Hongo-Kohama Masako, Kurata Atsushi, Hashimoto Hirotsugu, Fujita Koji, Horiuchi Hajime, Nagao Toshitaka, Kuroda Masahiko
Departments of Molecular Pathology (M.H.-K., A.K., K.F., M.K.) Anatomic Pathology (T.N.), Tokyo Medical University Department of Diagnostic Pathology, NTT Medical Center Tokyo (H. Hashimoto, H. Horiuchi), Tokyo, Japan.
Int J Gynecol Pathol. 2017 Nov;36(6):582-592. doi: 10.1097/PGP.0000000000000373.
Although immature teratoma of the ovary is a rare disease, its pathologic grading, especially between low-grade (grade 1) and high-grade (grade 2 or 3) immature teratomas, is important for optimal therapy and prognosis. This grading, however, is currently solely dependent on quantitation of neuroepithelial components as judged by subjective assessments. As we have recently successfully studied the maturation of vascular smooth muscle cells (SMCs) in other organs using an h-caldesmon to α-smooth muscle actin (α-SMA) ratio, we decided to use this ratio to investigate a potential link between teratoma grade and SMC maturation, in combination with Ki-67 index. Sixteen immature teratomas along with 5 mature teratomas of the ovary were studied and stained with antibodies to CD31, α-SMA, h-caldesmon, and Ki-67. The number of vascular SMCs calculated using the α-SMA/CD31 ratio did not differ between teratoma grades (except between grade 0 and 3), whereas the number of mature vascular SMCs calculated using the h-caldesmon/CD31 ratio and maturation state calculated using the h-caldesmon/α-SMA ratio reduced significantly as teratoma grade progressed from 0 to 3. Furthermore, these parameters were significantly lower in high-grade than in low-grade immature teratomas (P<0.05). Ki-67 labeling index, regardless of germ cell layer, also significantly increased with teratoma grade (P<0.05). These results suggest that not only the number of neuroepithelial elements but also vascular immaturity and proliferating cell counts are biomarkers for ovarian teratoma grading. Thus, assessment of the maturity of vascular SMCs may serve as a valuable diagnostic tool for assessing teratoma maturity.
尽管卵巢未成熟畸胎瘤是一种罕见疾病，但其病理分级，尤其是低级别（1级）和高级别（2级或3级）未成熟畸胎瘤之间的分级，对于优化治疗和判断预后非常重要。然而，目前这种分级完全依赖于通过主观评估来判断神经上皮成分的定量。由于我们最近成功地利用h-钙调蛋白与α-平滑肌肌动蛋白（α-SMA）的比率研究了其他器官中血管平滑肌细胞（SMC）的成熟情况，我们决定结合Ki-67指数，利用这个比率来研究畸胎瘤分级与SMC成熟之间的潜在联系。我们研究了16例卵巢未成熟畸胎瘤以及5例卵巢成熟畸胎瘤，并用抗CD31、α-SMA、h-钙调蛋白和Ki-67的抗体进行染色。使用α-SMA/CD31比率计算的血管SMC数量在不同畸胎瘤分级之间没有差异（0级和3级之间除外），而使用h-钙调蛋白/CD31比率计算的成熟血管SMC数量以及使用h-钙调蛋白/α-SMA比率计算的成熟状态随着畸胎瘤分级从0级进展到3级而显著降低。此外，这些参数在高级别未成熟畸胎瘤中显著低于低级别未成熟畸胎瘤（P<0.05）。无论生殖细胞层如何，Ki-67标记指数也随着畸胎瘤分级显著增加（P<0.05）。这些结果表明，不仅神经上皮成分的数量，而且血管不成熟和增殖细胞计数都是卵巢畸胎瘤分级的生物标志物。因此，评估血管SMC的成熟度可能是评估畸胎瘤成熟度的一种有价值的诊断工具。
