Abstract A126: Immunohistochemical analysis of integrin αv families in solid tumors

Abstract

Abstract Introduction: αv integrins are a class of adhesion molecules which play a role in tumor progression and metastasis, and have been found to be highly expressed in various cancer types. A phase I/II study of anti-αv integrin antibody Abituzumab showed prolonged overall survival in the subgroup of colorectal cancer (CRC) patients, in which tumor highly expressed αvß6. Here, we examined the expression of integrins in surgical resected specimens by immunohistochemistry and evaluated the relationship between integrin expression and clinicopathological features of Japanese patients with types of cancers which show high prevalence in Asian countries. Materials and methods: Immunohistochemical (IHC) staining for integrin αvβ3, αvβ5, αvβ6, αvβ8, pan-αv, and CD31 was conducted for formalin fixed paraffin embedded surgical specimen of Japanese patients with five different types of cancers, including gastric cancer (GC), esophageal squamous cell cancer (ESCC), biliary tract cancer (BTC), hepatocellular carcinoma (HCC), and CRC. All samples were collected at the National Cancer Research Center Hospital East between 2000 and 2014. The total number of samples was 250. Fifty samples of each cancer type were examined. IHC staining of each sample was evaluated by pathologists. Histoscores (H-score; range: 0 - 300) were used to describe the intensity and prevalence of signal. H-scores were determined separately for membrane and cytoplasm, both in tumor cells and normal adjacent cells. Results: Pan-αv expression patterns were found in most tumor cells of all tumor entities with a tendency towards moderate or strong staining. Expression of αvβ6 was observed in tumor cells of all tumor types other than HCC. Especially, BTC and ESCC tumor cells showed elevated intensity and higher prevalence of αvβ6 expression both in membranous and cytoplasmic compared to CRC tumor samples. In addition, BTC and ESCC tumor cells showed stronger intensity and higher proportion of αvβ6 compared to normal tissues. In CRC, the cases with higher expression of αvβ6 showed stronger tumor invasion or lymph node metastasis. In BTC and ESCC, high expression of αvβ6 was detected regardless of T-stage or lymph node metastasis status. ESCC cases with high expression of αvβ6 had a poor prognosis compared to cases with low expression. Conclusions: These data demonstrated that the expression of αvβ6 integrin correlated with clinicopathological features of BTC, ESCC, and CRC. High expression of αvβ6 in ESCC was associated with the poor prognosis. These data indicate that αv integrin may be an attractive target in cancer treatment. Citation Format: Yasutoshi Kuboki, Yuka Nakamura, Takeshi Kuwata, Satoshi Fujii, Motohiro Kojima, Toshio Kuronita, Morihiro Watanabe, Josef Straub, Atsushi Ochiai. Immunohistochemical analysis of integrin αv families in solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A126.