Prognostic significance of immunohistochemically localized biomarkers in stage II and stage III breast cancer: a multivariate analysis

• Published in: Annals of surgical oncology 2000-05, Vol.7 (4), p.305-311
• Main Authors: Bhatavdekar, J M, Patel, D D, Shah, N G, Vora, H H, Suthar, T P, Chikhlikar, P R, Ghosh, N, Trivedi, T I
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens; Bcl-2 protein; Biomarkers; Biomarkers, Tumor - metabolism; Biotin; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; CD44 antigen; Coagulation factors; Female; Humans; Immunohistochemistry; Lymph nodes; Medical prognosis; Middle Aged; Multivariate Analysis; Neoplasm Staging; p53 Protein; Peroxidase; Phenotypes; Prognosis; Prolactin; Proto-Oncogene Proteins c-bcl-2 - metabolism; Regression Analysis; Streptavidin; Survival; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1007/s10434-000-0305-5

The aim was to investigate the expression of a panel of biomarkers such as prolactin (PRL), p53, Bcl-2, c-erb B2, Ki-67, CD44, and factor VIII-related antigen (FVIII-RA) in primary tumors of stage II and stage III breast cancer and its correlation with disease prognostication. The streptavidin-biotin peroxidase complex technique was used for the detection of these antigens. Cytoplasmic staining pattern was observed for PRL, Bcl-2, and Ki-67. Staining pattern for p53 was nuclear. Membranous and/or cytoplasmic staining was noted for c-erb B2 and CD44. Microvessel staining was noted for FVIII-RA. Of the 93 primary breast tumors analyzed, positivity for PRL was noted in 82%, for p53 in 56%, for Bcl-2 in 73%, for c-erb B2 in 68%, and for Ki-67 and CD44 in 78% each. The microvessel count (MVC) for FVIII-RA ranged from 0.0 to 29.0, with a median of 6.0, which was used as a cutoff. MVC > or = 6.0 was noted in 51% of breast tumors. With increasing tumor size, the higher frequency of positivity of MVC > or = 6.0 (P = .0001), CD44 (P = .001), PRL (P = .002), and c-erb B2 (P = .008), and higher frequency of Bcl-2 negativity (P = .033), was noted. In stage III patients, a higher positivity of the following biomarkers was noted, compared with stage II patients: MVC > or = 6.0 (P = .0004), PRL (P = .0002), c-erb B2 (P = .001), and CD44 (P = .005). Further, Bcl-2 positivity was significantly lower in patients with stage III disease compared with those with stage II disease (P = .024). In patients with nodal involvement, the frequency of c-erb B2 (P = .006), MVC > or = 6.0 (P = .011), and PRL (P = .032) was higher than in those without nodal involvement. Moreover, in these patients, with the increase in the number of involved lymph nodes, there was a significant increase in frequency of CD44+ (P = .0004) and PRL+ (P = .013) tumors. Abnormal expression of one biomarker was seen in 7% of tumors, of two biomarkers in 4%, of three in 15%, of four in 19%, of five in 28%, of six in 20%, and of all seven biomarkers in 7% of tumors. The frequency of an increasing number of biomarkers coexpressed was higher in stage III patients compared with stage II patients (P = .00003). In the total number of patients (n = 93), tumors with Bcl-2 negativity (P = .00001), MVC > or = 6.0 (P = .001), PRL positivity (P = .02), and CD44 positivity (P = .034) had a significantly poorer overall survival (OS) compared with their respective counterparts. In stage II patients (n = 40), only p53 expression