Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma

Our plain-English summary of Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma, by G. Zhang, D.L. Yang, G. Zheng, et al (Oncology Letters, 2020).

The study

• Authors: G. Zhang, D.L. Yang, G. Zheng, Y. Liang
• Journal: Oncology Letters
• Published: 2020;19(6):3871-3880
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant peritoneal mesothelioma (MPeM) is an incurable cancer strongly associated with asbestos exposure and characterised by poor prognosis. The aim of the present study was to elucidate the prognostic and predictive value of CD146 and survivin expression in MPeM. Diagnostic biopsies from 60 patients with MPeM were collected and analysed for CD146, survivin and Ki-67 expression using immunohistochemistry. Complete clinical and follow-up information was obtained from patients' records. CD146 was expressed in 31/60 MPeM specimens and survivin in 34/60 specimens, with both expression levels being significantly associated with the Ki-67 labelling index (Ki-67LI). Kaplan-Meier and univariate Cox regression analyses revealed that a lower peritoneal cancer index (PCI), tumour-directed treatment, stage I, lower Ki-67LI and lower CD146 and survivin expression had a statistically positive effect on overall survival (OS). Cox regression analysis revealed that PCI [hazard ratio (HR)=1.99; 95% CI, 1.04-3.83; P=0.038], survivin (HR=1.47; 95% CI, 1.03-2.10; P=0.034) and treatment protocol including intraperitoneal chemotherapy (HR=0.28; 95% CI, 0.14-0.57; P=0.013) and systemic chemotherapy (HR=0.13; 95% CI, 0.04-0.42; P=0.013) retained independent prognostic significance for OS. All of these were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted and observed survival. The C-index of the nomogram for predicting OS was 0.77. A lower PCI, intraperitoneal chemotherapy, systemic chemotherapy and a lower level of survivin were powerful prognostic markers in patients with MPeM. The proposed nomogram provides individual survival prediction for patients with MPeM.

Copyright: © Zhang et al.

In plain English

This hospital study looked at 60 patients diagnosed with malignant peritoneal mesothelioma, a cancer of the abdominal lining, at Cangzhou Central Hospital, China, between August 2015 and September 2018. Asbestos exposure was documented for 86.7% of them. The authors suggested that this high rate, and the many women among the patients, could be attributed to hand-spinning of asbestos yarn in the 1970s. The authors stained diagnostic biopsies for three proteins (survivin, CD146 and Ki-67) and compared the results with survival. Survivin was found in 34 of 60 tumour samples and CD146 in 31 of 60. None of the three proteins was found in normal or inflamed peritoneal tissue. Median survival was 9.25 months. In the multivariate analysis, survivin (hazard ratio 1.47, 95% CI 1.03 to 2.10), the peritoneal cancer index (a score of tumour spread in the abdomen) and chemotherapy, compared with supportive care, remained linked to survival. Asbestos exposure was not significantly associated with survival. A prediction chart built from the peritoneal cancer index, TNM stage, survivin and treatment had a C-index of 0.77, although stage was not significant in the multivariate analysis. The authors called for larger studies and prospective validation.

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: Prognostic study of patients' diagnostic biopsies, tested for survivin, CD146 and Ki-67 with immunohistochemical staining, combined with clinical and follow-up data from medical records; survival analysis and construction of a prediction nomogram
• Who was studied: 60 patients newly diagnosed with malignant peritoneal mesothelioma (MPeM) at Cangzhou Central Hospital, China, August 2015 to September 2018: 22 men and 38 women, median age 62 (range 42 to 84). 38 received chemotherapy and 22 best supportive care. Controls were 60 peritonitis tissue samples and 60 normal peritoneal tissue samples.
• Exposure: Asbestos exposure was taken from medical records. No fiber type, product or dose is given. The authors suggested that the exposures could be attributed to hand-spinning of asbestos yarn in the 1970s. The main factors studied were tumour levels of survivin, CD146 and Ki-67, plus the peritoneal cancer index (PCI), TNM stage and treatment.
• Main results:
  • Asbestos exposure was documented for 86.7% of the 60 patients (52 of 60 in Table I).
  • In the univariate analysis, asbestos exposure (yes vs. no) was not significantly associated with overall survival: hazard ratio 0.96, 95% CI 0.43 to 2.14, P=0.900.
  • Survivin (5% or more of cells stained) was found in 34 of 60 tumour specimens (56.67%), and CD146 in 31 of 60 (51.67%).
  • Survivin and CD146 levels were both correlated with the Ki-67 labelling index, a marker of dividing cells (survivin r=0.425, P=0.001; CD146 r=0.362, P=0.004).
  • Survivin, CD146 and Ki-67 were negative in normal mesothelium and in peritonitis specimens.
  • Median overall survival for the 60 patients was 9.25 months (range 1 to 48 months). Five patients were still alive at the final analysis.
  • In the multivariate Cox analysis, survivin (positive vs. negative) kept independent prognostic significance: hazard ratio 1.47, 95% CI 1.03 to 2.10, P=0.034.
  • In the multivariate analysis, PCI (30 or less vs. over 30) had a hazard ratio of 1.99 (95% CI 1.04 to 3.83). The text gives P=0.038; Table III gives 0.044. The authors state that a high PCI indicated poor prognosis.
  • Compared with best supportive care, intraperitoneal chemotherapy (hazard ratio 0.28, 95% CI 0.14 to 0.57, P less than 0.001) and systemic chemotherapy (hazard ratio 0.13, 95% CI 0.04 to 0.42, P less than 0.001) kept independent prognostic significance in the multivariate analysis.
  • CD146 was linked to prognosis in the univariate analysis, but this was not confirmed in the multivariate analysis. The same was true for Ki-67 and stage. In the multivariate analysis, TNM stage had a hazard ratio of 1.56, 95% CI 0.89 to 2.76, P=0.123.
  • In the univariate analysis, age, sex and histological type were not associated with prognosis.
  • A nomogram using PCI, TNM stage, survivin and treatment protocol had a C-index of 0.77 for predicting overall survival. TNM stage was included even though it was not significant in the multivariate analysis.
• The authors' conclusion: The authors concluded that PCI, tumour-directed treatment (intraperitoneal and systemic chemotherapy) and survivin levels appear to serve vital roles in influencing survival time. They proposed their nomogram as a tool to predict outcomes in MPeM.
• Limitations the authors state:
  • The authors said the sample size could be increased to confirm the associations of age and histological type with prognosis.
  • All patients received conservative (non-surgical) treatment. PCI and TNM grades were based on CT imaging and may differ from surgical grading.
  • The authors said the nomogram should be validated with additional data and prospectively.

Topics

Medical terms in this study, explained in our Lexicon: Overall Survival, Peritoneal Mesothelioma, Asbestos Exposure, Prognosis, Ki-67, Immunohistochemistry, Peritoneal Cancer Index (PCI), Hazard Ratio.

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• Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series — J.C. Leinwand, R.N. Taub, et al. (2020)
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