Vascular growth patterns correlate with histological subtypes in human lung adenocarcinoma

Lung adenocarcinoma, the most common subtype of non-small cell lung cancer (NSCLC), exhibits diverse histopathological and vascular patterns influencing prognosis and therapeutic response. Angiogenesis, the process of new blood vessel formation, has historically been regarded as the predominant mechanism of tumor vascularization in solid cancers. However, vessel co-option, a non-angiogenic process, has emerged as an alternative strategy, involving the hijacking of pre-existing blood vessels by cancer cells rather than the induction of new ones. Furthermore, vessel co-option has been observed in both primary and metastatic cancers. The aim of this study was to determine the vascular patterns of different human adenocarcinoma samples and establish potential correlations between histological subtypes and microvascular growth patterns. Seventy lung adenocarcinoma samples were classified according to the 2021 WHO classification system, and their vascularization patterns were analyzed using CD31 immunohistochemistry and Weigert-Van Gieson staining. A substantial correlation was observed between histological subtypes and vascularization strategies, with solid basal and diffuse tumors exhibiting angiogenesis, and solid alveolar and lepidic tumors associated with vessel co-option. Additionally, papillary and micropapillary patterns exhibited mixed vascularization, while acinar tumors displayed the highest heterogeneity. The combination of staining techniques improved classification accuracy, achieving successful identification in 92.5% of cases. In conclusion, we present a powerful tool that can be used in lung cancer diagnostics to analyze tumor vascularization based on CD31 and elastic fibers staining. The observed correlations highlight the significance of histopathological assessment in determining vascularization mechanisms, which may optimize therapeutic strategies for NSCLC. HighlightsO_LIVascular patterns differ among histological subtypes in lung adenocarcinoma. C_LIO_LICD31 and WVG staining improves vascular pattern classification. C_LIO_LISolid basal and diffuse tumors show angiogenesis, whereas alveolar solid shows co-option. C_LIO_LIPapillary and micropapillary patterns display mixed angiogenic/co-option features. C_LIO_LIVascular profiling may guide NSCLC prognosis and anti-angiogenic therapy effectiveness. C_LI