Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, The Netherlands.
Int J Gynecol Cancer. 2012 Mar;22(3):457-64. doi: 10.1097/IGC.0b013e3182434a81.
The pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.
Cases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.
Nine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).
This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.
浆液性卵巢癌（SOC）的发病机制尚不清楚。最近，子宫内膜上皮内癌（EIC）被认为是 SOC 的前体病变。本研究探讨了 EIC 作为 SOC 前体的模型。
选择 SOC 中存在无侵袭性或表浅侵袭性浆液性病变、伴/不伴非典型增生的增生性病变或子宫内膜 EIC 的病例纳入本研究。由一名妇科病理学家对双侧卵巢、输卵管和子宫的组织切片进行广泛复查。对 EIC 和 SOC 均进行 p53、Ki-67、雌激素受体和孕激素受体免疫组化染色、TP53 突变分析和原位倍性分析。
确定了 9 例 SOC 合并子宫内膜 EIC。EIC 和 SOC 中 p53、Ki-67、雌激素受体和孕激素受体的免疫组化染色显示出几乎相同的表达模式和相似的强度。在 33%的病例中，SOC 和同时存在的 EIC 中发现了相同的 TP53 突变，提示其具有克隆起源。DNA 倍性分析作为肿瘤进展的标志物，显示 SOC 中存在更多的非整倍体核，与相应的 EIC 相比（P=0.039）。此外，SOC 中每个细胞核的平均 DNA 量更高（即更多的非整倍体），与 EIC 相比（P=0.039）。
本研究首次提示 EIC 可能是 SOC 的前体病变。这一发现可能对未来卵巢癌的管理产生重大的临床影响，并强调了 EIC 作为早期 SOC 检测和预防的可能靶点。
