Molecular association of functioning stroma with carcinoma cells in the ovary: A preliminary study.

The cancer stroma serves an important role in tumour behaviours, including invasion, metastasis, and response to chemotherapy. The stroma of ovarian carcinoma is sometimes specialized, with luteinisation and/or hyperthecosis, and is designated as the 'functioning stroma' because it exerts endocrine function and produces sex steroid hormones. In the present study, 14 ovarian cancers with functioning stroma, comprising 7 endometrioid carcinomas and 7 clear cell carcinomas, were analysed to evaluate the molecular association of the functioning stroma with carcinoma cells. The median age of the patients was 67 years (range, 52-85 years); 13 patients were postmenopausal, and one was in perimenopause. Serum oestrogen values ranged from 10 to 129 ng/ml, with a median of 51 ng/ml. Sequence abnormalities in AT-rich interaction domain 1A (ARID1A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), Kirsten rat sarcoma viral proto-oncogene (KRAS) and phosphatase and tensin homolog (PTEN) were examined in whole tumours. For cancers positive for sequence abnormalities, their localization in carcinoma cells and/or stromal cells was examined. A total of 8 mutations - ARID1A (L2155L), PIK3CA (H1047R), KRAS (Q12V, E31K, Q61L), and PTEN (C105fs*8) - were identified in the whole tumours of 5 patients. Seven of these eight mutations were detected only in carcinoma cells. However, one case of endometrioid carcinoma had a KRAS (E31K) mutation in both carcinoma and stromal cells. In conclusion, although functioning stromal cells of ovarian cancer are usually thought to be non-neoplastic, some may share an origin with carcinoma cells.