Flattened microvessel independently predicts poor prognosis of patients with non-small cell lung cancer

Abstract

Angiogenesis plays an essential role in improving tumor progression, whereas, its value in prognosis predicting remains controversial, especially in non-small cell lung cancer (NSCLC). Most recently, microvessel pattern has been raised as a novel prognosis factor. In this study, flattened microvessel, evaluated by tumor microvessel aspect ratio (TMAR), was conducted as a prognostic factor in NSCLC patients. A total of 100 patients with NSCLC were retrospectively reviewed. Microvessel in tumor was visualized by immunochemistry staining and then TMAR was determined. The prognostic role of TMAR was evaluated by univariate and multivariate analysis. Most of intratumor microvessels were flattened with a median TMAR of 3.65 (range, 2.43 - 6.28). Patients were stratified into high TMAR group (TMAR ≥ 3.6) and low TMAR group (TMAR < 3.6). Compared with subpopulation with low TMAR, high TMAR had significantly high risk of cancer-related death (univariate analysis: HR = 5.06, 95% CI: 2.44-10.47, p<0.001; multivariate analysis: HR = 4.53, 95% CI: 1.70-12.06, p=0.002).In conclusion, the results of our study demonstrate that flattened microvessel in tumor tissue is a promising prognosis predictor of NSCLC patients.

Keywords: aspect ratio; flattened microvessel; microvessel abnormality; non-small cell lung cancer (NSCLC); prognosis.

Figure 1. Tumor vascular patterns and TMAR values in NSCLC tissue specimens

A. Normal (left), slightly flattened (middle) and obviously flattened microvessels (right) positively immune-stained by CD31 (red triangle). Scale bar: 50 μm. B. Schematic representation of microvessel with various TMAR value (1^st Q: the first quartile value, 2^nd Q: the second quartile value, 3^rd Q: the third quartile value); C. TMAR values stratified by different clinicopathologic factors, including age, gender, smoking history, tumor histology, tumor differentiation, and disease stage.

Figure 2. Survival analysis

Kaplan-Meier curves of OS A. and PFS B. for high and low TMAR groups. C. Univariate and multivariate analysis of OS and PFS for TMAR and clinicopathologic factors.