ABSTRACT
PURPOSE: This study was undertaken to evaluate the clinical use of Bcl-2, c-Myc, and p53 oncoproteins, either singly or in combination, as prognostic discriminants relative to recurrence and overall survival in patients with Dukes B or C colorectal carcinoma. METHODS: Analyses were made on archival pathology tissues of 48 patients with colorectal cancer. The oncoproteins were localized using commercially available monoclonal antibodies: clone 124 for Bcl-2, 9E11 for c-Myc, and DO-7 for p53. The avidin-biotin peroxidase complex method was used. Patients were followed up for a period of 2 to 36 months. RESULTS: Expression of Bcl-2 and c-Myc was cytoplasmic, whereas nuclear p53 immunoreactivity was localized in the tumor cells. Sixty percent (29/48), 65 percent (31/48), and 37 percent (18/48) of the tumors showed overexpression of Bcl-2, c-Myc, and p53 oncoproteins, respectively. Fifty-four percent (18/33) and 100 percent (9/9) of moderately and poorly differentiated tumors, respectively, were positive for Bcl-2 (P < 0.01). No such correlation was noted for c-Myc and p53 oncoproteins. Univariate analysis showed that patients with Bcl-2 and c-Myc overexpression were associated with poorer overall survival than patients with Bcl-2-negative (P < 0.0124) and c-Myc-negative (P < 0.036) tumors. In addition, when patients were subgrouped according to Dukes stage, a statistically significant poorer overall survival was observed in Dukes C patients with Bcl-2-positive tumors (P < 0.017). Furthermore, multivariate analysis revealed that coexpression of three oncoproteins was predictive of a worse prognosis than for those individuals expressing none of the oncoproteins (P < 0.031) and only one positive oncoprotein (P < 0.014). CONCLUSION: These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.
Subject(s)
Carcinoma/pathology , Colonic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-myc/genetics , Rectal Neoplasms/pathology , Tumor Suppressor Protein p53/genetics , Adult , Aged , Analysis of Variance , Antibodies, Monoclonal , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Carcinoma/genetics , Cell Nucleus/metabolism , Cell Nucleus/ultrastructure , Colonic Neoplasms/genetics , Cytoplasm/metabolism , Cytoplasm/ultrastructure , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins c-bcl-2/analysis , Proto-Oncogene Proteins c-myc/analysis , Rectal Neoplasms/genetics , Survival Rate , Tumor Suppressor Protein p53/analysisABSTRACT
The antiestrogen tamoxifen (TAM) is an effective therapy for advanced breast cancer. However, its use is limited by the eventual development of acquired TAM resistance in many patients. There is now strong evidence to suggest that prolactin plays an important role in advanced breast cancer. We have measured plasma prolactin (PRL) and estrogen-receptor (ER) and progesterone-receptor (PR) in post-menopausal patients with breast cancer (Stage III, n = 44). The blood samples were collected pre-operatively and sequentially thereafter for a minimum period of 3 years or until the death of the patients. The ER and PR were estimated in breast tumor samples by dextran-coated charcoal (DCC) method. The patients were treated with surgery and radiotherapy followed by TAM (10 mg, 1 BD). Based on the response to treatments, the patients were divided into two groups: (1) TAM sensitive (n = 19) and (2) TAM resistant (n = 25). In the TAM sensitive group, patients responded to the treatment and did not develop progressive disease within a period of 3 years. On the contrary, in the group of TAM resistant, patients developed progressive disease within a period of 3 years. The development of progressive disease clearly indicated TAM resistance. Plasma PRL correlated well with the disease progression. This study clearly demonstrated that plasma prolactin accurately indicated the response and development of resistance to TAM in patients with advanced breast cancer.
Subject(s)
Breast Neoplasms/blood , Prolactin/blood , Tamoxifen/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Drug Resistance , Female , Humans , Middle Aged , Postmenopause , Treatment OutcomeABSTRACT
Circulating epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) were estimated in 58 patients with epithelial ovarian cancer and were correlated with clinically and biochemically important prognosticators. IGF-I levels were significantly low in patients as compared to controls. The relation of growth factors with clinically important prognosticators was non-significant. Moreover, the levels of EGF and IGF-I in the ER+/PR+ and ER-/PR- groups and in the low and high EGFR+ tumors did not differ significantly. Patients with EGF < 1.0 ng/ml had significantly better survival than those with EGF > 1.0 ng/ml.
