Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Office of the Chief Medical Examiner, Farmington, CT, USA.
Mod Pathol. 2017 Oct;30(10):1467-1475. doi: 10.1038/modpathol.2017.66. Epub 2017 Jun 30.
Although homozygosity is well documented in mature teratomas, the genetic zygosity of ovarian immature teratomas and mixed germ cell tumors is less well studied. Ten cases of mature cystic teratomas, eleven cases of grade 2 or 3 immature teratomas, and seven cases of mixed germ cell tumors with an immature teratoma component were investigated by short tandem repeat genotyping to interrogate their genetic zygosity. DNA genotyping was informative in eight mature teratomas, seven immature teratomas and six cases of mixed germ cell tumors. Out of the eight mature teratomas, five cases showed partial or complete homozygosity (63%) with two cases demonstrating complete homozygosity (25%). Of the immature teratomas, six cases showed partial or complete homozygosity (86%) with two cases demonstrating complete homozygosity (29%). For the mixed germ cell tumors, two cases showed partial homozygosity (33%) and none displayed complete homozygosity. Long-term clinical follow-up was available for five immature teratomas (mean follow-up 110 months) and five mixed germ cell tumors (mean follow-up 66 months). None of the five patients with pure immature teratoma had a recurrence; in contrast, four out of five mixed ovarian germ cell tumors recurred between 4 months to 8 years (P=0.048). In conclusion, both immature and mature teratomas harbor frequent genetic homozygosity suggesting a common cellular origin involving germ cells at the same developmental stage. The difference in the rate of homozygosity and tumor recurrence between pure immature teratomas and mixed germ cell tumors suggests that the two entities may involve different pathogenetic pathways and likely pursue different biological behaviors.
尽管在成熟的畸胎瘤中已经有充分的同型合子报道，但卵巢未成熟畸胎瘤和混合生殖细胞肿瘤的遗传同型合子情况研究较少。本研究通过短串联重复序列基因分型分析了 10 例成熟囊性畸胎瘤、11 例 2 级或 3 级未成熟畸胎瘤和 7 例含有未成熟畸胎瘤成分的混合生殖细胞肿瘤，以研究其遗传同型合子情况。在 8 例成熟畸胎瘤、7 例未成熟畸胎瘤和 6 例混合生殖细胞肿瘤中，DNA 基因分型是有意义的。在 8 例成熟畸胎瘤中，5 例（63%）显示部分或完全同型合子，其中 2 例（25%）显示完全同型合子。在未成熟畸胎瘤中，6 例（86%）显示部分或完全同型合子，其中 2 例（29%）显示完全同型合子。对于混合生殖细胞肿瘤，2 例（33%）显示部分同型合子，无完全同型合子。5 例未成熟畸胎瘤（平均随访 110 个月）和 5 例混合生殖细胞肿瘤（平均随访 66 个月）有长期临床随访。5 例纯未成熟畸胎瘤患者无一例复发；相比之下，5 例混合卵巢生殖细胞肿瘤中有 4 例在 4 个月至 8 年内复发（P=0.048）。总之，未成熟和成熟畸胎瘤都存在频繁的遗传同型合子，提示涉及同一发育阶段的生殖细胞的共同细胞起源。纯未成熟畸胎瘤和混合生殖细胞肿瘤之间同型合子和肿瘤复发率的差异表明，这两种实体可能涉及不同的发病途径，可能具有不同的生物学行为。
