Abstract 326P
Background
Pulmonary neuroendocrine tumors (PNETs) account for about 20% of lung cancer cases and include small cell lung carcinomas (SCLC), large cell neuroendocrine carcinomas (LCNEC), atypical carcinoids, and typical carcinoids (TC). The extracellular matrix (ECM) is essential in regulating cell behavior, but its role in PNETs aggressiveness is not well clarified. Further, the epithelial-mesenchymal transition (EMT) is critical for cancer progression and metastasis, enhancing malignancy through interactions with ECM components.
Methods
We analyzed 38 surgically resected, formalin-fixed, paraffinembedded samples of SCLC (N=33), LCNEC (N=3), and AC (N=2). The expression levels of ECM and EMT-related proteins were detected using immunohistochemistry and quantified with QuPath software.
Results
Our results revealed high expression of COL5A2, COL3A1, ITGB1, and CDH1, whereas CDH2 and ZEB1 showed expression levels below the median in most cases. Notably, ITGA5 expression was negative in 94.7% of patients. No significant correlation was found between markers and clinicopathological features. However, we identified positive correlations between ITGB1 and CDH1 (ρ=0.21; p=0.05), ITGB1 and CDH2 (ρ=0.40; p < 0.01), COL3A1 and COL5A2 (ρ=0.23; p=0.03), and CDH1 and CDH2 (ρ=0.31; p=0.05). Our study revealed high CDH1 expression in 57.9% of patients, compared to just 7.9% for N-cadherin (CDH2), indicating that PNETs, similar to other invasive carcinomas, retain epithelial markers during metastasis. ECM remodeling by COL3A2, COL5A2, and ITGB1 supports CDH1 expression, preserving cohesive tumor cell clusters. A multivariate Cox regression analysis identified age, along with the expression levels of COL3A1, ITGB1, and CDH2, as independent prognostic factors for overall survival (OS), with younger patients and those with high levels of these markers having poorer OS rates.
Conclusions
We hypothesize that the interaction between the ECM and EMT factors is essential for tumor progression in PNETs, and also that cancer cells invade the surrounding stroma in cohesive clusters, connected by CDH1, which enhances invasion and metastasis, affecting patient survival.
Legal entity responsible for the study
The authors.
Funding
Sao Paulo Research Foundation (2018/20403-6, 2023/02755-0, 2023/09682-9; 2023/01158-9), The National Council for Scientific and Technological Development (303735/2021-0; 151118/2023-0).
Disclosure
All authors have declared no conflicts of interest.