SERUM NITRIC OXIDE (NO), TUMOR NECROSIS FACTOR-ALPHA (TNF- α), BASIC FIBROBLAST GROWTH FACTOR (b-FGF) AND COPPER AS PROGNOSTIC AND ANGIOGENIC MARKERS IN BREAST CANCER PATIENTS

Abstract

Breast cancer is the most frequent neoplasm in women and the most frequent cause of death in women between 35 and 55 years of age. Its incidence is increasing in all industrialized countries. The major cause of death from breast cancer is not the primary tumor but it is the metastasis of the disease from the primary tumor site to distant sites in body including the lung, bone and brain. Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. The angiogenic phenotype of breast carcinoma, as in other tumors, is acquired early in tumorigenesis while the tumor is still in situ.

In this study, our aim was to compare the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumor necrosis factor-alpha (TNF-a), basic fibroblast growth factor (bFGF) and copper with those of serum CAl 5-3 as the standard tumor marker in breast cancer patients.

Fourty-five subjects were included in this study. They were divided into two groups:

Group 1: It included 15 nonnal control subjects premenopausal female volunteers of comparable age.

Group II:

It included 30 premenopausal female patients with breast cancer.

All of the angiogenic serum factors : nitric oxide (NO), tumor necrosis factor-alpha (TNF-a), basic fibroblast growth factor (bFGF) and copper were measured in serum samples collected from the normal control subjects (n=15) once and from the premenopausal breast cancer females (n=30, before surgery, 2 weeks following surgical removal of the breast and after 6 cycles ofFAC treatment [5-Fluorouracil (F) 500 mg/m2, Adriamycin (A) 50 mg/m2 and Cyclophosphamide (C) 500 mg/m2]. Tumor microvessel density (MVD) was counted using light microscopy after immunostaining of tissue sections with antibodies to the endothelial cell antigen CD31. - After surgery a biopsy of affected breast tumor tissue was taken for clinicopathological parameters examination including lymph node involvement estrogen receptor, progesterone receptor ,tumor size, tumor pathological grade and patient clinical stage. Also, a tumor tissue was fixed by formalin and embedded by paraffin for immunohistochemical staining of CD31 located in the endothelial cells of tumor blood vessels for counting of the blood vessels. The diagnostic values of the assayed serum parameters were compared using the Receiver Operating Characteristic (ROC) curve analysis to compare the diagnostic values of five assayed parameters, giving that the higher ROC value corresponds to the more better diagnostic marker. •

Results of tumor MVD

- Regarding tumor MVD, our result showed a significant difference between normal breast tissue adjacent to breast tumor mass and the breast tumor mass. Also, tumor MVD was found to be significantly correlated with tumor size and pathological grade, patient clinical stage and lymph node involvement.