J Cancer 2019; 10(15):3397-3406. doi:10.7150/jca.31231

Research Paper

Adjustment of Microvessel Area by Stromal Area to Improve Survival Prediction in Non-Small Cell Lung Cancer

Luo Fang1*, Ying He2*, Yujia Liu2*, Haiying Ding2, Yinghui Tong2, Luying Hu2, Canming Wang3, Yiwen Zhang2, Xiaowei Zheng2, Ping Huang2✉

1. Department of Pharmacy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
2. Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
3. Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
*L. Fang, Y. He and Y.J. Liu contributed equally to this work.

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Citation:
Fang L, He Y, Liu Y, Ding H, Tong Y, Hu L, Wang C, Zhang Y, Zheng X, Huang P. Adjustment of Microvessel Area by Stromal Area to Improve Survival Prediction in Non-Small Cell Lung Cancer. J Cancer 2019; 10(15):3397-3406. doi:10.7150/jca.31231. Available from http://www.jcancer.org/v10p3397.htm

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Abstract

Background: Sustained tumor growth and metastasis require sufficient blood supply, and microvessel area (MVA) has been reported that is related to prognosis of cancer patients. However, tumor cells may not be nourished enough by blood vessels when the cells are separated from vessels by thick stroma. Therefore we investigated whether stroma-area normalized MVA (SnMVA) is a more important prognostic factor than MVA.

Materials and Methods: 100 NSCLC patients who underwent resection between July 2011 and October 2012 were randomly selected. We determined the MVA of the tumor tissues by anti-CD31 immunostaining of microvessels. Stroma-area normalized MVA (SnMVA) was a ratio of MVA to stromal area. Correlation of MVA and SnMVA with overall survival (OS) or progression-free survival (PFS) was assessed using multivariate analysis.

Results: Median MVA was 0.0228 (range, 0.00393 to 0.172), and median SnMVA was 0.0441 × 10-6 (range, 0.00393 × 10-6 to 0.259 × 10-6). There was no significant difference in OS between groups of different MVA (HR 0.58, 95%CI 0.28 to 1.19, p = 0.148). In contrast, the risk of death was significantly decreased in high SnMVA group (at or below the median) than in group with low SnMVA (HR 0.47, 95%CI 0.23 to 0.97, p = 0.046). Furthermore, in multivariate analysis, high SnMVA, but not MVA, was an independent prognostic factor after adjusting for age, sex, tumor stage and other factors. OS was significantly associated with SnMVA in six of seven subgroup analysis, but with MVA in only three.

Conclusions: Our study showed that the NSCLC patients with high SnMVA had higher OS. And SnMVA is a prognostic factor with greater accuracy than MVA. Since stroma exists widely in a variety of cancer tissues, we infer that SnMVA may also predict the prognostic of other types of cancers.

Keywords: microvessel area, stromal area, non-small cell lung cancer, prognostic marker, stroma-area normalized mva