Clear Cell Carcinoma Of The Ovary: An Experience From A Regional Cancer Centre In Odisha.

Background: Clear cell carcinoma of the ovary (CCCO) shows unique clinical features. There is a remarkable difference in incidence among different ethnic populations. The reasons for these differences in incidence around the world are not known. Aim and objectives: To evaluate the clinical characteristics of patients with CCCO and to determine the impact of the stage of the disease and the extent of surgery on the prognosis of those patients. Materials and methods: A retrospective analysis of the cases of clear cell carcinoma of the ovary that were operated in the regional cancer centre, Cuttack, from January 2009 to December 2018, was performed to evaluate the clinical characteristics and prognostic factors of the patients. Results: During this study period, the incidence of CCCO was found to be 1.92%. The most common age group was 40–50 years (mean age of 44.7 years). The most common modes of presentation were abdominal distention and pain in the abdomen. Most of the cases in this study belonged to stage III C (65%), making it the most common stage in this group. 20% of the patients within the study group were nulliparous and 35% were menopausal in status.40% of the tumours were >15 cm in size. Almost 28% were lymph node positive. None in stage I had positive lymph nodes. All the cases in stage III were positive for lymph nodes. So, in stage III, 38.5% were positive for lymph nodes. 17/20 had some form of chemotherapy, of which 45% had NACT. Survival curves differ significantly between the early and advanced stages of the disease. A trend of survival benefit is seen with complete cytoreduction. Conclusion: There is a need for data regarding the incidence and specific clinicopathologic behaviour of clear cell carcinoma of the ovary in the Indian population. This is an attempt to compile the data from a single tertiary institute in eastern India over the past 10 years. This is a rare tumour and the chances of missing data are well accepted. The survival advantage of early-stage-diagnosed patients over late-stage patients is tremendous and hard to ignore. Combining the fact that clear cell carcinomas are associated with precancerous lesions like atypical endometriosis and atypical adenofibroma, there may be scope for screening. The mutational changes leading to malignancy in these precancerous lesions also need to be refined. As stated, complete cytoreduction is the key to survival advantage and the need for referral to a centre with proper expertise for the same needs to be emphasized.

SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade

Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients.