卵巢浆黏性肿瘤ARID1A的表达及其临床病理意义

Expression of ARID1A in ovarian seromucinous neoplasms and its clinicopathological significance

目的探讨卵巢浆黏性肿瘤的临床病理特征及免疫组织化学特点。方法收集解放军总医院第一医学中心病理科2006年6月至2018年12月确诊的卵巢浆黏性肿瘤的临床病理资料,分析其组织病理学特点,并通过免疫组织化学EnVision法检测细胞角蛋白(CK)7、PAX8、雌激素受体(ER)、孕激素受体(PR)、WT1、p16、p53以及ARID1A编码蛋白Baf250a的表达。结果本组卵巢浆黏性肿瘤共75例,其中良性浆黏性囊腺瘤30例,年龄12~83岁,平均年龄36岁,镜下由宫颈内膜型黏液上皮和浆液性上皮混合组成,每种成分占10%以上。交界性浆黏性肿瘤34例,患者年龄21~72岁,平均年龄39岁,7例伴发子宫内膜异位症;镜下见宽大的乳头状结构,分支复杂,衬覆上皮层次增加,细胞成分复杂,主要为宫颈内膜样黏液细胞(非肠型,无杯状细胞),其次为嗜酸性细胞,其他可见透明细胞、鞋钉样细胞、纤毛细胞、子宫内膜样细胞等。间质疏松水肿,常伴大量急性炎性细胞浸润。浆黏性癌11例,患者年龄26~61岁,平均年龄40岁,2例伴发子宫内膜异位症;镜下呈乳头状、融合腺样、微腺或实性结构,多呈扩张性浸润生长方式,局部呈破坏性浸润;细胞成分复杂,与交界性肿瘤相似。免疫组织化学显示ARID1A编码蛋白Baf250a阳性表达于肿瘤细胞核,交界性浆黏性肿瘤表达缺失率30%(6/20;其中1例完全缺失,5例部分缺失),浆黏性癌表达缺失比例2/11(均为部分缺失);CK7、PAX8、p16在肿瘤细胞表达阳性;ER、PR均为阳性(10%~80%),WT1阴性,p53野生型表达,Ki-67阳性指数20%~60%。浆黏性癌10例行全子宫、双侧/单侧附件、大网膜、阑尾切除术及淋巴结清扫术,1例行患侧附件及阑尾切除术,术后均行化疗。根据2014版卵巢癌国际妇产科联盟(FIGO)分期,ⅠA期4例,ⅡA期3例,ⅢC期4例。浆黏性癌8例存活(其中2例复发),1例死于疾病,2例失访。交界性肿瘤34例均行患侧附件切除术,均存活,1例复发。结论浆黏性肿瘤具有较为独特的临床病理学特征,交界性浆黏性肿瘤与浆黏性癌均具有复杂的结构和细胞成分。ARID1A作为肿瘤抑制基因,在致瘤转化过程中起一定作用,在浆黏性肿瘤中具有表达缺失的特点,以及p53野生型表达,均支持浆黏液性肿瘤是Ⅰ型肿瘤而非Ⅱ型肿瘤,患者预后相对较好。

Objective To investigate the clinical,pathological and immunohistochemical features of seromucinous neoplasms,including seromucinous cystadenoma,borderline tumour and seromucinous carcinomas of the ovary.Methods A retrospective review of the seromucinous neoplasms collected between June 2006 and December 2018 was conducted at the First Medical Center of PLA General Hospital.EnVision immunohistochemical staining was used to detect the expression of CK7,PAX8,ER,PR,WT1,p16,p53 and Baf250a which was encoded by the ARID1A gene.Results A total of 75 ovarian seromucinous neoplasms were included.There were 30 cases of benign seromucinous cystadenoma,whose patients aged 12 to 83 years(mean,36 years).The tumor histologically composed of endocervical-type mucinous epithelium and serous-type cells,each of which accounted for more than 10%.Among the 34 cases of seromucinous borderline tumour including 7 cases with concurrent endometriosis,the patients aged 21 to 72 years(mean,39 years).Characteristic histologic features were broad papilla structure and an admixture of cell types,predominant endocervical-like mucinous cells(non-intestinal,no goblet cells),eosinophilic cells and others such as clear cells,hobnail cells,ciliated cells,and endometrioid cells.The larger papillae tended to have oedematous stroma containing neutrophils.In the 11 cases of seromucinous carcinomas including 2 cases with concurrent endometriosis,patients aged 26 to 61 years(mean,40 years).Seromucinous carcinomas exhibited a predominant papillary architecture with smaller components of confluent glandular,microglandular and solid structure,expansive stromal invasion pattern,and sometimes locally destructive infiltration.An admixture of epithelial cell types was in seromucinous carcinomas,as well as borderline tumour.Immunohistochemically,the tumours were positive for CK7,PAX8,p16,estrogen receptor and progesterone receptor(positive in 10%to 80%of the cases).They were negative for WT1,while p53 staining showed a"wild-type"pattern.The Ki-67 positive rate was 20%to 60%.Loss of ARID1A-encoded protein Baf250a staining was observed in 6(30%)of the 20 seromucinous borderline tumors,and 2 of the 11 seromucinous carcinomas.According to FIGO 2014 staging system,there were 4 cases ofⅠA,3 cases ofⅡA and 4 cases ofⅢC.Follow-up information was available in 9 patients of seromucinous carcinomas,and 2 lost to follow-up.Eight were alive(follow-up for 6 to 108 months),including 2 patients with relapse,but 1 patient who initially presented with a stageⅢC tumor died of disease 60 months after the cancer diagnosis.Thirty-four patients of borderline tumour were all alive at the end of follow-up,including 1 with relapse.Conclusions Seromucinous neoplasms have characteristic histopathological and immunopathological features.Both borderline tumors and carcinomas have complex structures and cellular components.ARID1A as a tumor-suppressor gene plays a role in the oncogenesis of ovarian seromucinous neoplasms.The loss of staining with ARID1A-encoded Baf250a and wild-type p53 in seromucinous neoplasms together support that seromucinous neoplasms could be typeⅠtumor of dualistic model of epithelial ovarian cancer,with favourable prognosis.