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Title: [Diagnostic value of immunohistochemistry and FISH for chromosome 12p in type Ⅱ testicular germ cell tumors].
Author: Shen Q, Rao Q, Yu B, Xia QY, Bao W, Lu ZF, Shi QL, Zhou XJ.
Journal: Zhonghua Nan Ke Xue; 2016 Aug; 22(8):692-697. PubMed ID: 29019224.
Abstract:
OBJECTIVE: To study the pathological morphology, immunohistochemical characteristics, and molecular changes of type Ⅱ testicular germ cell tumors (TGCT) and investigate the possible value of immunohistochemistry and fluorescence in situ hybridization (FISH) in the diagnosis of TGCT. METHODS: We collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17 cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which normal testicular tissue was found in 20 and non-TGCT in 6. We detected the expressions of different antibodies in various subtypes of TGCT by immunohistochemistry and determined the rate of chromosome 12p abnormality using FISH. RESULTS: The immunophenotypes varied with different subtypes of TGCT. SALL4 and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4 showed strongly positive expressions in invasive seminoma and germ cell neoplasia in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30). CONCLUSIONS: The majority of TGCT can be diagnosed by histological observation, but immunohistochemical staining is crucial for more accurate subtypes and valuable for selection of individualized treatment options and evaluation of prognosis. Chromosome 12p abnormality is a specific molecular alteration in type Ⅱ TGCT, which is useful for ruling out other lesions. 目的：分析Ⅱ型睾丸生殖细胞肿瘤(TGCT)的各亚型病理形态以及免疫组化特点、分子生物学改变，探讨免疫组化染色（IHC）及荧光原位杂交（FISH）检测在TGCT诊断分型中的意义。方法：收集97例TGCT（含有精原细胞瘤成分75例，胚胎癌成分17例，卵黄囊瘤成分11例，成熟性畸胎瘤16例，未成熟畸胎瘤3例，表皮囊肿1例），正常睾丸组织20例，以及非生殖细胞肿瘤的睾丸肿瘤6例。通过IHC检测TGCT各亚型对于不同抗体的阳性表达情况，并运用FISH技术检测各亚型中12号染色体短臂等臂和扩增的发生率。结果： TGCT各亚型的免疫表型各有不同，人类婆罗双树样基因-4（SALL4）及胎盘碱性磷酸酶（PLAP）最广谱、敏感性高，CD117及人八聚体结合转录因子4（OCT4）在浸润性精原细胞瘤和原位生殖细胞瘤（GCNIS）中强阳性表达，而在正常生精小管不表达。卵黄囊瘤显著表达人磷脂酰肌醇蛋白聚糖3（GPC3），表达范围和强度均优于人调节T细胞特异转录因子3（GATA3）和甲胎蛋白（AFP）。胚胎癌表达人广谱细胞角蛋白（CKpan）、OCT4、CD30。绒癌表达人绒毛膜促性腺激素（hCG）。浸润性TGCT中12号染色体短臂发生等臂和扩增的阳性率为96.7%（29/30）。结论：临床病理工作中，绝大部分病例单凭组织形态观察即可诊断TGCT，IHC检测利于更精确的分型，对于个体化治疗选择和预后评估意义重大。12号染色体短臂捕获是Ⅱ型TGCT的特异性分子改变，有助于排除其他病变。.

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