Expression of inflammatory molecules cyclooxygenase-2 and forkhead box protein 3 in Wilms’ tumor microenvironment and their clinicopathological significance

Abstract

Background and purpose The role of inflammation in cancer has been reported in various adult malignant neoplasms. Cyclooxygenase-2 (COX-2) is overexpressed in invasive breast carcinoma, colonic adenocarcinomas, as well as other tumors, and inhibitors of COX-2 have increasingly become therapeutic alternatives in many tumors. Forkhead box protein 3 (FOXP-3) transcription factor is important for the development of Tregs and hence maintenance of immunologic self-tolerance. Activity of Tregs is increased in lung cancer, gastric, and several adult-onset tumors, and they play a role in suppressing the antitumor immune responses. However, the exact role of these inflammatory molecules in pediatric malignancies especially Wilms’ tumor (WT) has not yet been fully addressed. Aim The aim of the present study was to investigate the expression of the inflammatory molecules COX-2 and FOXP-3 in WTs and their possible association with the different clinicopathological parameters. Patients and methods In this study, 21 formalin-fixed paraffin-embedded specimens of WTs were evaluated. Anaplasia [unfavorable histology (UFH)] was found in 31.6% of the studied tumors. Protein expression of COX-2 and FOXP-3 was investigated using immunohistochemistry. The degree of expression of both COX-2 and FOXP-3 expression was semiquantitatively assessed for each of the studied tumors using modified H-scoring. Results The present study revealed that COX-2 was expressed in the cytoplasm of all studied cases (100%). Its expression was higher in anaplastic WT (UFH) (median H-score, 200) compared with tumors with favorable histology (median H-score, 160). However, this difference was not statistically significant (P=0.167). On the contrary, FOXP-3 expression in WT was mostly low. Its expression varied between an H-score of 10 and 130 (median, 20). No significant difference in expression was noted between favorable histology versus UFH tumors. The present study also demonstrated a significant positive association between expression of COX-2 and FOX-P3 in WTs (P=0.033). Conclusion Our results show that COX-2 is strongly expressed in all WTs with a trend toward higher expression in UFH ones. Furthermore, the significant association between COX-2 expression and FOXP-3 expression in the studied cases suggests that inhibition of COX-2 may lead to an associated suppression of FOXP-3 activity and thereby enhancing the antitumor immune responses in these patient, which is an interesting finding that needs to be further explored.