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Cancer. 1994 Oct 15;74(8):2245-50.

Tumor angiogenesis in human lung adenocarcinoma.

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First Department of Medicine, School of Medicine, Hokkaido University, Japan.



Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma.


Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200x field (0.723 mm2) in the most active areas of neovascularization.


The microvessel counts from patients with relapse after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other.


Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.

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