Association of ErbB1–4 expression in invasive breast cancer with clinicopathological characteristics and prognosis

• Published in: Breast cancer (Tokyo, Japan) Vol. 21; no. 4; pp. 472 - 481
• Main Authors: Fujiwara, Saori, Ibusuki, Mutsuko, Yamamoto, Satoko, Yamamoto, Yutaka, Iwase, Hirotaka
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2014; Springer
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer patients; Cancer Research; Epidermal growth factor; Estrogen; Female; Follow-Up Studies; Fulvestrant; Gene Dosage; Genetic research; Humans; Immunoenzyme Techniques; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Oncology; Original Article; Progesterone; Prognosis; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - genetics; Receptor, ErbB-3 - metabolism; Receptor, ErbB-4 - genetics; Receptor, ErbB-4 - metabolism; Receptors, Estrogen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - genetics; Surgery; Surgical Oncology; Survival Rate; Young Adult; Prognosis; Copy number; ErbB family; mRNA expression
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-012-0415-5

Background Human epidermal growth factor receptor type 2 (Her2)/ErbB2 plays a key role in the initiation and progression of invasive breast cancer. However, the prognostic relevance to breast cancer patients of the other ErbB family members has long been a matter of debate. Methods In a series of 250 primary invasive breast cancer patients, we performed a comprehensive analysis of ErbB1–4 at the levels of mRNA expression and gene copy number using real-time quantitative PCR. The relationship between the status of ErbB1–4 and the clinicopathological characteristics or prognosis was evaluated. Results The mRNA expression of ErbB2, but not the other ErbB genes, was significantly correlated to copy number ( P  = 0.0005). ErbB3 and ErbB4 mRNA expression were positively correlated to each other ( P  < 0.0001). The mRNA expression of ErbB1/2 was inversely correlated to estrogen receptor (ER) and progesterone receptor (PgR) positivity, although mRNA expression of ErbB3/4 was positively correlated to ER and PgR positivity. Kaplan-Meier survival analysis showed that ErbB1 mRNA expression was associated with reduced survival. Neither ErbB2 nor ErbB3 mRNA expression had any association with survival, because half of the patients with Her2-positive tumors were treated with trastuzumab. High ErbB4 mRNA expression showed good prognosis with respect to breast cancer-specific survival Conclusions ErbB3 and ErbB4 mRNA expression, as well as well as that of ErbB1 and ErbB2, could be histopathological factors. ErbB3 mRNA was highly expressed in ER-positive tumors and has controversial prognostic value. ErbB4 mRNA expression was well correlated with ER positivity and good prognosis, indicating that ErbB4 may contribute to ER-dependent growth.