Tumor Histology and Stage but Not p53, Her2-neu or Cathepsin-D Expression are Independent Prognostic Factors in Breast Cancer Patients

• Published in: Anticancer research Vol. 24; no. 3B; pp. 2061 - 2068
• Main Authors: KORKOLIS, D. P, TSOLI, E, ASIMACOPOULOS, P, GORGOULIS, V. G, FOUSKAKIS, D, YIOTIS, J, KOULLIAS, G. J, GIANNOPOULOS, D, PAPALAMBROS, E, NIKITEAS, N. I, SPILIOPOULOU, C. A, PATSOURIS, E
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.05.2004
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cathepsin D - biosynthesis; Disease-Free Survival; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Lymph Nodes - pathology; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Staging; Proportional Hazards Models; Receptor, ErbB-2 - biosynthesis; Receptors, Estrogen - biosynthesis; Receptors, Progesterone - biosynthesis; Survival Analysis; Tumor Suppressor Protein p53 - biosynthesis; Tumors; Human; Prognosis; Enzyme; Her2-neu; Histology; Breast cancer; Malignant tumor; Survival; p53; Mammary gland diseases; Peptidases; TP53 Gene; C-Onc gene; Hydrolases; Aspartic endopeptidases; Cathepsin D; Mammary gland; Tumor suppressor gene
• ISSN: 0250-7005; 1791-7530

Background: Several factors are currently employed for prognosis assessment and treatment determination in breast cancer. An array of molecular parameters, such as p53, Her2-neu (c-erbB 2) and Cathepsin-D, are also examined to improve clinical patient management. We have conducted a statistically powerful study of the prognostic value of conventional factors and of the investigational factors p53, Her2-neu and Cathepsin-D in patients with invasive breast carcinoma, in order to compare their significance. Our analysis was extended to determine the associations of p53 and Her2-neu with risk of death and relapse among patients with and without lymph node metastases. Materials and Methods: In a set of 125 primary breast tumors, p53 and Her2-neu expression were immunohistochemically evaluated. Cathepsin-D, estrogen and progesterone receptor concentrations were determined in cytosols by a standard immunoradiometric assay. Results: Over a mean of 62 months, 49 patients (39%) had a relapse and 29 patients (23%) died. Overexpression of p53, Her2-neu and Cathepsin-D was observed in 31%, 46% and 88% of cases, respectively. Overall survival was associated with histology (hazard ratio 0.04, 95% confidence interval: 0.01, 0.49 for lobular tumors) and stage (hazard ratio 5.94, 95% confidence interval: 1.30, 27.15 for stage III samples). Disease-free survival was also related to histology (hazard ratio 0.23, 95% confidence interval: 0.08, 0.73 for lobular tumors) and stage (hazard ratio 4.27, 95% confidence interval: 1.36, 13.36 for stage III tumors). Patients with both negative nodal status and Her2-neu overexpression tended to display an elevated risk of death. Conclusion: Our results support the prognostic power of tumor histology and stage and emphasize the need for further studies on the prognostic impact of p53, Her2-neu and Cathepsin-D in breast cancer. Additionally, our analysis indicates that deregulation of Her2-neu might characterize a subgroup of node-negative patients with poor prognosis who could benefit from an aggressive adjuvant therapy.