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

Abstract

Objectives: To evaluate the impact of immunohistochemical expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) in specimens from malignant pleural mesothelioma. Methods: We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 67 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 epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. TNM-stage was I (n=21), II (n=36) and III (n=20). Combined therapies were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=36) and neoadjuvant chemotherapy plus adjuvant radiotherapy (n=24). Results were investigated by Kaplan–Meier survival and Cox regression analysis. Results: Median survival was 13 months. Survival was negatively influenced by nonepithelial histology (P<0.01), positive resection margins (P<0.02), metastatic mediastinal lymph nodes (P<0.01), high COX-2 (P=0.001), low p21 (P<0.0001) and p27 (P=0.001) expression. Conversely, neither the type of surgery (biopsy vs. pleurectomy-decortication vs. extrapleural pneumonectomy), nor combined therapies (sole radiotherapy vs. adjuvant radio-chemotherapy vs. neoadjuvant 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, Odds Ratio 4.7, 95% confidence interval 3–11) regardless of kind of treatment. Conclusions: The presence of high expression COX-2 and low p21 and p27 expression significantly influences the prognosis of malignant pleural mesothelioma. Therapeutic strategy should consider these protein expressions, avoiding major operations in cases of combination of these factors