Abstract 1711: Expression patterns of the G protein-coupled receptor, GPRC5A, in human malignant pleural mesothelioma

Abstract

Abstract The G protein-coupled receptor family C group 5 member A (hGPRC5A, mGprc5a) was previously shown to function as a lung-specific tumor suppressor gene evidenced by the development of lung adenomas and adenocarcinomas in mice with knockout of the gene. Moreover, we have demonstrated that the immunohistochemical expression of GPRC5A protein was significantly lower in non-small cell lung cancer (NSCLC) resected specimens compared to normal bronchial epithelia from healthy individuals. The latter findings prompted us to examine the expression patterns of GPRC5A in malignant pleural mesothelioma (MPM) because, like NSCLC, this malignancy develops in the thoracic cavity. Analysis of two publicly available MPM microarray datasets revealed that GPRC5A mRNA expression is significantly higher in MPMs compared to matched normal pleura (5.5 fold higher, p=0.002; 6.57 fold higher, p=0.04). GPRC5A immunohistochemical protein expression was semi-quantitatively assessed in formalin-fixed paraffin embedded (FFPE) MPM surgical specimens (n=73) comprised of 41 epitheloid, 14 biphasic and 18 sarcomatoid type MPMs. GPRC5A protein expression was also assessed in a subset of the MPM specimens (n=51) that were reconstructed as high-density spiral tissue microarrays (TMA) developed by J. Fukuoka and colleagues (Sakura-Finetek, Tokyo, Japan) comprised of 35 epitheloid, 9 biphasic and 7 sarcomatoid type MPMs. ANOVA analysis demonstrated significant differences in GPRC5A immunohistochemical expression among MPMs based on the histological subtype (p<10-6) with relative highest expression in the epitheloid tumors (mean, 98.04 ± 54.55; min, 0; max, 200), intermediate expression in biphasic-type tumors (mean, 53.57 ± 38.55; min, 0, max, 140) and lowest expression in sarcomatoid-type MPMs (mean, 24.44 ± 21.48; min, 0; max, 70). The patterns of GPRC5A expression based on histological type of surgical MPM specimens were corroborated using the spiral TMA technology with relative highest expression in the epitheloid tumors lowest expression in sarcomatoid-type MPMs. Importantly, GPRC5A immunohistochemical protein expression was positively significantly correlated between the surgical and spiral TMA specimens (R=0.71, p<10-6). We then sought to examine the association of GPRC5A expression with overall survival in MPM. GPRC5A expression was not associated with overall survival when all histological-type MPMs were included. Interestingly, patients with non-epitheloid type MPMs with relatively higher GPRC5A expression exhibited significantly worse overall survival compared to MPM patients with similar histology and lower expression (p=0.02 of the log-rank test). These findings suggest that GPRC5A may function as an oncogene in MPMs and warrant further studies to probe the function of this receptor in mesotheliomas. Supported by DoD PROSPECT grant W81XWH-07-1-0306. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1711. doi:1538-7445.AM2012-1711