Expression of ARID1A in ovarian seromucinous neoplasms and its clinicopathological significance

Abstract

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 p53staining 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 20seromucinous borderline tumors, and 2 of the 11seromucinous carcinomas. According to FIGO 2014staging system, there were 4 cases of ⅠA, 3 cases of ⅡA and 4 cases of ⅢC. 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 stage ⅢC 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 type Ⅰ tumor of dualistic model of epithelial ovarian cancer, with favourable prognosis.