Herbst H, Sauter M, Mueller-Lantzsch N
Institut für Pathologie, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Am J Pathol. 1996 Nov;149(5):1727-35.
Antibodies against proteins encoded by human endogenous retrovirus (HERV)-K family genes are consistently found in the sera of patients with classical seminoma. Furthermore, HERV-K Gag-encoded protein could be detected in corresponding tumor biopsies. Addressing questions as to the extent of HERV gene expression in biologically related lesions, we studied various testicular and ovarian germ cell tumors (GCTs), GCT precursor lesions, and gestational trophoblastic disease (GTD) for the presence of HERV-K gene transcripts in tissue sections. By in situ hybridization using four non-overlapping, isotopically labeled RNA probes specific for HERV-K gag and env sequences on archival tissue samples, consistent HERV-K expression of gag and env genes was found to be common to all GCTs and their testicular precursor lesions with the exception of teratomas, mature and immature, and spermatocytic seminomas. HERV-K expression was also found in malignant GTD (choriocarcinoma) but not in benign GTD (noninvasive molar pregnancy). There was no evidence for HERV-K expression in differentiated embryonal and adult tissues as well as a total of 53 tumors other than GCT or GTD. The findings point to a common molecular pathoetiology of GCT and malignant GTD, have implications for the classification of GCTs, and support the concept of carcinoma in situ as a precursor lesion common to all forms of testicular GCT.
在经典型精原细胞瘤患者的血清中，始终能检测到针对人类内源性逆转录病毒（HERV）-K家族基因编码蛋白的抗体。此外，在相应的肿瘤活检组织中可检测到HERV-K Gag编码蛋白。为了探究HERV基因在生物学相关病变中的表达程度，我们研究了各种睾丸和卵巢生殖细胞肿瘤（GCT）、GCT前驱病变以及妊娠滋养细胞疾病（GTD）的组织切片中HERV-K基因转录本的存在情况。通过对存档组织样本使用四种针对HERV-K gag和env序列的非重叠、同位素标记的RNA探针进行原位杂交，发现除成熟和未成熟畸胎瘤以及精母细胞性精原细胞瘤外，所有GCT及其睾丸前驱病变中gag和env基因均普遍存在一致的HERV-K表达。HERV-K表达也见于恶性GTD（绒毛膜癌），但不见于良性GTD（非侵袭性葡萄胎妊娠）。在分化的胚胎组织和成人组织以及除GCT或GTD外的总共53种肿瘤中，均未发现HERV-K表达的证据。这些发现表明GCT和恶性GTD具有共同的分子病理病因，对GCT的分类具有重要意义，并支持原位癌作为所有形式睾丸GCT共同前驱病变的概念。
