Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. May 24, 2024; 15(5): 614-634
Published online May 24, 2024. doi: 10.5306/wjco.v15.i5.614
Different types of tumor microvessels in stage I-IIIA squamous cell lung cancer and their clinical significance
Marina A Senchukova, Evgeniy A Kalinin, Nadezhda N Volchenko
Marina A Senchukova, Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
Evgeniy A Kalinin, Department of Thoracic Surgery, Orenburg Regional Cancer Clinic, Orenburg 460021, Russia
Nadezhda N Volchenko, Department of Pathology, PA Hertzen Moscow Oncology Research Centre, Branch of National Medical Research Radiological Center, Moscow 125284, Russia
Author contributions: Senchukova MA designed and performed the research, and wrote the paper; Kalinin EA acquired and analyzed the data and contributed substantially to the conception and design of the study; Volchenko NN participated in the discussion of related data and revised and approved the final version; All the authors wrote and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Orenburg State Medical University (Russia, Orenburg), No. 281, dated 30 September 2021.
Informed consent statement: Patients were not required to give informed consent to the study because the study was retrospective and analyses were performed with anonymous clinical data obtained after each patient agreed to treatment via written consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data from patients included in the study in Statistica10 table or Excel table format can be provided upon request to the corresponding author at masenchukova@yandex.com.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marina A Senchukova, MD, PhD, Professor, Department of Oncology, Orenburg State Medical University, Sovetskaya Street 6, Orenburg 460000, Russia. masenchukova@yandex.com
Received: December 27, 2023
Peer-review started: December 27, 2023
First decision: January 17, 2024
Revised: February 12, 2024
Accepted: March 28, 2024
Article in press: March 28, 2024
Published online: May 24, 2024
Processing time: 145 Days and 19.3 Hours
Abstract
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 P < 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 (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the tumor solid component (P = 0.023) and fragmentation in the tumor solid component (P = 0.009), whereas the independent predictors of LUSC recurrence were tumor grade 3 (G3) (P = 0.001), stage N2 (P = 0.016), the presence of LFFCT in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001), and the absence of tumor spread through the AASs (P = 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.

Keywords: Lung cancer; Lung squamous cell carcinoma; Tumor microvessels; Tumor stroma; Regional lymph node metastases; Disease recurrence; Disease prognosis

Core Tip: In this retrospective study, we examined the morphology of different types of tumor microvessels, tumor parenchyma, and tumor stroma and their associations with the risk of regional metastasis and disease recurrence in lung squamous cell carcinoma (LUSC) patients. Independent predictors of LUSC metastases in regional lymph nodes were the central location of the tumor (P < 0.00001), the presence of retraction clefts (P = 0.003), capillaries in the solid component of the tumor (P = 0.023) and fragmentation of the solid component of the tumor (P = 0.009), while independent predictors of LUSC recurrence were tumor grade 3 (P = 0.001), N2 stage (P = 0.016), the presence of loose fine fibrous connective tissue in the tumor stroma (P < 0.00001), fragmentation of the tumor solid component (P = 0.0001) and the absence of tumor spread through the alveolar air spaces (P = 0.0083). These findings may help improve the diagnosis and treatment of LUSC.