The characteristics of tumor stroma and tumor microenvironment in the invasion process of intestinal-type gastric adenocarcinomas, and their relationship with L-Caldesmon and periostin

Objective: This study aimed to investigate the impact of the tumor microenvironment (TME), tumor budding (TB), stromal reactions, and tumor-associated macrophages on the prognosis of intestinal-type gastric adenocarcinomas. Additionally, the role of stromal markers L-Caldesmon (L-CaD) and Periostin in tumor assessment and their relationship with prognosis were evaluated. Materials and Methods: A retrospective analysis was conducted on 100 cases of gastric adenocarcinoma diagnosed between 2010 and 2020 at the Department of Pathology, Manisa Celal Bayar University Medical Faculty. Histopathological features, TB, the nature of desmoplastic stroma, immune markers related to TME (CD68, CD163), and stromal markers (L-CaD, Periostin) were analyzed using immunohistochemical (IHC) methods. Statistical analyses were performed using SPSS 23.0, and survival analyses were conducted using Cox regression tests. Results: The mean age of the 100 patients included in the study was 62.65 ± 11.89 years, with 69% being male. Among the tumors, 65% were proximally and 35% were distally located. Higher TB grades (TB 3) were significantly associated with increased rates of lymphovascular invasion (LVI), perineural invasion (PNI), and lymph node metastasis (LNM) (p<0.05). The CD163-positive macrophage ratio showed a positive correlation with tumor stage, while cases with intense lymphocytic response exhibited higher CD68 and CD163 expression levels (p<0.001). Periostin expression was found to be associated with tumor progression, with significant correlations observed between its invasive margin levels and CD68/CD163 expression (p<0.01). Conclusion: Tumor budding in gastric adenocarcinomas is associated with lymphovascular and perineural invasion, making it a significant prognostic marker. CD163-positive macrophages support an immunosuppressive microenvironment associated with tumor progression. Periostin appears to play a role in stromal interactions within the TME and tumor progression. These findings highlight the importance of considering TME components in the prognostic evaluation of gastric adenocarcinomas.