Perivascular cell coverage of intratumoral vasculature is a predictor for bevacizumab efficacy in metastatic colorectal cancer

Chang Jiang,1,* Yu-Hua Huang,2,* Jia-Bin Lu,2 Yuan-Zhong Yang,2 Hui-Lan Rao,2 Bei Zhang,1 Wen-Zhuo He,1 Liang-Ping Xia1 1VIP Region, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China *These authors contributed equally to this work Purpose: Tumor vessels supported by perivascular cells have been implicated in the failure of some anti-angiogenic agents. The relationship between perivascular cell coverage (PC) and bevacizumab efficacy in metastatic colorectal cancer (mCRC) was analyzed.Patients and methods: A total of 284 consecutive mCRC patients who received first-line chemotherapy with or without bevacizumab from 2007–2014 in Sun Yat-Sen University Cancer Center were analyzed. Immunohistochemical double-stain for the perivascular cell marker alpha-smooth muscle actin and endothelial cell (cluster of differentiation 31) was performed to characterize the intratumoral microvascular density. Multispectral image capturing and computerized image analyses were used to quantify the microvessels supported by the perivascular cells. The patients were divided into high and low PC group according to a median cutoff value of 0.55.Results: No significant differences in overall survival (OS) and progression-free survival (PFS) were noted between the high and low PC group. In the low PC group, the patients with bevacizumab treatment had favorable OS (P=0.03), but without PFS benefit. In the high PC group, neither OS nor PFS was significantly different between the B+C and C subgroup. Tumors with perineural invasion had high PC (P=0.03).Conclusion: The data showed that a low PC value could be a predictor for bevacizumab benefit. Keywords: perivascular cell coverage, bevacizumab, predictive marker, overall survival, metastatic colorectal cance