The clinical predictivity of biomarkers of stage III-IV epithelial ovarian cancer in a prospective randomized treatment protocol.
BACKGROUND
The aim of this study was to define the clinical relevance of functional biomarkers, prospectively assessed in a randomized clinical protocol, in patients with Stage III-IV epithelial ovarian cancer. The protocol compared cisplatin with polychemotherapy that included cisplatin and cyclophosphamide.


METHODS
In a subset of 168 patients with invasive epithelial ovarian cancer cell proliferation was determined by the 3H-thymidine labeling index, DNA ploidy was assessed by flow cytometry, and the expression of p53, bcl-2, and glutathione S-transferase-pi (GST-pi) was evaluated by immunohistochemistry using the antibodies PAb1801, anti-bcl-2, and GST-pi, respectively.


RESULTS
Cell proliferation, DNA ploidy, and the expression of p53, bcl-2, and GST-pi were generally unrelated to one another and unrelated to clinicopathologic features, except for an association between DNA ploidy and the rate of cell proliferation. All biologic variables except bcl-2 were slightly related to tumor grade. DNA ploidy emerged as a predictor of clinical complete response and 3-year overall survival, regardless of treatment type or residual disease. Conversely, except for a favorable outcome for patients with tumors not expressing bcl-2 who were treated with cisplatin, no definitive patterns of predictivity for short term or long term clinical outcomes were observed for the other biomarkers studied.


CONCLUSIONS
DNA ploidy appears to be the most clinically relevant biomarker for epithelial ovarian cancer. More information is needed to understand the role of the other markers studied in this tumor type.
Silvestrini
R
R
Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Daidone
M G
MG
Veneroni
S
S
Benini
E
E
Scarfone
G
G
Zanaboni
F
F
Villa
A
A
Presti
M
M
Danese
S
S
Bolis
G
G
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D004247:DNA / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011003:Ploidies; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D019275:Radiopharmaceuticals; D012074:Remission Induction; D015996:Survival Rate; D013936:Thymidine; D016896:Treatment Outcome; D014316:Tritium; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; D014316:Tritium; D003520:Cyclophosphamide; D004247:DNA; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D002945:Cisplatin; D013936:Thymidine