In vitro chemosensitivity in ovarian carcinoma: Comparison of three leading assays

Abstract

Material and Methods:Fresh tumoral tissue samples of 26 newly diagnosed primary ovarian cancer patients were studied with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) and differential staining cytotoxicity (DISC) assays. Chemosensitivity of tumors were studied for paclitaxel, carboplatin, docetaxel, topotecan, gemcitabine, and doxorubicin with each of the three assays. Subgroup analysis was performed for stage, grade, and histologic type. Results:The in vitro chemosensitivity results of MTT, ATP, and DISC assays were found to be similar. The subgroups in which in vitro assays would be more useful were encountered for patients with advanced stage and serous histology ovarian carcinoma. Conclusions:In vitro chemosensitivity can be determined in ovarian carcinoma with ATP, MTT, or DISC assays before the initiation of chemotherapy. These three assays correlate well with each other and are particularly useful for serous and advanced cancers. Large prospective studies comparing standard versus assay-directed therapy with an endpoint of overall survival are required before routine clinical utilization of these assays. (J Turk Ger Gynecol Assoc 2016; 17: 35-40) Keywords: Ovarian cancer, in vitro chemosensitivity, ATP, MTT, DISC Received: 20 January, 2016 Accepted: 22 January, 2016 In vitro chemosensitivity in ovarian carcinoma:Comparison of three leading assays Black and Speer in 1950s (9). The chemosensitivity tests allow detecting the cytotoxic, cytostatic, and apoptotic effects of the chemotherapeutic agent outside the organism. Such an approach is particularly thought to prevent the harmful toxic effects of these agents. Many molecular and cellular assays have been developed to date for the in vitro detection of chemosensitivity. The molecular methods detect the chemosensitivity at the protein or gene level (10,11). Although a single gene may be sufficient for the evaluation, a cytotoxic drug sometimes generates an excessive cellular response (12, 13). Cellular methods provide the efficacy results for multiple drugs simultaneously. Several tests based on cellular methods, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyum bromide (MTT) chemosensitivity assay, adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA), and differential staining cytotoxicity (DISC) assays, have been described in the literature. Despite the logic that any method that predicts the chemosensitivity of a tumor for an individual patient would be helpful for better regimens, no chemosensitivity assay has achieved widespread clinical use to date. In a study from USA with 262 patients, all the patients were treated empirically, but a chemosensitivity assay was also performed concomitantly for all. In addition, in the subgroup of patients treated with assay-sensitive agents, progression-free survival (PFS) and OS are found to be improved, and further analysis has confirmed these results (14,15). Recently, an observational study h...

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