Different Types of Tumor Microvessels in Stage I-IIIA Squamous Cell Lung Cancer and Their Clinical Significance

Background: Lung cancer (LC) is the leading cause of morbidity and mortality among malignant neoplasms. Improving the diagnosis and treatment of LC remains an urgent task of modern oncology. Previously, we established that in gastric, breast and cervical cancer, tumor microvessels (MVs) differ in morphology and have different prognostic significance. The connection between different types of tumor MVs and the progression of LC is not well understood.

Aim: To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma (LUSC).

Methods: A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts, respectively. All patients underwent radical surgery (R0) at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021. Tumor sections were routinely processed, and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34 (CD34), podoplanin, Snail and hypoxia-inducible factor-1 alpha were performed. The morphological features of different types of tumor MVs, tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis. Statistical analysis was performed using Statistica 10.0 software. Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes (RLNs) and disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence. The effectiveness of the predictive models was assessed by the area under the curve. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. A value of < 0.05 was considered to indicate statistical significance.

Results: Depending on the morphology, we classified tumor vessels into the following types: normal MVs, dilated capillaries (DCs), atypical DCs, DCs with weak expression of CD34, "contact-type" DCs, structures with partial endothelial linings, capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates. We also evaluated the presence of loose, fine fibrous connective tissue (LFFCT) and retraction clefts in the tumor stroma, tumor spread into the alveolar air spaces (AASs) and fragmentation of the tumor solid component. According to multivariate analysis, the independent predictors of LUSC metastasis in RLNs were central tumor location ( < 0.00001), the presence of retraction clefts ( = 0.003), capillaries in the tumor solid component ( = 0.023) and fragmentation in the tumor solid component ( = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) ( = 0.001), stage N2 ( = 0.016), the presence of LFFCT in the tumor stroma ( < 0.00001), fragmentation of the tumor solid component ( = 0.0001), and the absence of tumor spread through the AASs ( = 0.0083).

Conclusion: The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.