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. 2025 Jul 25:15:1481726.
doi: 10.3389/fonc.2025.1481726. eCollection 2025.

Vasculogenic mimicry in non-small cell lung cancer: a systematic review

Valeriia Shapkina #  1   2 , Vadim Shindyapin #  3   4 , Nikita Burlov #  5 , Elizaveta Prosekina #  6 , Anna Artemyeva #  6   7
Affiliations

Vasculogenic mimicry in non-small cell lung cancer: a systematic review

Valeriia Shapkina et al. Front Oncol. .

Abstract

Vasculogenic mimicry (VM), a non-endothelial tumor blood supply mechanism linked to poor prognosis in various cancers, requires consolidated prognostic evaluation in non-small cell lung cancer (NSCLC). This systematic review synthesized evidence on VM's association with survival outcomes (OS, DFS, PFS) in NSCLC patients. Following PRISMA-ScR guidelines, PubMed and Google Scholar were searched, identifying 19 eligible studies (all in Chinese populations) using immunohistochemistry (CD31/CD34-PAS) for VM detection. Eighteen studies found VM presence (prevalence 13.6%-45.2%) significantly associated with worse survival. Multivariate analyses identified VM as an independent negative prognostic factor, increasing mortality risk (HR 1.542-2.542) and progression risk (HR 2.1-2.4). However, critical limitations included exclusive focus on Asian cohorts, universal retrospective design, inconsistencies and potential artifacts in VM detection, and statistical issues (misreported risk measures, discordant data). While VM correlates with reduced survival in NSCLC, suggesting potential prognostic utility, these limitations - particularly ethnic homogeneity, retrospective bias, methodological heterogeneity, and statistical errors - preclude definitive conclusions. Future prospective studies with standardized VM assessment and diverse populations are essential for validation.

Keywords: histology; non-small cell lung cancer; prognosis; systematic review; vasculogenic mimicry.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study selection process. Created with http://www.BioRender.com.
Figure 2
Figure 2
Histological sample of NSCLC with VM: tubular type, PAS staining, 40x magnification. An arrow indicates PAS-positive tubular VM structures, demonstrating characteristic PAS reactivity in vasculogenic mimicry patterns.
Figure 3
Figure 3
Histological sample of NSCLC with VM: patterned matrix type, PAS staining, 40x magnification. An arrow highlights PAS-positive extracellular matrix sheets consistent with patterned matrix-type VM, demonstrating distinctive PAS reactivity in matrix-rich VM architectures.
Figure 4
Figure 4
Histological sample of NSCLC with blood vessels: IHC staining for CD31, 400x magnification. Brown chromogenic staining highlights the vascular endothelium.
Figure 5
Figure 5
VM in NSCLC, tubular type. Schematic representation. Created with http://www.BioRender.com.
Figure 6
Figure 6
VM in NSCLC, patterned matrix type. Schematic representation. Created with http://www.BioRender.com.
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