Clinicopathology of Early Gastric Carcinoma: An Update for Pathologists and Gastroenterologists

Abstract

Background: The WHO defines early gastric carcinoma (EGC) as invasive carcinoma up to the submucosal layer, regardless of nodal metastasis. The recent study results indicate that EGC varies in location, histology, nodal metastasis, and prognosis. Summary: The heterogeneity in EGC may be related to various types of epithelial stem cells. The most important stem cells include Lgr5⁺ cells at the base of a gastric unit in the antrum-pylorus-cardia, Mist1⁺ cells at the isthmus/Troy⁺ cells at the base in the corpus-fundus, and Sox2⁺ cells at the base in almost all regions. Dysregulation of these cells along with environmental factors transform stem cells in different regions into malignancy in genetically susceptible populations. Key Message: The 2 most vulnerable regions for EGC have been found along the lesser curvature: the cardia in elderly patients and antrum-angularis in mid-aged and elderly patients. Most hereditary early-onset gastric carcinomas are concentrated in the corpus-fundus of young women. By histology, the most common EGC type is tubular adenocarcinoma in many growth patterns, starting in the neck of a gastric unit. Worse prognosis has been found in early papillary, compared to tubular, adenocarcinoma, related to deeper penetration, more lymphovascular invasion, and more liver and nodal metastases. Contrary to the common belief, intramucosal signet ring cell carcinoma demonstrates low risk of nodal metastasis, comparable to early intestinal-type EGC. Practical Implications: The overall risk for nodal metastasis in EGC is low but significant. It is urgent to organize multicenter studies on risk of nodal metastasis in EGC in order to establish more reliable clinical practice guidelines to treat EGC patients.

ALDH1A3‐mTOR axis as a therapeutic target for anticancer drug‐tolerant persister cells in gastric cancer

“…To examine the alteration of gastric cancer cell populations upon treatment with anticancer drugs, we conducted single‐cell analysis for the expressions of gastric tissue lineage, stem cell and drug‐tolerant persister‐related genes. Gastric tissue consists of cells in various differentiation stages, including stem, progenitor, surface mucous, mucous gland and chief cells and endocrine cells, and specific markers for each cell type have been established (Figure A) . To induce persister cells, JSC15‐3 cells were treated with 3 µmol/L 5‐FU or 30 nmol/L SN38, an active metabolite of irinotecan, for 7 days and JSC17‐2 cells were treated with 3 µmol/L 5‐FU for 6 days.…”

“…Gastric tissue consists of cells in various differentiation stages, including stem, progenitor, surface mucous, mucous gland and chief cells and endocrine cells, and specific markers for each cell type have been established ( Figure 1A). [13][14][15][16][17][18][19] To induce persister cells, JSC15-3 cells were treated with 3 µmol/L 5-FU or 30 nmol/L SN38, an active metabolite of irinotecan, for 7 days and JSC17-2 cells were treated with 3 µmol/L 5-FU for 6 days. We focused on these two drugs because their prodrugs, capecitabine, tegafur and irinotecan, are commonly used for gastric cancer treatment in Japan.…”

“…Normal gastric tissue consists of various cell types that are differentiated from stem cells into progenitor cells and then surface mucous (pit), mucous gland (neck) and endocrine cells through multiple steps . Recent studies have revealed the gastric cell lineage and specific markers for each cell type (summarized in Figure A) . For example, LGR5 and TROY are gastric stem cell markers, whereas SOX9 is a progenitor cell marker.…”

“…[13][14][15] Recent studies have revealed the gastric cell lineage and specific markers for each cell type (summarized in Figure 1A). [13][14][15][16][17][18][19] For example, LGR5 and TROY are gastric stem cell markers, whereas SOX9 is a progenitor cell marker. MUC5AC, TFF1 and GKN1 mark pit cells, whereas MUC6 and TFF2 are hallmarks of neck cells.…”

The Prognostic Value of Mucin Immunohistochemical Profile of Early Gastric Cancer

“…Реже других желудочный , 22]. По литературным данным частота встречаемости желудочного иммунофенотипа при дифференцированном РРЖ колеблется от 7,9% до 23,9%[14,23] и даже может достигать 52,38%[9]. В нашем исследовании при дифференцированном типе РРЖ желудочный иммунофенотип встречался в 9,8% случаев (9/91), кишечный -в 47,2% (43/91).Важность исследования муцинового профиля РРЖ объясняется тем, что дифференцированный РРЖ (по классификации Nakamura K.), особенно диаметром менее 2 см, является общепринятым критерием в показаниях к эндоскопической резекции РРЖ, предложенной JGCA[4].…”