Oestrogen receptors are prognostic factors in malignant peritoneal mesothelioma

Our plain-English summary of Oestrogen receptors are prognostic factors in malignant peritoneal mesothelioma, by K. Pillai, M.H. Pourgholami, T.C. Chua, et al (Journal of Cancer Research and Clinical Oncology, 2013).

The study

• Authors: K. Pillai, M.H. Pourgholami, T.C. Chua, D.L. Morris
• Journal: Journal of Cancer Research and Clinical Oncology
• Published: 2013;139(6):987-94
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer. Females are found to survive longer than males after treatment, suggesting a possible involvement of hormonal factors. Estradiol is involved in cellular proliferation of a number of cancers and acts mainly through oestrogen receptors (ERs). Hence, we examined the expression of oestrogen receptors with correlation to prognosis.

Methods: Oestrogen receptors expression was examined using immunohistochemistry on 42 paraffin-embedded sections of MPM tumours. Kaplan-Meier survival curves were analysed to determine the significance of ER expression in relation to prognosis.

Results: ER-β (nuclear) was detected in 33 (79 %) patients. ER-β was also detected in the cellular cytoplasm of 9 (21 %) patients. Presence of ER-β (nuclear) was associated with favourable survival (univariate analysis, P = 0.001), whereas the presence of ER-β (cytoplasm) was associated with a poor survival (P = 0.014). Multivariate Cox regression analysis revealed the absence of ER-β (nuclear) and the presence of ER-β (cytoplasm) to be independent predictive factors for poor disease outcome (hazard ratio 5.4, 95 % confidence interval 1.86-15.75; P = 0.002 and hazard ratio 8.0, 95 % confidence interval 1.8-34; P = 0.005), respectively. ER-α (nuclear) was detected in only 4 (9 %) of patients and not statistically significant (univariate analysis, P = 0.066).

Conclusion: The presence of ER-β (cytoplasm) is associated with poor prognosis. The favourable survival association observed in patients with ER-β (nuclear) raises a question about the molecular mechanisms of the tumorigenic roles of ER-β in each cellular compartment and requires further studies.

In plain English

The authors studied tumour tissue from 42 patients (20 men, 22 women) diagnosed with malignant peritoneal mesothelioma at St. George Hospital, Australia, from 1999 to May 2011. All had cytoreductive surgery and heated intraperitoneal chemotherapy. They stained it for oestrogen receptors alpha and beta and compared results with survival. Asbestos exposure was not examined. The authors classed 33 tumours as nuclear receptor beta (none stained in the cytoplasm) and 9 as cytoplasmic receptor beta (all also stained in the nucleus). Receptor alpha was found in only 4. The nuclear category was linked to better survival, the cytoplasmic to poorer. In multivariate analysis, hazard ratios for poor outcome were 5.4 (95% confidence interval 1.86 to 15.75) for tumours outside the nuclear category and 8.0 (1.8 to 34) for the cytoplasmic category. Women outlived men overall, and patients diagnosed under 60 did better. The authors concluded that these receptors and age at diagnosis may have prognostic significance. They could not judge receptor alpha in so few patients and did not consider comorbidities or lymph node spread. Several numbers in the article disagree.

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 single-hospital study of tumour specimens using immunohistochemistry, with Kaplan-Meier survival analysis and Cox proportional hazards (univariate and multivariate) analysis
• Who was studied: 42 patients (20 males, 22 females; median age 57, range 23 to 69) diagnosed with malignant peritoneal mesothelioma at St. George Hospital, Kogarah, NSW, Australia, 1999 to May 2011. All were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (cisplatin and doxorubicin). 35 had epithelial and 7 had sarcomatoid histology.
• Exposure: Not an asbestos exposure study. Patients' asbestos exposure was not assessed or reported. The factor studied was expression of oestrogen receptor alpha (nuclear) and oestrogen receptor beta (nuclear and cytoplasmic) in tumour tissue, measured by immunohistochemistry.
• Main results:
  • Of 42 patients' tumours, 33 (79%) were classed as nuclear oestrogen receptor beta and 9 (21%) as cytoplasmic receptor beta. The body text gives the nuclear figure as 78%. All 9 cytoplasmic-beta tumours also showed nuclear beta but were classified as cytoplasmic. The article states that none of the tumours classed as nuclear showed cytoplasmic beta.
  • In univariate analysis, the nuclear receptor beta category was associated with better overall survival (P = 0.001), and the cytoplasmic receptor beta category with poor overall survival (P = 0.014).
  • In multivariate Cox regression, two results were independent predictors of poor outcome. Being negative rather than positive for the nuclear receptor beta category gave a hazard ratio of 5.4 (95% CI 1.86 to 15.75; P = 0.002). Being in the cytoplasmic receptor beta category gave a hazard ratio of 8.0 (95% CI 1.8 to 34; P = 0.005). The tumours in the cytoplasmic category also stained in the nucleus.
  • Nuclear oestrogen receptor alpha was found in only 4 (9%) patients. Its association with survival was not statistically significant (univariate P = 0.066), and the authors said its significance could not be determined.
  • Within the nuclear-beta group, high staining scores (5 to 8) were linked to better prognosis than lower scores (0 to 4). Within the cytoplasmic-beta group, high scores were linked to poorer prognosis (P = 0.014).
  • Across all 42 patients, women had better survival than men in univariate analysis (P = 0.002). Gender was not significant in the multivariate analysis.
  • Patients diagnosed below age 60 had better survival. Age at diagnosis was also a significant independent factor in multivariate analysis.
• The authors' conclusion: The authors concluded that nuclear oestrogen receptor beta, cytoplasmic receptor beta and age at diagnosis may have prognostic significance and may be usable as markers to predict survival. They said the prognostic value of receptor alpha could not be determined, and that how the receptors work requires further study.
• Limitations the authors state:
  • Only 4 patients had oestrogen receptor alpha, too few to assess its prognostic value.
  • Other factors such as comorbidities and lymph node metastases were not considered and may have influenced the findings.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Prognosis, Immunohistochemistry, Hazard Ratio, confidence interval.

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