去分化和未分化卵巢癌(DDOC/UDOC)是罕见的肿瘤,由存在未分化癌定义。在这项研究中,我们详细介绍了临床,病态,一系列DDOC/UDOC的免疫组织化学和分子特征。我们收集了23个DDOC/UDOC的多机构队列,并对核心SWItch/蔗糖不可发酵(SWI/SNF)复合蛋白(ARID1A,ARID1B,SMARCA4和SMARCB1),错配修复(MMR)蛋白和p53。对一组病例进行了基于阵列的全基因组DNA甲基化和拷贝数变异(CNV)分析,并与先前报道的未分化子宫内膜癌(UDEC)队列进行了比较。卵巢小细胞癌,高血钙型(SCCOHT),和卵巢高级别浆液性癌(HGSC)。23例DDOC/UDOC患者的年龄范围为22至71岁(平均50岁),大多数患者患有卵巢外疾病(16/23)。对19例患者进行了临床随访。除了两个病人,其余17名患者全部死于疾病,在II-IV期患者中,疾病进展迅速,导致一年内死亡(中位疾病特异性生存期为3个月)。22例具有可解释的免疫组织化学结果的病例中,有18例显示核心SWI/SNF蛋白的表达缺失,预期会导致SWI/SNF复合物失活,10例显示ARID1A和ARID1B的共同缺失,7损失SMARCA4和1损失SMARCB1。23例中有6例为MMR缺陷。20例中有2例表现出突变型p53免疫反应性。甲基化谱显示DDOC/UDOC与UDEC的共聚集,其共同不同于SCCOHT和HGSC。DDOC/UDOC显示中等程度的CNV,与SCCOHT相比略大,但与HGSC相比要少得多。总的来说,DDOC/UDOC,像它的子宫内膜对应物一样,是一种高度侵袭性的,其特征是核心SWI/SNF复合蛋白频繁失活和MMR缺陷。其分子谱与UDEC重叠,同时与SCCOHT和HGSC不同。
Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A,
ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and
ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.