| ObjectivePostoperative multimodality therapy for patients with breast cancerincluding adjuvant chemotherapy, hormone therapy, radiotherapy andothers can reduce the risk of recurrence and death in patients.Traditionally prognosis is determined by histolpgic and clinical factorssuch as the axillary node involvement, the tumor size, and SBR grading.However, these factors do not provide sufficient information foraccurate risk assessment of individual patients. Along with thedevelopment of the molecular biology more and more biologicalmarkers are revealed and applied in clinical and pathological practice.They are used in evaluating the prognosis and in selecting appropriatesystemic therapy for patients with breast cancer. In order to search formolecular markers which are closely related to prognosis for breastcancer and to provide more information for guiding treatment, thefollowing gene protein FHIT, CyclinDl, c-erbB-1, c-erbB-2, Bcl-2,Bax, ER, PR were studied, and their relevance to tumor biologicalcharacteristics, chemotherapy, diseases free survival (DFS) and overallsurvival (OS) of patients were analyzed.Materials and methods160 cases with breast cancer of the PLA General Hospital of China from 1998-2000 were collected and reviewed. According to the criteria of "China Histologic Typing of Breast Cancer 2000", a total of 100 cases of infiltrating ductal carcinoma with complete clinical and follow up data were enrolled in the study.Immunohistochemistry (SP method) was applied for detecting the expression of gene protein in paraffin embedded tissues. In situ hybridization was used to investigate the expression of c-erbB-2 mRNA in paraffin embedded tissues.ResultsThe mean age of the 100 patients with breast infiltrating ductal carcinoma was 49.49. The positive expression rates of gene proteins were as followings: ER 60%, PR 58%, c-erbB-1 32%, c-erbB-2 24%, FHIT 73%, CyclinDl 55%, Bcl-2 50%, Bax 34%. The positivities of ER increased in menopaused patients. c-erbB-2 showed a positive correlation to clinical stage (TNM), while ER, PR, FHIT, Bcl-2 presented a negative correlation to SBR grading.By univariant analysis, FHIT, CyclinDl, c-erbB-1, c-erbB-2, Bcl-2, ER, PR, axillary node status, clinical stage, SBR grading all showed significant correlation to prognosis. Patients with FHIT positive tumor had longer DPS and OS than those with FHIT negative tumor (Pdfs=0.0000, Pos=0.0000). Patients with Cyclin Dl positive tumor had longer OS than those with Cyclin Dl negative tumor (P=0.0053). Coexpression of Cyclin Dl and ER was significantly correlated withlonger DPS and OS (Pdfs=0.0108, Pos=0.0030). Overexpression of c-erbB-2 was significantly correlated with shorter DPS and OS. The same was to the overexpression of c-erbB-1 (Pdfs=0.000, POS=0.0008). Bcl-2 positive women had mean DFS of 83 months, mean OS of 124 months compared with 45 months and 75 months for Bcl-2 negative women. ER and PR positivity was significantly correlated with longer DFS (PER=0.0322, PPR=0.0129). Clinical stage (TNM), SBR, axillary node status were all significantly correlated with prognosis of patients.In Cox multivariant analysis FHIT (wald x2 =-2.91, P=0.004), ER (wald x2 =-1-3, P=0.194), Bcl-2 (wald x2 =-2.21, P=0.027), Bax (wald x2 =2.04, P=0.041), axillary node status (waldx2 =2.37, P=0.018), menopause or not (wald x2 =1.66, P=0.097) were independent prognostic indicators for DFS and c-erbB-2 (wald x2 =1.52, P=0.127),c-erbB-l (wald x2 =1.87, P=0.062), Bcl-2 (wald x2 =-1.5,P=0.134), axillary node status (wald x2 =2.15, P=0.032) showedsignificant effect on OS of breast infiltrating ductal carcinoma.For those patients received postoperative adjuvant chemotherapy, the expression of ER, PR, FHIT, Bcl-2 correlated to a better prognosis and longer DFS. On the other hand, the expression of c-erbB-1, c-erbB-2 indicated poor prognosis and shorter DFS.The patients with CyclinDl negative tumor, who received CAF, had a mean DPS of 51.6 months, mean OS of 57 mon... |
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