Differential expression of retinoic acid receptors in normal and malignant esophageal tissues
Anupam Kumar, Jatinder Kaur, Tushar Kant Chattopadhyay, Meera Mathur and Ranju Ralhan
The chemopreventive and chemotherapeutic activities of retinoids may be attributed to their ability to modulate growth, differentiation and apoptosis of epithelial cells, suppress or reverse epithelial carcinogenesis. Many of these effects of retinoids result from modulation of genes by two distinct classes of retinoid receptors: RARs and RXRs, alterations in their expression may lead to tumorigenesis. To determine whether alterations in expression of retinoid receptors are related to the development of esophageal squamous cell carcinomas (ESCCs), the expression of RARa, b, g and RXRa was studied in 50 untreated primary esophageal carcinomas and 19 distant normal tissues by immunohistochemistry. RARb expression was observed in 18/50 (36%) ESCCs, while 16/19 (84%) of matched histologically normal esophageal tissues displayed RARb immunopositivity (p=0.001, OR=3.405). Significant increase in RARa immunopositivity was observed in ESCCs (40/50; 80%) as compared to normal tissues (9/19 cases; 47%) (p=0.008; OR=2.77). RARg expression was observed in ESCCs (37/50cases; 74%) as compared to normal tissues (16/19; 84%); without significant difference. However, poorly differentiated esophageal cancer showed marked decrease in RARg immunopositivity (p=0.017; OR=6.0). Interestingly, increased expression of RXRa was observed in 43/50 (86%) ESCCs in comparison with (10/19; 53%) normal tissues (p=0.003; OR=3.09). Logistic regression analysis revealed RARg-/RXRa+ phenotype as most significantly associated with dedifferentiation of the tumor (p=0.014; OR=11.0). The hallmark of the study was the significant increase in expression of RARa and RXRa proteins and loss of expression of RARb protein in ESCCs in comparison with the distant normal epithelia.