Kalfa N, Philibert P, Patte C, Thibaud E, Pienkowski C, Ecochard A, Boizet-Bonhoure B, Fellous M, Sultan C
Service d'hormonologie, hôpital Lapeyronie, CHU de Montpellier, Montpellier, France.
Gynecol Obstet Fertil. 2009 Jan;37(1):33-44. doi: 10.1016/j.gyobfe.2008.06.026. Epub 2008 Dec 31.
Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnosis of a tumor, revealed by clinical signs of hyperoestrogeny, is an important prognostic factor. The pathophysiology of these tumors is still debatable and several cellular- and molecular-abnormal signals could be implicated in their development. The role of growth factors and oncogenes through the signaling pathway of MAP kinase is still discussed. According to our data, FSH signaling-transduction pathway, such as a constitutionally activated Galphas, could also be implicated in the induction of granulosa cell proliferation and seems to modulate the invasiveness of the tumor. Last, we have described a low-expression pattern or an extinction of an ovarian-determination gene, FOXL2, which is related to a worse prognosis of this tumor.
卵巢性索间质肿瘤是起源于卵巢非生殖细胞的罕见肿瘤。二十年前，幼年型颗粒细胞瘤（GCT）作为该组中的一个特定实体被识别出来，这使得对儿童期这些肿瘤的治疗得到了改善。然而，关于该疾病自然病程的报道数据很少，并且尚未确定可靠的预后因素。在此，我们基于40例儿童病例回顾颗粒细胞瘤的临床和遗传学方面。这项全国性合作研究由法国儿童癌症协会和八个儿科内分泌临床科室参与。我们发现，由高雌激素临床体征揭示的肿瘤早期诊断是一个重要的预后因素。这些肿瘤的病理生理学仍存在争议，几种细胞和分子异常信号可能与其发生发展有关。通过丝裂原活化蛋白激酶信号通路的生长因子和癌基因的作用仍在讨论中。根据我们的数据，FSH信号转导途径，如组成性激活的Gαs，也可能参与颗粒细胞增殖的诱导，并且似乎调节肿瘤的侵袭性。最后，我们描述了一种卵巢决定基因FOXL2的低表达模式或缺失，这与该肿瘤的较差预后相关。
