ERBB4 Expression in Ovarian Serous Carcinoma Resistant to Platinum-Based Therapy.
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories. Category frequencies were compared between tumor specimens vs controls using an unpaired t test. Among tumors, category frequencies were compared between CR and IR to chemotherapy. Overall survival (OS) was stratified by category. In total, 74 ovarian serous carcinoma samples (32 CRs and 42 IRs), 28 normal controls, and 16 ovarian cancer cell lines were evaluable. High-level ERBB4 expression was observed at a significantly higher frequency in ovarian serous carcinoma compared with normal control tissue. Among tumor specimens, ERBB4 expression was significantly higher for those with an IR to chemotherapy compared with CR (P = .033). OS was inversely correlated with ERBB4 expression levels. Median rates of OS were 18, 22, and 58 months among high-, intermediate-, and low-expression tumors, respectively. Our results indicate that ERBB4 expression by immunohistochemistry may correlate with chemotherapy-resistant ovarian serous carcinoma and shortened OS.
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL. Ozlen.Saglam@Moffitt.org.
Ozlen
O
Saglam
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Yin
Y
Xiong
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Douglas C
DC
Marchion
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Carolina
C
Strosberg
Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL.
Robert M
RM
Wenham
Department of Anatomic Pathology Moffitt Cancer Center, Tampa, FL.
Joseph J
JJ
Johnson
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Daryoush
D
Saeed-Vafa
Departments of Chemical Biology and Molecular Medicine, Translational Research Laboratory, Moffitt Cancer Center, Tampa, FL.
Christopher
C
Cubitt
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Ardeshir
A
Hakam
Department of Anatomic Pathology and the Moffitt Morsani Molecular Diagnostics Laboratory, Moffitt Cancer Center, Tampa, FL.
Anthony M
AM
Magliocco
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D066247:Receptor, ErbB-4 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016190:Carboplatin; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4; D002945:Cisplatin