Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r2=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
目的： 探讨CXorf67、H3K27me3在中枢神经系统生殖细胞肿瘤（GCT）中的表达情况及其在诊断和鉴别诊断中的价值。 方法： 选取复旦大学附属华山医院病理科中枢神经系统GCT病例370例，通过免疫组织化学（EnVision法）检测石蜡标本中CXorf67、H3K27me3及常用指标OCT4、胎盘碱性磷酸酶（PLAP）、CD117、D2-40、CD30在中枢神经系统GCT不同亚型的表达情况，采用列联表及受试者工作特征曲线（ROC曲线）下面积比较各指标灵敏度及特异度。 结果： （1）男性282例，女性88例，年龄范围2~57岁，平均发病年龄19岁，中位年龄17岁；在具有生殖细胞瘤成分的GCT中，男性及鞍区发病患者比例更高（P<0.05）。（2）CXorf67特异性表达于原始生殖细胞及生殖细胞瘤细胞核上，在其他非生殖细胞瘤性GCT中不表达；H3K27me3在生殖细胞瘤中缺失表达，在其他亚型瘤细胞及周围正常组织细胞核上阳性表达。（3）在283例具有生殖细胞瘤成分的GCT中，H3K27me3均缺失表达，CXorf67阳性表达率为90.5%（256/283）；二者具有显著负相关性（r2=-0.831，P<0.01）；PLAP、OCT4、CD117、D2-40表达率依次为：81.2%（231/283）、89.4%（253/283）、73.9%（209/283）、88.3%（250/283）。（4）在63例含生殖细胞瘤的混合性GCT中，H3K27me3均缺失表达，CXorf67阳性率为84.1%（53/63），PLAP、OCT4、CD117、D2-40表达率依次为：79.4%（50/63）、79.4%（50/63）、66.7%（42/63）、87.3%（55/63）。（5）各指标ROC曲线下面积排名依次为H3K27me3、CXorf67、D2-40、OCT4、PLAP、CD117（P<0.05）。 结论： CXorf67和H3K27me3两指标灵敏度高、特异性强，呈显著负相关，可以作为新的特异性免疫组织化学指标联合应用于GCT的诊断及鉴别诊断。.