Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Mod Pathol. 2011 Nov;24(11):1488-99. doi: 10.1038/modpathol.2011.106. Epub 2011 Jun 24.
Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, cystadenomas, and borderline tumors. The current study was designed to gain insight into the origins of low-grade serous carcinomas (tubal versus ovarian) by comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic (using antibodies to PAX8, tubulin, calretinin, and Ki67) attributes of its putative precursor lesions, the normal tubal epithelium, and the overt malignancy. A total of 226 adnexal tissues from 178 patients were studied, including 98 adnexae removed for non-neoplastic indications, 48 serous cystadenomas, 42 serous borderline tumors, and 38 low-grade serous carcinomas. Normal distal tubal epithelium comprised an admixture of PAX8+/tubulin- secretory cells and PAX8-/tubulin+ ciliated cells with a proliferative index of ∼3%. The vast majority of ovarian surface epithelia displayed a mesothelial phenotype (calretinin+/PAX8-/tubulin-) and low proliferative index (0% (12 per 1000)), although 4% of cases also displayed foci with tubal phenotype (calretinin-/PAX8+/tubulin+). In contrast, most (78%) of the ovarian epithelial inclusions displayed a tubal phenotype and had a significantly higher proliferative index (1%) than ovarian surface epithelium, indicating that in most cases, the ovarian surface epithelium and ovarian epithelial inclusions are of different lineages. There was a progressive decrease in the population of ciliated cells, as evidenced by increasing secretory/ciliated cell ratio, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, indicating that the latter is a clonal expansion of secretory cells. Overall, the findings make a strong argument that the ovarian epithelial inclusions with a tubal phenotype is likely derived from fallopian tube through an intraovarian endosalpingiosis rather than through Mullerian metaplasia from ovarian surface epithelium. Genetic and molecular studies are needed to further confirm this finding as tubal origination of ovarian serous cancers will have a significant impact on ovarian cancer prevention and management.
卵巢低级别浆液性癌被认为是从卵巢上皮内包涵体、囊腺瘤和交界性肿瘤逐步发展而来。本研究旨在通过比较分析其潜在前驱病变（正常输卵管上皮和明显恶性肿瘤）的形态学（分泌细胞和纤毛细胞分布）和免疫表型（使用 PAX8、微管蛋白、钙视网膜蛋白和 Ki67 抗体）特征，深入了解低级别浆液性癌（输卵管起源与卵巢起源）的起源。共研究了 178 例患者的 226 例附件组织，包括 98 例因非肿瘤性原因切除的附件、48 例浆液性囊腺瘤、42 例浆液性交界性肿瘤和 38 例低级别浆液性癌。正常输卵管远段上皮由 PAX8+/微管蛋白-分泌细胞和 PAX8-/微管蛋白+纤毛细胞混合组成，增殖指数约为 3%。绝大多数卵巢表面上皮显示间皮表型（钙视网膜蛋白+/PAX8-/微管蛋白-）和低增殖指数（0%（每 1000 个中有 12 个）），尽管 4%的病例也显示有输卵管表型的灶（钙视网膜蛋白-/PAX8+/微管蛋白+）。相比之下，大多数（78%）卵巢上皮包涵体显示出输卵管表型，且增殖指数（1%）明显高于卵巢表面上皮，表明在大多数情况下，卵巢表面上皮和卵巢上皮包涵体来自不同的谱系。随着分泌细胞/纤毛细胞比值的增加，从卵巢上皮包涵体/囊腺瘤到交界性肿瘤到低级别浆液性癌，纤毛细胞的数量逐渐减少，这表明后者是分泌细胞的克隆性扩张。总的来说，这些发现有力地证明了具有输卵管表型的卵巢上皮包涵体可能是通过卵巢内的内胚层化生从输卵管而来，而不是通过卵巢表面上皮的苗勒氏上皮化生而来。需要进行遗传和分子研究来进一步证实这一发现，因为输卵管起源的卵巢浆液性癌将对卵巢癌的预防和管理产生重大影响。
