睾丸弥漫性大B细胞淋巴瘤中OCT4蛋白的表达及其临床病理特征

Clinicopathologic features and expression of OCT4 protein in testicular diffuse large B cell lymphoma

目的 分析睾丸弥漫性大B细胞淋巴瘤（DLBCL）中OCT4和SALL4等的表达情况,并探讨联合应用OCT4、SALL4和CD20等免疫组织化学标志物在睾丸生殖细胞肿瘤和DLBCL诊断和鉴别诊断上的应用价值.方法 收集18例睾丸DLBCL石蜡标本,光镜下观察组织学特征,采用免疫组织化学法检测CD20、CD3、CD5、CD10、bcl-6、MUM1、Ki-67、bcl-2、c-MYC、OCT4、SALL4等蛋白的表达,并进行免疫表型的分析.结果 18例睾丸DLBCL中,肿瘤细胞弥漫强表达B细胞标志物CD20、PAX5,均不表达CD21、CD3、cyclin D1、SALL4、CD117及胎盘碱性磷酸酶（PLAP）,3例表达CD5,16例表达bcl-2,8例表达c-MYC,7例同时表达bcl-2和c-MYC（7/18）,Ki-67阳性指数40%～95%.根据Hans分类,18例睾丸DLBCL中,4例起源于生发中心B细胞（GCB）型,其余14例起源于non-GCB型.2例（〉50%以上肿瘤细胞）中等强度表达OCT4（2/18）,且同时表达CD5和bcl-2,其中单因素生存分析显示高临床分期及CD5、OCT4表达预后差（P〈0.05）.进一步多因素COX模型分析显示临床分期、CD5以及OCT4是独立预后因素.结论 少数睾丸DLBCL可以表达OCT4,应联合OCT4、SALL4和CD20等免疫组织化学标志物,避免误诊.OCT4与CD5、bcl-2等同时表达,提示表达OCT4蛋白的睾丸DLBCL的生物学行为更具有侵袭性.

Objective To evaluate the expression of OCT4 and SALL4 in testicular diffuse large B-cell lymphoma （DLBCL）, and the utility of an immunohistochemical （IHC） panel of OCT4, SALL4 and CD20 in the differential diagnosis of DLBCL and GCT of the testis.Methods Eighteen cases of testicular DLBCL were selected.IHC method was used to detect the protein expression of CD20, CD3, CD5, CD10, bcl-6, MUM1, Ki-67, bcl-2, c-MYC, OCT4 and SALL4.Results Among the 18 cases, CD20 and PAX5 were strongly and diffusely expressed in all cases, while CD21, CD3, cyclinD1, SALL4, CD117 and PLAP were all negative.CD5, bcl-2 and c-myc were expressed in 3, 16 and 8 cases, respectively.Ki-67 proliferation index ranged from 40%-95%.Bcl-2 and c-MYC were co-expressed in seven cases.Four cases were GCB-DLBCL and the remaining 14 cases were non-GCB-DLBCL,according to Hans algorithm.Nuclear OCT4 expression was present in two cases, which demonstrated moderate expression in 〉50% of neoplastic cells.Univariate analysis showed that clinical stage, CD5 and OCT4 expression were relevant to prognosis.Multivariate Cox regression analysis further confirmed that clinical stage, CD5 and OCT4 were independent prognostic factors in patients with testicular DLBCL.Conclusions Care should be exercised in using OCT4 as the sole marker of germ cell differentiation in the testis.The association of OCT4 and CD5, bcl-2 co-expression raises the question of whether OCT4 expression in DLBCL may reflect more aggressive biology.