Histological diversity and molecular characteristics in gastric cancer: relation of cancer stem cell-related molecules and receptor tyrosine kinase molecules to mixed histological type and more histological patterns
Histological diversity and molecular characteristics in gastric cancer: relation of cancer stem cell-related molecules and receptor tyrosine kinase molecules to mixed histological type and more histological patterns
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DOI：
10.1007/s10120-020-01133-w
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发表时间：
2020-10-28
期刊：
影响因子：
7.4
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Sentani, Kazuhiro;Imai, Takeharu;Yasui, Wataru
背景胃癌（GCs）仍然是癌症相关死亡的主要原因之一。胃癌的组织学和分子特征可能在同一肿瘤的不同区域有很大差异。肿瘤内异质性一直被认为是有效诊断和成功分子治疗的主要障碍。方法对842例胃癌患者进行再评估，分析肿瘤内组织学形态的数量或组成与粘膜及侵袭区临床病理参数的关系。此外，我们还搜索了标记组织学多样性的gc相关分子或分子亚型。结果浸润区组织学数目较多或分型混合的胃癌患者T分级及分期明显高于浸润区胃癌患者，粘膜区胃癌患者T分级及分期无明显相关性。组织学多样性的胃癌预后较差，特征性表达肿瘤干细胞相关分子（CD44、CD133或ALDH1）和受体酪氨酸激酶分子（HER2、EGFR或c-MET），以及幽门螺杆菌感染。粘膜区CD44、HER2、c-MET、层粘连蛋白5、中心dot 2或保留的E-cadherin的表达预示着浸润区组织数量更多、类型混合。此外，GC的染色体不稳定性亚型与更多的组织学数目和混合组织学类型显著相关，而GC的基因组稳定性亚型与纯型显著相关。结论本研究揭示了胃癌的组织学多样性与分子特征之间的关系，希望能对胃癌的早期诊断、预防和有效治疗有所帮助。
Background Gastric cancers (GCs) are still one of the leading causes of cancer-related mortality. The histological and molecular features of GC may differ widely from area to area within the same tumor. Intratumoral heterogeneity has been considered a major obstacle to an efficient diagnosis and successful molecular treatment. Methods We selected and reevaluated 842 GC cases and analyzed the relationship between numbers or composites of histological patterns within tumors, and clinicopathological parameters in mucosal and invasive areas. In addition, we searched for the GC-associated molecules or molecular subtypes marking histological diversities. Results GC cases with more histological numbers or mixed types in invasive areas showed significantly higher T grade and staging, whereas those in mucosal areas did not show any significant associations. GCs with histological diversities showed poorer prognosis and characteristically expressed cancer stem cell-related molecules (CD44, CD133 or ALDH1) and receptor tyrosine kinase molecules (HER2, EGFR or c-MET) as well as Helicobacter pylori infection. Expressions of CD44, HER2, c-MET, laminin 5 center dot 2 or retained E-cadherin in mucosal areas were predictive of more histological numbers and mixed types in invasive areas. In addition, the chromosomal instability subtype of GC showed significant associations with more histological numbers and mixed histological type, whereas the genomic stability subtype of GC showed a significant relationship with pure type. Conclusions We displayed the relationship between histological diversity and molecular features in GC, and we hope that the present data can contribute to the early diagnosis and prevention, and effective treatment of GC.