Ichinoe M, Mikami T, Shiraishi H, Okayasu I
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan.
Histopathology. 2004 Dec;45(6):612-8. doi: 10.1111/j.1365-2559.2004.02031.x.
Early gastric carcinomas have two characteristic growth types, superficial spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and lower p21(WAF1/CIP1) expression and submucosal low proliferative activity have been shown in the former, compared with the latter. In order to cast light on whether angiogenesis contributes to these growth patterns, the present immunohistochemical study was performed with cancer tissues.
Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal invasive carcinoma cases were immunohistochemically compared. CD34 positivity, microvascular density (MVD), and expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX-2) were higher in cancer cells in both mucosal and submucosal layers in PEN than in SUP (P < 0.05). Submucosal MVD in PEN type was greater (P < 0.01) in cases with high than with low Ki67 labelling. Significant correlations were shown between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN type, but only a weak correlation between iNOS and COX-2 expression was evident with the SUP type.
Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.
早期胃癌有两种特征性生长类型,即浅表扩散型(SUP)和浸润型(PEN)。与后者相比,前者显示出更高的黏膜凋亡活性、更低的p21(WAF1/CIP1)表达以及黏膜下低增殖活性。为了阐明血管生成是否有助于这些生长模式,本研究对癌组织进行了免疫组织化学研究。
在总共807例早期胃癌中,对30例浸润型和33例浅表扩散型黏膜下浸润癌病例进行了免疫组织化学比较。浸润型癌的黏膜层和黏膜下层癌细胞中CD34阳性、微血管密度(MVD)、血管内皮生长因子(VEGF)和诱导型一氧化氮合酶(iNOS)的表达,但不包括环氧合酶2(COX-2)的表达均高于浅表扩散型(P<0.05)。浸润型病例中,Ki67标记高的病例黏膜下MVD大于标记低的病例(P<0.01)。浸润型中,MVD与VEGF、iNOS与COX-2以及VEGF与iNOS表达之间存在显著相关性,但浅表扩散型中iNOS与COX-2表达之间仅存在微弱相关性。
浸润型中MVD增加与血管生成因子、高VEGF和iNOS表达密切相关。相比之下,浅表扩散型具有低血管生成的特征。