Abstract
BackgroundPlatinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer.MethodsFresh surgical biopsy specimens were obtained from 30 patients with primary or recurrent peritoneal carcinomatosis from ovarian cancer. ERCC1, GSTP1, MGMT, XPD, and BRCA1 gene expression levels were determined by Real-Time RT-PCR. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.ResultsMGMT and XPD expression was directly and significantly related to resistance to platinum-containing treatment (p = 0.036 and p = 0.043, respectively). Significant predictivity in terms of sensitivity and resistance was observed for MGMT expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity of resistance (90.9%) but very low predictivity of sensitivity (37.5%) (p = 0.06) were observed for XPD. The best overall and significant predictivity was observed for chemosensitivity test results (85.7% sensitivity and 91.3% resistance; p = 0.0003).ConclusionsThe in vitro assay showed a consistency with results observed in vivo in 27 out of the 30 patients analyzed. Sensitivity and resistance profiles of different drugs used in vivo would therefore seem to be better defined by the in vitro chemosensitivity test than by expression levels of markers.
Highlights
Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world
Patients Thirty-two patients with peritoneal carcinomatosis from primary advanced (7 cases) or recurrent (25 cases) ovarian cancer were recruited for the in vitro chemosensitivity assay and for analysis of biomarkers potentially predictive of resistance to platinum compounds
Significant predictivity in terms of sensitivity and resistance to the different cisplatin-based regimens was observed for methylguanine-DNA methyltransferase (MGMT) expression (75.0% and 72.5%, respectively; p = 0.03), while high predictivity with regard to resistance (90.9%), but very low predictivity in terms of sensitivity (37.5%) (p = 0.06) were observed for Xeroderma pigmentosum group D (XPD)
Summary
Platinum-based regimens are the treatments of choice in ovarian cancer, which remains the leading cause of death from gynecological malignancies in the Western world. The aim of the present study was to compare the advantages and limits of a conventional chemosensitivity test with those of new biomolecular markers in predicting response to platinum regimens in a series of patients with peritoneal carcinomatosis from ovarian cancer. Patients with the same tumor histotype, especially in solid malignancies, often respond differently to the same chemotherapy regimen due to intertumor heterogeneity Despite knowledge of such heterogeneity, chemotherapy is still largely empirically planned, and the acquisition of. Such a goal was intensively pursued in the 1980s by American and European research groups who developed a number of chemosensitivity tests using fresh material from human tumors and based on the determination of cell proliferation (clonogenic potential and 3Hthymidine incorporation) or total cell evaluation (dye exclusion, sulphorhodamine blue, MTT assay and ATP bioluminescence) [1,2,3,4,5,6]. With the advent of molecular biology at the end of the nineties, attention moved towards the search for molecular and genetic markers involved in proliferation and DNA repair processes that might be predictive of response to both conventional cytotoxic and target therapy drugs [11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call