Immunohistochemical analysis of Sonic Hedgehog in gastric adenocarcinoma and the relationship between mucin and HER2 expressions: Gastric adenocarcinoma

Bayram Yılmaz; Neşe  Çallı Demikan

doi:10.5281/zenodo.11046596

Authors

Bayram Yılmaz Hitit University Erol Olçok Training and Research Hospital, Department of Pathology, Çorum, Turkey https://orcid.org/0000-0002-1737-9446
Neşe Çallı Demikan Pamukkale University Faculty of Medicine, Department of Pathology, Denizli, Turkey https://orcid.org/0000-0001-5860-100X

DOI:

https://doi.org/10.5281/zenodo.11046596

Keywords:

Gastric adenocarcinoma, mucins, Sonic Hedgehog, human epidermal growth factor receptor-2

Abstract

Objective: Most of the gastric adenocarcinomas are still recognized in advanced stages despite the improvements in diagnostic methods. Inhibition of the SHH pathway is predicted to be a targeted therapy in advanced gastric adenocarcinomas. Determining the relationship of the SHH pathway with other prognostic markers in gastric cancers is being investigated in terms of patient management. This study aimed to investigate the relationship between Sonic Hedgehog (SHH) and mucin core proteins (MUCs) antibody expressions with prognosis and Human epidermal growth factor receptor-2 (HER2) levels in gastric adenocarcinomas.

Methods: Eighty-six patients diagnosed with gastric adenocarcinoma in surgical resection material between 2008-2014 were included in the study. The clinicopathological findings of the cases were recorded from hospital documents. Pathologic diagnoses were reclassified based on WHO (2019) classifications. An examination of MUC1, MUC2, MUC5AC, MUC6, SHH, and HER2 antibodies was performed immunohistochemically. The tissue microarray technique was used in the study. The clinicopathological findings were statistically evaluated by comparing them with the immunohistochemical findings and survival.

Results: The study found that tumor diameter, lymphovascular embolus, perineural invasion, lymph node metastasis, and tumor depth had a statistically significant impact on survival. Additionally, the immunohistochemical examination showed no correlation between SHH, mucin antibodies, and HER2 scores with survival. According to our results, HER2 overexpression was associated with MUC1 to luminal staining (p=0.0001). When HER2 expression and SHH expressions were compared, all cases with HER2 overexpression were found to be positive with SHH (p=0.03). This is the first study to determine the relationship between SHH, MUC1, and HER2 immunohistochemical expressions in gastric adenocarcinomas.

Conclusion: Examining the HER2 relationship between SHH and MUC1 expressions we have shown, with future genetic and molecular studies, will provide an understanding of different malignancy pathways in gastric adenocarcinomas.

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