Analysis of Morphological immunoistochemical and genetic prognostic detyerminants in prediciting disease

Abstract

Breast cancer is an increasingly important cause of illness and death among women worldwide. In Pakistan also breast cancer is not only the commonest malignancy among women but it is occurs in a younger age as compared to western population. This study was conducted on 315 consecutive human breast biopsy and mastectomy specimen with lymph node sampling and histologically proven ductal carcinoma breast. The objective was to assess the utility of novel establish prognostic markers that will reliably assess the outcome of disease in breast carcinoma. Established parameters and prognostic variables of breast cancer like age of the patient, menstrual status, tumor size, histological grade of tumor, axillary lymph node status (distant metastases if any), Hormones Receptor (estrogen and progesterone) status were studied in parallel to novel prognostic markers like amplification of growth promoting genes / deletion of tumor suppresser genes (Cerb B-2, EGFR and p53), tumor proliferative index (PCNA), and Cathepsin-D. Analysis was done on a total number of 315 patients. The mean age was found to be 49 years while median was 48 years. Axillary lymph nodes positivity was seen in 170 (54%) cases. Mean tumor size was 4.16 cms (range 0.5-22 cms). Histologically grade II tumors comprised 214 (68%) cases, followed by grade III 56 (18%) and grade I 45 (14%) cases. Vascular /lymphatic invasion was seen in 150 (48%) cases. A statistically significant difference was found in overall and disease free survival of patients when there was an amplification and/or over expression of C-erbB-2, EGFR, p53 and with PCNA reactivity of >25%. p53 positivity was seen in 55.23% of the cases, CerbB-2 in 39.36%, EGFR in 22%. P53, C-erbB-2 and EGFR showed significant correlation with histological grade, tumor size, axillary lymph nodes, local recurrence,4 distant metastases and ER/PgR status (p <0.05). C-erbB-2 positive patients also showed resistance to chemotherapy (p<0.05). p53 and EGFR also showed significant correlation with vascular/lymphatic invasion (p<0.05). PCNA >25% was significantly correlated with histological grade, tumor size, vascular/lymphatic invasion and distant metastases. Cathepsin-D protein over expression was seen in 39% of the cases. Its over expression did nct show any significant correlation with overall survival or disease free survival. In this study we have shown that C-erbB-2, EGFR, p53 are independent prognostic markers in both univariate and multivariate analysis. According to our study Cathepsin-D over-expression was not a good prognostic marker if only expression in tumor cells is taken into account.