Immunohistochemical expression of receptors for luteinizing hormone-releasing hormone (LHRHR) in muscle-invasive Urothelial carcinoma of urinary bladder: a potential predictive marker for targeted cytotoxic LHRH hybrid analogs

Abstract

Abstract Background Recurrent disease following failed chemotherapy for muscle-invasive urothelial carcinoma (UC) has no universally accepted treatment guidelines. Receptors for luteinizing hormone-releasing hormone (LHRHR) have recently been identified in urothelial cancer cell lines as well as tissue samples. These receptors can be used as target for cytotoxic hybrid analogs of LHRH. The aim of this study was to determine the frequency of LHRHR expression in muscle invasive UC by immunohistochemistry. Methods Fifty-two cases, including TURBTs (31) and cystectomies (21), with at least muscle invasive UC were retrieved. Of 52 patients, 41 (78.8%) were male and 11 (21.1%) were female, with age ranging from 50 to 84 years. Immunohistochemical staining for LHRHR antibody (N-20, Santa Cruz, 1:50) was performed using the LSAB method. Membranous and/or granular cytoplasmic staining was considered as a positive reaction. Scoring was based on the percentage of positive tumor cells; negative (no staining), 1+ (1–25%), 2+ (26–50%), 3+ (51–75%), 4+ (> 75%). Results Of 52 UC cases, 32 (61%) were AJCC stage T2, 17 (33%) were T3, and 3 (6%) were T4. Of 52 cases, 30 (58%) were positive and 22 (42%) were negative for LHRHR. Of the 30 positive cases, 16 (53%) were scored 1+, 7 (23%) 2+, 5 (17%) 3+ and 2 (7%) 4 + . Conclusions More than half of the cases expressed LHRHR. Two-thirds of cases demonstrated focal (< 50%) immunoreactivity, which may cause false negative results in limited tissue samples. Immunohistochemical expression of LHRHR in UC can be a predictive marker for potential efficacy of LHRH cytotoxic hybrid analogs.

Keywords

• Muscle-invasive urothelial carcinoma
• Luteinizing hormone-releasing hormone receptors (LHRHR)
• LHRH cytotoxic hybrid analogs