Cierna Z, Mego M, Jurisica I, Machalekova K, Chovanec M, Miskovska V, Svetlovska D, Kalavska K, Rejlekova K, Kajo K, Mardiak J, Babal P
Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
BMC Cancer. 2016 Aug 4;16:597. doi: 10.1186/s12885-016-2644-z.
Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Fibrillins, which are integral components of microfibrils are suggested to be involved in cancer pathogenesis and maintenance of embryonic stem cells pluripotency. The aim of this study was to examine fibrillin-1 (FBN-1) expression in TGCTs patients.
Surgical specimens from 203 patients with TGCTs were included into the translational study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in adjacent non-neoplastic testicular tissue in all available cases. Tissue samples were processed by the tissue microarray method. FBN-1 was detected by immunohistochemistry using goat polyclonal antibody and the expression was evaluated by the multiplicative quickscore (QS).
The highest FBN-1 positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1 (QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of TGCTs was significantly lower in comparison to expression in GCNIS (all p <0.001). Seminoma had significantly higher expression compared to EC, ChC and TER (all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity, positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS were 97.1, 98.8, 98.6 and 97.7 %.
FBN-1 is overexpressed in TGCTs and especially in GCNIS when compared to non-neoplastic testicular tissue in patients with germ cell tumors and could be involved in germ cell neoplasia in situ development.
原位生殖细胞肿瘤(GCNIS)是睾丸生殖细胞肿瘤(TGCTs)的侵袭前阶段。原纤维蛋白是微原纤维的重要组成部分,被认为参与癌症发病机制和维持胚胎干细胞多能性。本研究的目的是检测TGCTs患者中纤连蛋白-1(FBN-1)的表达。
203例TGCTs患者的手术标本纳入本转化研究。在所有可用病例中,评估肿瘤组织、GCNIS和相邻非肿瘤性睾丸组织中的FBN-1表达。组织样本采用组织芯片方法处理。使用山羊多克隆抗体通过免疫组织化学检测FBN-1,并通过乘法快速评分(QS)评估表达。
在GCNIS中检测到最高的FBN-1阳性(平均QS = 11.30),大多数病例(77.1%)中FBN-1过表达(QS>9)。与GCNIS中的表达相比,TGCTs所有亚型中FBN-1的表达均显著降低(所有p<0.001)。精原细胞瘤的表达与胚胎癌(EC)、绒毛膜癌(ChC)和卵黄囊瘤(TER)相比显著更高(所有p<0.05),但与卵黄囊瘤(YST)相比无显著差异(p = 0.84)。在非肿瘤性睾丸组织中,FBN-1阳性率非常低(平均QS = 0.02)。FBN-1表达对GCNIS诊断的敏感性、特异性、阳性和阴性预测值分别为97.1%、98.8%、98.6%和97.7%。
与生殖细胞肿瘤患者的非肿瘤性睾丸组织相比,FBN-1在TGCTs中尤其是在GCNIS中过表达,可能参与原位生殖细胞肿瘤的发生发展。