Gopalan Anuradha, Dhall Deepti, Olgac Semra, Fine Samson W, Korkola James E, Houldsworth Jane, Chaganti Raju S, Bosl George J, Reuter Victor E, Tickoo Satish K
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mod Pathol. 2009 Aug;22(8):1066-74. doi: 10.1038/modpathol.2009.66. Epub 2009 Apr 24.
Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered 'embryonal carcinoma-like high-grade'. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1+, 1-25%; 2+, 26-50%; and 3+, >50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 -3+, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 -3+, all embryonal carcinomas and -2 to 3+, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 -2 to 3+, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2+, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3+ for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only 'embryonal carcinoma-like high-grade' nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. 'Embryonal carcinoma-like high-grade' nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.
干细胞标志物OCT3/4，以及最近发现的SOX2和生长分化因子3（GDF3），据报道在生殖细胞肿瘤中表达情况各异。我们研究了这些标志物在不同睾丸生殖细胞肿瘤中的免疫组化表达情况，以及它们在鉴别诊断这些肿瘤中形态学上难以分类的成分方面的效用。共研究了50例混合性睾丸生殖细胞肿瘤，其中43例还包含难以分类的区域。在这些区域，记录了多个形态学参数，与典型胚胎癌相似的高级别核细节被视为“胚胎癌样高级别”。对OCT3/4、c-kit、CD30、SOX2和GDF3进行免疫组化染色，并对每个成分按0级（阴性）、1+级（1 - 25%阳性染色细胞）、2+级（26 - 50%阳性染色细胞）和3+级（>50%阳性染色细胞）进行分级。这些肿瘤中鉴定出的不同成分包括精原细胞瘤（8例）、胚胎癌（50例）、卵黄囊瘤（40例）、畸胎瘤（40例）、绒毛膜癌（3例）和未分类的管内生殖细胞肿瘤（35例）。通过免疫组化，染色模式为：OCT3/4 - 3+，所有精原细胞瘤、胚胎癌和管内生殖细胞肿瘤；SOX2 - 3+，所有胚胎癌，以及 - 2至3+，11/14（79%）未成熟畸胎瘤中的原始神经外胚层成分；GDF3 - 2至3+，所有卵黄囊瘤、精原细胞瘤和管内生殖细胞肿瘤，以及1至2+，40/50胚胎癌。43例中有34例（79%）难以分类的区域OCT3/4、CD30和SOX2染色为3+，与胚胎癌相似。在这些区域中，只有“胚胎癌样高级别”核细节与这种免疫表型显著相关。因此，SOX2在胚胎癌和畸胎瘤的原始神经外胚层中表达，与OCT3/4不同，在管内生殖细胞肿瘤和精原细胞瘤中不表达。因此，它可能有助于区分精原细胞瘤和胚胎癌，并可能有助于诊断精原细胞瘤中的早期癌性分化。在没有OCT3/4和CD30的情况下，GDF3阳性结合形态学特征有助于卵黄囊瘤的诊断。“胚胎癌样高级别”核细节是在难以分类的区域诊断胚胎癌的最重要形态学标准。
