title: TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.
abstract: ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.
authors.affiliation: Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, ul. Roentgena 5, Warsaw 02-781, Poland. jkupry@coi.waw.pl
authors.forename: J
authors.initials: J
authors.lastname: Kupryjańczyk
authors.forename: R
authors.initials: R
authors.lastname: Madry
authors.forename: J
authors.initials: J
authors.lastname: Plisiecka-Hałasa
authors.forename: J
authors.initials: J
authors.lastname: Bar
authors.forename: E
authors.initials: E
authors.lastname: Kraszewska
authors.forename: I
authors.initials: I
authors.lastname: Ziółkowska
authors.forename: A
authors.initials: A
authors.lastname: Timorek
authors.forename: J
authors.initials: J
authors.lastname: Stelmachów
authors.forename: J
authors.initials: J
authors.lastname: Emerich
authors.forename: M
authors.initials: M
authors.lastname: Jedryka
authors.forename: A
authors.initials: A
authors.lastname: Płuzańska
authors.forename: I
authors.initials: I
authors.lastname: Rzepka-Górska
authors.forename: K
authors.initials: K
authors.lastname: Urbański
authors.forename: J
authors.initials: J
authors.lastname: Zieliński
authors.forename: J
authors.initials: J
authors.lastname: Markowska
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D000939:Epitopes / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D009944:Organoplatinum Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53