Fujibayashi Seito, Kobayashi Kazuhiro, Tomita Hiroyuki, Watanabe Daichi, Endo Masahide, Yokoi Ryoma, Matsumoto Keita, Hayashi Hirokatsu, Kuno Masashi, Fukada Masahiro, Yasufuku Itaru, Sato Yuta, Asai Ryuichi, Tajima Jesse Yu, Hara Akira, Matsuhashi Nobuhisa
Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Oncol Lett. 2025 Aug 12;30(4):479. doi: 10.3892/ol.2025.15224. eCollection 2025 Oct.
The histological classification of gastric adenocarcinoma influences its prognostic outcomes and therapeutic strategies. Although fibroblast growth factor (FGF)10 is important for gastric morphogenesis, its use as a molecular marker of gland-forming differentiation pattern remains undefined. The present study examined 117 surgically resected gastric adenocarcinoma specimens using immunohistochemical analysis to evaluate the expression of FGF10 and FGF receptor 2 (FGFR2). Expression patterns in tumor cells and the surrounding stroma were assessed using a four-tier scale. Associations between marker expression and histological differentiation were analyzed by multivariable ordinal logistic regression, adjusting for age, human epidermal growth factor receptor 2 and epidermal growth factor receptor status. Elevated FGF10 expression was significantly associated with well-differentiated, gland-forming histological subtypes, particularly in moderately differentiated tubular adenocarcinoma [adjusted odds ratio (OR) in tumor cells: 1.749, 95% confidence interval (CI) 1.231-2.487, P=0.002; adjusted OR in stroma: 2.418, 95% CI 1.123-5.206, P=0.024]. Conversely, FGFR2 expression showed no association with differentiation pattern (adjusted OR: 0.908, 95% CI 0.452-1.824, P=0.788). Survival analysis revealed no significant relationship between FGF10 or FGFR2 expression level and overall patient survival [hazard ratio (HR) for FGF10 in tumor cells: 0.823, 95% CI 0.640-1.057, P=0.127; HR for FGF10 in stroma: 0.675, 95% CI 0.385-1.183, P=0.170; HR for FGFR2 in tumor cells: 1.080, 95% CI 0.559-2.085, P=0.819]. FGF10 may thus be a promising molecular marker of gland-forming differentiation pattern in gastric adenocarcinoma, offering valuable insights for refining its histopathological classification. These findings may contribute to the development of stratification biomarkers for personalized therapeutic approaches, particularly for the selection of molecular-targeted therapies. The absence of an association with overall survival, however, highlights the need for further investigations into the underlying mechanisms and their broader clinical significance.
胃腺癌的组织学分类会影响其预后结果和治疗策略。尽管成纤维细胞生长因子(FGF)10对胃形态发生很重要,但其作为腺形成分化模式分子标志物的用途仍不明确。本研究使用免疫组织化学分析检查了117例手术切除的胃腺癌标本,以评估FGF10和成纤维细胞生长因子受体2(FGFR2)的表达。使用四级量表评估肿瘤细胞和周围基质中的表达模式。通过多变量有序逻辑回归分析标志物表达与组织学分化之间的关联,并对年龄、人表皮生长因子受体2和表皮生长因子受体状态进行校正。FGF10表达升高与高分化、腺形成组织学亚型显著相关,特别是在中分化管状腺癌中[肿瘤细胞中的校正比值比(OR):1.749,95%置信区间(CI)1.231 - 2.487,P = 0.002;基质中的校正OR:2.418,95%CI 1.123 - 5.206,P = 0.024]。相反,FGFR2表达与分化模式无关(校正OR:0.908,95%CI 0.452 - 1.824,P = 0.788)。生存分析显示,FGF10或FGFR2表达水平与患者总生存期之间无显著关系[肿瘤细胞中FGF10的风险比(HR):0.823,95%CI 0.640 - 1.057,P = 0.127;基质中FGF10的HR:0.675,95%CI 0.385 - 1.183,P = 0.十七;肿瘤细胞中FGFR2的HR:1.080,95%CI 0.559 - 2.085,P = 0.819]。因此,FGF10可能是胃腺癌腺形成分化模式的一个有前景的分子标志物,为完善其组织病理学分类提供有价值的见解。这些发现可能有助于开发分层生物标志物以用于个性化治疗方法,特别是用于分子靶向治疗的选择。然而,与总生存期无关联这一点凸显了需要进一步研究其潜在机制及其更广泛的临床意义。