Prognostic value of microvessel density in esophageal squamous cell carcinoma-a systematic review and meta-analysis

Angiogenesis produced by tumor microenvironment is play an important role in development of esophageal squamous cell carcinoma (ESCC). As a quantitative index of angiogenesis, literature has emerged contradictory results about the prognostic role of microvessel density (MVD) in ESCC. The aim of the study was to explore the impact of the correlation between MVD and the prognosis of ESCC based the published evidence. Pubmed and Web of science database were screened for the relationship of MVD with prognostic feature in ESCC up to March, 2021. 11 relevant articles were used for meta-analysis. The following data were extracted from the literature: author, year, country, the patients number of high/low MVD, tumor-node-metastasis (TNM) classification, clinical stage, lymphoid infiltrates, vessel invasion, invasive depth, differential degree and survival rate. The hazard ratio (HR) and odds ratios (OR) with 95% CI were used to assess the associations between MVD and overall survival (OS). Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p < 0.05). Egger test was used to calculate the publication bias. Subgroup analysis was stratified by antibody, region, sample capacity to explore the source of heterogeneity. 11 studies with 1055 patients were analyzed. Our results suggested that high MVD is an important factor to advanced TNM classification and clinical stage, and the high MVD is positive correlation with the lymph node invasion and vascular invasion(p < 0.05) in ESCC, but irrelevant to poor differential and invasive depth(p > 0.05). The result also indicated that low MVD is a benefit factor to prolong the survival rate (p < 0.05). And the source of the heterogeneity maybe is that the antibody used to detect the MVD was not consistent, patient number was not large enough and the count method on MVD. Across multiple studies, high MVD is correlated with clinicopathological criteria of poor prognosis and survival in ESCC. MVD could be the quantitative index to reactive angiogenesis and may play a pivotal role in ESCC development and progression. MVD may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment.