title: Mitotic index in the subrenal capsule assay as an indicator of the chemosensitivity of ovarian cancer.
abstract: The subrenal capsule assay (SRCA) is used in clinical oncology to assess the sensitivity of individual malignant tumors to various anticancer agents and their combinations. Mitotic indices reflect cancer cell proliferation and have prognostic value in epithelial neoplasms, including ovarian carcinoma. We combined the two tests (SRCA, mitotic index) by evaluating the numbers of mitotic figures per square millimeter of neoplastic epithelium (M/V) in paraffin-embedded tumor samples after SRCA. The M/V index was compared with the tumor size measurement (dTS), which is used in conventional SRCA to predict the drug response. Histology examination showed insignificant changes in the size of tumor transplants due to host reaction but disclosed a number of potential errors in the use of dTS to evaluate transplant growth and drug effects. In our series of 62 patients with advanced ovarian carcinoma the M/V value was superior to the dTS in explaining the clinical response after 6 months as assessed at second-look laparotomy. Patients showing no response had significantly higher M/V values than did those displaying complete or partial responses (P < 0.033). The use of 6 mitotic figures/mm2 as a limit differentiating responders from nonresponders resulted in an overall predictive accuracy of 79% in the logistic regression analysis. In comparison to the FIGO stage, residual tumor size, and the dTS, the M/V value obtained for the cytostatic combination given to the patient was the single most significant factor predicting the 6-month clinical response. The results indicate that the combined use of the M/V index and SRCA is a promising new approach to prediction of the drug response in ovarian adenocarcinoma.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Suonio
authors.forename: P
authors.initials: P
authors.lastname: Lipponen
authors.forename: J
authors.initials: J
authors.lastname: Mäenpää
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
authors.forename: L
authors.initials: L
authors.lastname: Kangas
authors.forename: L
authors.initials: L
authors.lastname: Tuomisto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016015:Logistic Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008940:Mitotic Index; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D013370:Subrenal Capsule Assay
chemical_list: D000970:Antineoplastic Agents