May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant pleural mesothelioma?

Our plain-English summary of May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant pleural mesothelioma?, by T.C. Mineo, V. Ambrogi, M.E. Cufari, et al (European Journal of Cardio-thoracic Surgery, 2010).

The study

• Authors: T.C. Mineo, V. Ambrogi, M.E. Cufari, E. Pompeo
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2010;38(3):245-52
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) proves useful in predicting prognosis and orientating therapy in many malignant tumours. Malignant pleural mesothelioma is an uncommon and lethal cancer for which there are limited treatment options. In this study, we evaluated the impact on prognosis and the influence on therapeutic strategy of immunohistochemical expression of COX-2, p21 and p27 in specimens from patients treated for malignant pleural mesothelioma.

Methods: We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 77 consecutive patients undergoing biopsy-plus-pleurodesis (n=6), pleurectomy-decortication (n=44) or extrapleural pneumonectomy (n=27) operations for malignant pleural mesothelioma between 1987 and 2007. Histology was of epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. Tumour node metastasis (TNM)-stage was I (n=21), II (n=36) and III (n=20). Therapies used were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=56) and neo-adjuvant chemotherapy plus adjuvant radiotherapy (n=4). From 2005 on, preoperative maximal standard uptake value (SUV(MAX)) was also measured by fluorodeoxyglucose positron-emission-tomography. Significance was investigated by Kaplan-Meier survival and Cox regression analysis.

Results: The median survival was 10 months. Survival was negatively influenced by histology (epithelioid vs biphasic vs sarcomatoid) (p=0.009), positive macroscopic resection margins (p=0.016), metastatic mediastinal lymph nodes (p=0.016), high COX-2 (p=0.0001) expression, low p21 (p=0.0001) expression and low p27 (p=0.001) expression. Conversely, neither the type of surgery (biopsy-plus-pleurodesis vs pleurectomy-decortication vs extrapleural pneumonectomy), nor preoperative SUV(MAX) (> or = 6.0 vs <6.0), or combined therapies (sole radiotherapy vs adjuvant radio-chemotherapy vs neo-adjuvant chemotherapy plus adjuvant radiotherapy) reached a significant level of difference. Cox regression analysis showed that only immunohistochemical triple combination of high COX-2 and low p21 and p27 expression influenced survival (p=0.0001, hazard ratio 4.7, 95% confidence intervals 3-11) regardless of type of treatment.

Conclusions: At Cox regression analysis, a combination of high COX-2 and low p21 and p27 expression resulted in the only negative prognosticator of malignant pleural mesothelioma. With this combination, less aggressive surgical options might be preferred.

Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

In plain English

This study, from a thoracic surgery unit at Tor Vergata University in Rome, looked back at tumour tissue from 77 patients (63 men, 14 women) who had surgery for malignant pleural mesothelioma between 1987 and 2007. The authors measured three proteins in the tissue, COX-2, p21 and p27, and compared the levels with how long patients survived. Median survival was 10 months. Looking at one factor at a time, survival was worse with tumour type (epithelioid vs biphasic vs sarcomatoid), with tumour visible to the naked eye at the edges of the removed tissue, with cancer in the lymph nodes in the centre of the chest, with high COX-2, with low p21 and with low p27. Type of operation, type of added therapy and reported asbestos exposure were not significantly linked to survival. When the factors were analysed together, no single factor remained significant. Only the combination of high COX-2 with low p21 and low p27 did, with a hazard ratio of 4.7 (95% confidence interval 3 to 11). No patient with this combination lived beyond 10 months. The authors concluded that these patients should preferably be considered only for minor operations. They noted the study was retrospective and relatively small.

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 review of surgical tumour specimens and clinical records (single-centre case series with survival analysis)
• Who was studied: 77 patients (63 men, 14 women, aged 27 to 82) operated on for malignant pleural mesothelioma between 1987 and 2007 at the Thoracic Surgery Division, Policlinico Tor Vergata University, Rome. Operations: biopsy-plus-pleurodesis (6), pleurectomy-decortication (44), extrapleural pneumonectomy (27). Histology: epithelioid (50), biphasic (17), sarcomatoid (10). 55 patients who had simple biopsy only were excluded for inadequate specimens and/or scant survival information.
• Exposure: The factors studied were tumour expression of COX-2, p21 and p27 (and p53), each scored as high or low. Asbestos exposure was recorded only as yes or no, as one clinical variable. No fiber types, products, jobs or doses were reported.
• Main results:
  • Median survival for the whole group was 10 months. Mean follow-up was 11.3 months (range 0.2 to 44 months).
  • In single-factor analysis, worse survival was associated with histology (p = 0.009), positive macroscopic resection margins (p = 0.016) and metastatic mediastinal lymph nodes (p = 0.016). In Table 1, median survival was 4 months for sarcomatoid, 9 for biphasic and 15 for epithelial tumours.
  • Type of surgery (p = 0.11), preoperative SUVmax on PET (p = 0.08) and type of combined therapy (p = 0.75) did not reach statistical significance.
  • Asbestos exposure was among the variables not significantly associated with survival. In Table 1, 59 exposed vs 28 unexposed patients had median survival of 8 vs 11 months, p = 0.08.
  • In single-factor analysis, high COX-2 (p = 0.0001), low p21 (p = 0.0001) and low p27 (p = 0.001) predicted worse survival. High p53 expression showed no significance.
  • Protein expression was not significantly related to the classic prognostic factors (stage, histology, surgery, therapy).
  • Only three (10%) patients with high COX-2 survived longer than 2 years, and all died a short time later. Among patients with the triple combination of high COX-2, low p21 and low p27, none survived more than 10 months.
  • In Cox regression, no single factor that was significant in single-factor analysis remained significant.
  • In Cox regression, only the triple combination of high COX-2, low p21 and low p27 significantly influenced survival: p = 0.0001, hazard ratio 4.7, 95% confidence interval 3 to 11.
  • Major complications occurred in 33% (9/27) of the extrapleural pneumonectomy group and less than 14% (6/44) of the pleurectomy-decortication group. There was one 30-day death, after extrapleural pneumonectomy.
• The authors' conclusion: The authors concluded that, on Cox regression, the combination of high COX-2 and low p21 and p27 expression was the only negative prognostic factor in malignant pleural mesothelioma. They wrote that for patients with this combination, therapeutic strategy should preferably consider only minor operations.
• Limitations the authors state:
  • The study was retrospective and its sample size was relatively limited.
  • The small number of biopsy-plus-pleurodesis patients and the non-consecutive way they were selected may bias interpretation of outcomes.
  • Treatments varied somewhat over the 20-year study period.
  • Disease-free interval could not be assessed because early recurrence could not be reliably detected in the early years. Survival was the only main end point.
  • The PET SUVmax analysis involved few patients (16).

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Biopsy, Pleurodesis, Pleurectomy/Decortication (P/D), Extrapleural Pneumonectomy (EPP), Histology, Epithelioid.

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