero, et al. (2018)
• Preclinical development of HIvax: Human survivin highly immunogenic vaccines — P.R. Hoffmann, M. Panigada, et al. (2015)
• Fowlpox-based survivin vaccination for malignant mesothelioma therapy — P. Bertino, M. Panigada, et al. (2013)

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