title: P16 but not retinoblastoma expression is related to clinical outcome in no-special-type triple-negative breast carcinomas.
abstract: Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types, including breast cancer. We investigated the association between Rb and p16 protein expression and clinical outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53 and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast carcinomas. Immunopositive p16 (p16+) and immunonegative Rb (Rb-) staining were seen in 49.5% and in 24.8% of tumors, respectively. There was an inverse correlation between p16+ and Rb- (P<0.001). P16+ was correlated with G3 grade (P<0.001), high Ki-67 (P=0.03), p53 overexpression (P<0.001) and CK5 immunopositivity (P=0.01). Rb- was not associated with any clinicopathologic variable. Follow-up and therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16+ nor Rb- immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with adjuvant chemotherapy, p16+ was associated with good response to therapy with significant increased disease-free survival (P=0.001) and showed a trend towards a statistical significance for increased overall survival (P=0.056); Rb- were not associated with disease-free survival and overall survival. In multivariate analysis, p16+ was independently associated with disease-free and overall survival, with a hazard ratio of 0.18 (95% CI: 0.06-0.51; P=0.001) and 0.21 (95% CI: 0.06-0.74; P=0.015), respectively. In patients with no-special-type triple-negative breast carcinomas, p16+ is related to good response to adjuvant chemotherapy and can be considered the best surrogate marker for Rb pathway loss.
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Giuseppe S
authors.initials: GS
authors.lastname: Bogina
authors.affiliation: Department of Oncology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lunardi
authors.affiliation: Department of Pathology, University of Verona, Verona, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Marcolini
authors.affiliation: Department of Pathology, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bortesi
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Marconi
authors.affiliation: Department of Oncology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Coati
authors.affiliation: Department of Oncology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Valerio
authors.affiliation: Department of Statistic, University of Verona, Verona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Guerriero
authors.affiliation: Department of Surgery, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Massocco
authors.affiliation: Department of Oncology, ULSS 5 Ovest Vicentino, Vicenza, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pegoraro
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein