Taniguchi Yoshiaki, Kiyozawa Daisuke, Kohashi Kenichi, Kawatoko Shinichiro, Yamamoto Takeo, Torisu Takehiro, Yoshizumi Tomoharu, Nakamura Masafumi, Kitazono Takanari, Oda Yoshinao
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan.
Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Gastric Cancer. 2025 Jan;28(1):41-50. doi: 10.1007/s10120-024-01562-x. Epub 2024 Nov 3.
Hepatoid adenocarcinoma of the stomach (HAS), a subtype of gastric cancer (GC), includes multiple tumor components, such as enteroblastic and tubular adenocarcinoma components. However, which component mostly contributes to the aggressive behavior of HAS remains unclear. Moreover, the role of tumor-associated macrophages (TAMs) has not been explored in HAS. This study evaluated the clinical significance of the proportion of the hepatoid component within the tumor, CD163 + macrophages, and macrophage colony-stimulating factor-1 (CSF-1) in HAS.
In total, 56 cases of primary HAS were analyzed. In each case, hepatoid (HC), enteroblastic (EC), and tubular (TC) components were identified, and the ratio of HC to the entire tumor (hepatoid component ratio, HCR) was assessed to examine the correlation between HCR and clinicopathological features. Immunohistochemical staining for CD163 and CSF-1 was performed, and differences in immunohistochemical results among the three tumor components were analyzed. In each tumor component, the prognostic impact of CD163 and CSF-1 was examined.
A high HCR was associated with worse overall survival (OS). CD163 + TAMs and CSF-1 immunoreactivity score in HC were significantly higher than those in the other components. High infiltration of CD163 + TAMs and a high CSF-1 immunoreactivity score in HC were associated with an aggressive course and worse OS. Multivariate analysis revealed the proportion of HC in HAS as an independent prognostic factor (HR = 3.176, p = 0.006).
The HCR and CD163 + TAMs may be useful prognostic predictors, and TAMs may be novel therapeutic targets of HAS.
胃肝样腺癌（HAS）是胃癌（GC）的一种亚型，包含多种肿瘤成分，如胚胎性和管状腺癌成分。然而，哪种成分对HAS的侵袭性行为贡献最大仍不清楚。此外，肿瘤相关巨噬细胞（TAM）在HAS中的作用尚未得到研究。本研究评估了肿瘤内肝样成分比例、CD163 +巨噬细胞和巨噬细胞集落刺激因子-1（CSF-1）在HAS中的临床意义。
共分析56例原发性HAS病例。在每个病例中，确定肝样（HC）、胚胎性（EC）和管状（TC）成分，并评估HC与整个肿瘤的比例（肝样成分比例，HCR），以检查HCR与临床病理特征之间的相关性。进行CD163和CSF-1的免疫组织化学染色，并分析三种肿瘤成分之间免疫组织化学结果的差异。在每个肿瘤成分中，检查CD163和CSF-1的预后影响。
高HCR与较差的总生存期（OS）相关。HC中的CD163 + TAM和CSF-1免疫反应性评分显著高于其他成分。HC中CD163 + TAM的高浸润和高CSF-1免疫反应性评分与侵袭性病程和较差的OS相关。多变量分析显示HAS中HC的比例是一个独立的预后因素（HR = 3.176，p = 0.006）。
HCR和CD163 + TAM可能是有用的预后预测指标，TAM可能是HAS的新型治疗靶点。
