title: ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study.
abstract: Aberrant expression of the epidermal growth factor receptor family has been implicated in the pathogenesis and progression of breast cancer and associated with poor prognosis. To evaluate the prognostic impact of the ErbB receptors expression profile, we analyzed a well-characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor (EGFR/HER-1), ErbB-2 (HER-2), ErbB-3 (HER-3), and ErbB-4 (HER-4), using immunohistochemistry. Tumors were considered negative or positive for each marker when less than or more than 25% of the cancer cells were immunopositive. Expression of EGFR, ErbB-2, ErbB-3, and ErbB-4 was observed in 31 (21.4%), 65 (44.8%), 72 (49.7%), and 81 (55.9%) of the cases, respectively. There were significant associations between EGFR expression and pT status (P = 0.01), and between ErbB-3 expression and pN (P = 0.003), menopausal (P = 0.01) and PR (P < 0.001) status. The majority of the cases co-expressed two or more receptors. ErbB-3 resulted positive in 51/81 (63.0%) of the ErbB-4 positive cases and ErbB-3/ErbB-4 co-expression was statistically significant (P = 0.0003). As expected, ErbB-2 expression was associated with reduced overall survival at 15 years of follow-up (P = 0.04), even after adjusting for a series of other prognostic factors (P = 0.05). Moreover, cumulative analysis of ErbB-2/3/4 expression showed a strong positive association between higher total ErbB-2/3/4 expression score and worse prognosis (P = 0.002). The simultaneous expression in cancer cells of more than one ErbB receptor identifies a subset of breast cancer patients at high risk for poor survival.
authors.affiliation: Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Calogero
authors.initials: C
authors.lastname: Saieva
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Mancini
authors.forename: Ramona
authors.initials: R
authors.lastname: Lupi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Noviello
authors.forename: Jasminka
authors.initials: J
authors.lastname: Omerovic
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Vania
authors.initials: V
authors.lastname: Vezzosi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Alimandi
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality*; D002277:Carcinoma / Q000378:metabolism*; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D017978:Receptors, Growth Factor