Sasaki Y, Hayashi K, Suzuki T, Toyoshima A, Teragawa M, Gouda S, Amimoto K, Matsui S, Yamane Y, Chen H L, Ohara N, Teramoto N, Akagi T
Division of Pathology Jyuzen General Hospital, Niihama.
Rinsho Byori. 1996 Dec;44(12):1196-200.
Recently, clonal EBV-DNA and/or EBV-encoded small RNA(EBER1) have been detected in some gastric carcinomas. We reported the first observation of EBV infection in gastric glands with intestinal metaplasia, and characterized the EBV-infected lymphocytes which infiltrated in gastric mucosa. To determine the cellular location of EBV, EBER1 in situ hybridization(ISH) with an EBER1 oligonucleotide probe was applied to paraffin sections of the non-neoplastic gastric mucosa in 80 cases of gastric carcinoma and 49 cases of gastric ulcer. Not only was EBER1 expression detected in the nucleus of gastric cancer cells(5 cases) but also in non-neoplastic gastric epithelial cells(3 cases) and in infiltrated lymphocytes(40 cases). A single or a few shedding non-neoplastic epithelial cells in 2 cases of EBV-associated gastric cancer showed EBER1 expression. In one case, EBER1 was observed in all of the epithelial cells of a few gastric glands with intestinal metaplasia, suggesting that the stem cells of the metaplastic gastric glands were infected with EBV. EBV DNA was also detected in the EBER1-positive metaplastic glands scratched from the paraffin section by a single cell PCR method with a BamHI W primer pair. However, immunohistochemical examination showed that these metaplastic glands lacked expression of EBNA2 and LMP-1. The observation of these rare EBV-infected metaplastic glands reinforces the pre-transformation EBV infection hypothesis for EBV-associated gastric carcinoma. The double staining using ISH and immunohistochemistry revealed that EBER1 positive lymphocytes showed a B cell marker of L26(< 50%) but not T cell markers of UCHL1 and OPD4.
最近,在一些胃癌中检测到了克隆性EBV-DNA和/或EBV编码的小RNA(EBER1)。我们首次报道了在肠化生的胃腺中观察到EBV感染,并对浸润于胃黏膜的EBV感染淋巴细胞进行了特征描述。为确定EBV的细胞定位,我们将EBER1寡核苷酸探针原位杂交(ISH)应用于80例胃癌和49例胃溃疡患者的非肿瘤性胃黏膜石蜡切片。不仅在胃癌细胞(5例)的细胞核中检测到EBER1表达,在非肿瘤性胃上皮细胞(3例)和浸润淋巴细胞(40例)中也检测到了EBER1表达。2例EBV相关胃癌中单个或少数几个脱落的非肿瘤性上皮细胞显示EBER1表达。在1例中,在少数几个肠化生胃腺的所有上皮细胞中均观察到EBER1,提示化生胃腺的干细胞被EBV感染。通过使用BamHI W引物对的单细胞PCR方法,还在从石蜡切片刮取的EBER1阳性化生腺中检测到了EBV DNA。然而,免疫组化检查显示这些化生腺缺乏EBNA2和LMP-1的表达。这些罕见的EBV感染化生腺的观察结果强化了EBV相关胃癌的转化前EBV感染假说。ISH和免疫组化双重染色显示,EBER1阳性淋巴细胞显示L26的B细胞标志物(<50%),但不显示UCHL1和OPD4的T细胞标志物。