title: Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between "triple-negative" and non-"triple-negative" tumors.
abstract: Bcl-2 is a tumorigenic protein that is expressed in 25% to 50% of breast cancers. Although its expression has been widely accepted as a favorable prognostic marker, its protective mechanism of action remains unclear. "Triple-negative" tumors are an aggressive subgroup known to carry a poor prognosis. Studies documenting prognostic significance of Bcl-2 expression in triple-negative in comparison to non-triple-negative breast cancers are limited. Bcl-2 expression was correlated with tumor size, grade, histologic type, lymphovascular invasion, lymph node status, patients' overall survival, estrogen receptor, progesterone receptor, Her-2, p53, and epidermal growth factor receptor in 124 triple-negative and 458 non-triple-negative tumors. There were significant differences between triple-negative and non-triple-negative tumors in their relationship to Bcl-2 expression (81% versus 29%, respectively) and tumor aggression. As previously reported, in non-triple-negative tumors, Bcl-2 positivity correlated with less aggressive tumors (94% of grade I tumors were Bcl-2+ versus 62% of grade III tumors, P < .011) and overall survival (P = .008). However, the opposite was true in patients with triple-negative tumors, where Bcl-2 positivity was associated with poorer survival (P = .64). In triple-negative tumors, Bcl-2 positivity was not associated with any of the aforementioned parameters except for a lower incidence of lymph node metastasis. Moreover, by Cox regression analysis of all variables, in patients with triple-negative tumors, lymphovascular invasion (P = .009) and Bcl-2 expression (P = .028) were predictors of poor survival. In conclusion, there are major clinicopathologic differences between breast cancer phenotypes. Our results establish the value of using Bcl-2 in prognostic stratification of patients and its potential therapeutic implications in selecting patients for treatment.
authors.affiliation: Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS 66160, USA.
authors.forename: Kareem
authors.initials: K
authors.lastname: Tawfik
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Davis
authors.forename: Fang
authors.initials: F
authors.lastname: Fan
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D046228:Microarray Analysis; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary; D010641:Phenotype; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human