Montone K T, Tomaszewski J E
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia.
J Clin Lab Anal. 1993;7(3):188-95. doi: 10.1002/jcla.1860070310.
We examined prostatic adenocarcinomas from 19 formalin fixed radical prostatectomy specimens for EGFR by in situ hybridization employing a 24 base synthetic biotin-labeled oligonucleotide probe complementary to the 5' end of EGFR mRNA. All slides were examined by light microscopy using a 25x objective. Each field was given three values: 1) Gleason grade (1-5), 2) Nuclear grade [small (< 5.0 mu), intermediate (5-10 mu), large (> 10 mu)], and 3) EGFR staining intensity score (0, absent; 1, weak; 2+, moderate to strong). A total 851 25x fields of prostatic adenocarcinoma were studied. All cancers demonstrated at least some degree of cytoplasmic EGFR message. The EGFR intensity score correlated best with tumor nuclear size. No correlation with Gleason grade was observed. Cytoplasmic staining was also identified in the basal cell layer of benign glands, high grade prostatic intraepithelial neoplasia, stromal nodules, transitional epithelium, periurethral glands, and ganglion cells. Competitive hybridization experiments using an unlabeled EGFR probe showed markedly diminished hybridization signal, while in situ hybridization with a biotin-labeled EGFR sense probe was negative. Immunohistochemistry on 13 of the tumors with 2 monoclonal antibodies against EGFR showed staining in only 1/13 and 10/13 tumors. EGFR expression appears to be most prominent in tumors of high nuclear grade. Further studies will be necessary to explore this growth factor as a prognostic variable in this tumor.
我们采用与表皮生长因子受体(EGFR)mRNA 5'端互补的24个碱基的合成生物素标记寡核苷酸探针,通过原位杂交技术检测了19例福尔马林固定的前列腺癌根治术标本中的EGFR。所有切片均使用25倍物镜进行光学显微镜检查。每个视野给出三个值:1) Gleason分级(1-5级),2)核分级[小(<5.0微米)、中等(5-10微米)、大(>10微米)],以及3)EGFR染色强度评分(0,无;1,弱;2+,中度至强)。共研究了851个25倍视野的前列腺癌。所有癌症均显示至少一定程度的细胞质EGFR信息。EGFR强度评分与肿瘤核大小相关性最佳。未观察到与Gleason分级的相关性。在良性腺体的基底细胞层、高级别前列腺上皮内瘤变、基质结节、移行上皮、尿道周围腺体和神经节细胞中也发现了细胞质染色。使用未标记的EGFR探针进行的竞争性杂交实验显示杂交信号明显减弱,而用生物素标记的EGFR正义探针进行原位杂交则为阴性。用两种抗EGFR单克隆抗体对13例肿瘤进行免疫组织化学检测,仅1/13和10/13的肿瘤显示染色。EGFR表达似乎在高核分级肿瘤中最为突出。有必要进一步研究将这种生长因子作为该肿瘤的预后变量。