Are polyploid giant cancer cells in high grade serous carcinoma of the ovary blastomere-like cancer stem cells?

Abstract

Polyploid giant cancer cells, either multinucleated or mononucleated, in high grade serous carcinoma of the ovary have been previously recognized. Different theories including degenerative changes or an important step in the development of high grade serous carcinoma have been proposed. Here we investigate possible explanations for the presence of polyploid giant cancer cells in high grade serous carcinoma. We reviewed 33 cases of ovarian high grade serous carcinoma (12 stage I, 7 stage II, and 14 stage III). We counted the number of polyploid giant cancer cells in 20 consecutive 10× fields. In 11 cases where polyploid giant cancer cells were easily found, immunohistochemistry for Ki67, p53, and OCT 3/4 was performed. Patients with polyploid giant cancer cells were older than those without. Polyploid giant cancer cells were more frequent in stage I lesions (75%) than in stages II or III (57% in both) and less frequent in metastases compared with primary ovarian tumors. Mitotic figures were present in regular sized cells but were absent in polyploid giant cancer cells. OCT3/4 was negative in all cases assessed. In 8 cases, more than 70% of the mononuclear cells were positive for Ki-67, similar to the percentage of Ki-67 positive cells in polyploid giant cancer cells. p53 had a perfect correlation in regular sized cancer cells and in polyploid giant cancer cells.Polyploid giant cancer cells are neither degenerative cells nor traditional cancer stem cells but most probably represent an intermediate step between stem cells and mature tumor cells formed by endoreplication.