Abstract 774: Anti-Müllerian hormone type II receptor (AMHRII) found expressed in human non-gynecological solid tumors, suggesting potential broader applications for anti-AMHRII-based therapy

Abstract

Abstract The anti-Müllerian hormone (AMH) belongs to the TGF-β family and plays a key role during fetal sexual development. It has been shown that AMH inhibits proliferation and induces apoptosis of AMH type II receptor (AMHRII) -positive tumor cells, especially progenitor cancer cells. Moreover, various reports have described the expression of AMHRII in human gynecologic cancers including ovarian tumors. Based on qRT-PCR test results, which were confirmed by a specific In-Situ Hybridization (ISH) assay, AMHRII mRNA could be detected only in normal ovary, testis and adrenal gland tissue, and at lower levels in pancreas and stomach. However, when a tissue microarray of solid tumor samples was tested with ISH assay, AMHRII mRNA was surprisingly detected in several primary cancer tissues including melanoma, lung, head and neck, colorectal and breast cancers. For example, a large ISH study involving 58 colorectal cancer samples demonstrated AMHRII expression in 55% of cases. AMHRII protein expression was confirmed by ImmunoHistoChemistry (IHC) in gynecological cancer samples including 179 out of 210 (85%) Granulosa Cell Tumor samples and 55 out of 80 (69 %) Epithelial Ovarian Cancers. In patients with gynecological cancers pre-screened by IHC for inclusion in a Phase Ia/Ib clinical trial of GM102, an anti-AMHRII monoclonal antibody, AMHRII positive membrane expression was detected in 116 out of 166 (70%) archived tumor tissues. Using the same IHC protocol, over 1000 frozen samples covering 16 different cancer types were tested, which demonstrated AMHRII expression in over 50% of hepatocarcinoma, colorectal, lung and renal cancer samples. No AMHRII expression was observed in 75 neuroendocrine lung tumor samples nor in 18 non-Hodgkin lymphoma samples tested. On a small panel of frozen ovarian (11) and colorectal (9) cancer samples using an immunofluorescence assay with an AlexaFluor488-conjugated GM102 antibody, AMHRII expression was confirmed on the matching fresh tissue samples, previously detected by IHC in their fixed counterpart samples. Preliminary FACS analysis of fresh ovarian and colorectal tumor samples have demonstrated comparable expression levels with mean values of 50,000 and 40,000 AMHRII receptors per cell, respectively. In conclusion, the results presented above, using a variety of detection methods and systems, have consistently shown that AMHRII is expressed in many different histological types of solid tumors. These results suggest that this embryonic receptor could be a suitable target for selective antitumor agents such as GM102. Citation Format: Jean-Marc M. Barret, Didier Meseure, Guillaume Bataillon, Noora Andersson, Aurélie Auguste, Olivier Dubreuil, Anniina Färkkilä, Emeline Perrial, Celine Bossard, Emily Loison, Anne Jarry, André Nicolas, Fanny Lemée, Solenne Gaillard, Mehdi Lahmar, Mikko Anttonen, Gabriel Champenois, Charles Dumontet, Isabelle Ray-Coquard, Alexandra Leary, Isabelle Tabah-Fisch, Anne Vincent-Salomon, Jean-François F. Prost. Anti-Müllerian hormone type II receptor (AMHRII) found expressed in human non-gynecological solid tumors, suggesting potential broader applications for anti-AMHRII-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 774.