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LeY Antigen Expression Promotes Activation Of Epidermal Growth Factor Receptor And The Correlates With Prognosis Of Breast Cancer

Posted on:2008-12-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:2144360212484110Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective: Blood group antigens appear to play an important role in cell recognition, differentiation, and growth regulation. During the process of malignant transformation, these antigens undergo various alterations. LeY antigen is a difucosylated oligosaccharide which belongs to the human blood group family occures as the sugar chains on glycolipid and glycoprotens. Under physiological conditions, the expression of LeY on adult tissue is restricted to the epithelial surfaces. However, LeY is overexpressed in the majority of carcinomas, including breast, ovary, pancreas, prostate, colon, and non-small cell lung cancers. Strong expression of the LeY antigen may be associated with the clinically aggressive progression and the behavior of the malignants. LeY has been recognized as a tumor-associated carbohydrate antigen.Epidermal growth factor receptor (EGFR) is a number of the ErbB family. The extensive expression of EGFR is associated with the poor neoplastic cell differentiation, the development of distant metastases and the worse prognosis. After the activating of the EGFR on the cell surface, it is found to induce EGFR phosphorylation and activate tyrosine kinase, and then activate the intracellular signal transduction which can enhance the cell proliferation, inhibit cell apoptosis and facilitate the tumor invasion and metastasis.This study investigates the expressions of LeY, EGFR and pEGFR in breast cancer with the clincal parameters and to analyse the relationship among these factors. It will be significant in providing the preliminary datafor prognosis of breast cancer.Methods: Immunohistochemical detection of LeY, EGFR and pEGFR were performed on 104 paraffin embedded operable breast cancer specimens using a streptavidin-biotin peroxidase technique. 62 patients were followed up and got the whole related data. According to the patients'age, menopausal status, size of tumor, histological grade, lymph node status, Nottingham prognostic index (NPI), clinical stage, ER status and HER-2 status, these specimens were divided into different groups.All immunostained tissue was evaluated using the histochemical score. Statistical analysis of data was performed using SPSS package version 11.5. The significance of associations was determined by means of the Pearson R test and/or Pearson chi-square tests. In survival analysis, Kaplan-Meier curves were derived and the statistical significance of the differences in survival was determined using the Log-rank test. P value of <0.05 were identified as statistically significant.Results:1. Expression of LeY antigen, EGFR, pEGFR in breast cancer. The staining observed of LeY antigen was predominantly localized to the cell membrane. Of the breast cancer, 20% were negative for LeY expression. A variable percentage of positively staining tumor cells was observed among the remaining 80% breast cancer; 23% showed a weak expression, 27% showed moderate expression, 30% showed strong expression of LeY and 57% showed overexpression totally. EGFR and pEGFR was also predominantly localized to the cell membrane and cytoplasm. 76% were positive for EGFR expression. 34% showed a low level of expression and 42% showed extensive expression of EGFR. In addition, 80% were positive for pEGFR expression. 24% showed a low level of expression and 56% showed extensive expression of pEGFR on the cell membrane and cytoplasm.2. Correlations among LeY antigen, EGFR, pEGFR in breast cancer. There were positive correlations between LeY antigen and EGFR, LeY antigen and pEGFR, EGFR and pEGFR. Their correlation coeffients were 0.592, 0.646 and 0.566 respectively (p <0.01).3. Correlation between LeY antigen, EGFR, pEGFR and the clinical parameters of breast cancer. The expression of LeY antigen was closelyrelated to the size of tumor, histological grading, the NPI, the ER status and the expression of HER-2 (p<0.05). The relationship with the age, the menopausal status, lymph node status and clinical stage was not obvious. Only NPI significant was observed with EGFR expression (p<0.05). It was different expression in the premenopausal and postmenopausal group in pEGFR expression. Its expression was associated with the size of tumor, histological grading, the NPI and the HER-2 status.4. The relationship between disease free survial of breast cancer and the different expression of LeY antigen, EGFR, pEGFR. The extensive expression of LeY antigen was found negatively related to disease free survival (Log-rank=4.11, p <0.05). The media disease free survival of LeY with the extensive expression group was about 44 months, whereas 59 months in low or none LeY expression group. The significant differences weren't found in the different expression groups of EGFR and pEGFR.Conclusion:1. The up-regulated expression of LeY antigen was found in breast cancer. The expressions of the LeY antigen showed significant difference in the size of tumor, histological grading, the NPI, the ER status and the HER-2 status.2. The up-regulated and expression of EGFR and pEGFR were found in breast cancer. EGFR expression only correlated in the NPI. The expression of pEGFR was different in the menopausal status, the size of tumor, histological grading, the NPI and the HER-2 status. pEGFR may be a better prognostic factor of breast cancer than EGFR.3. There was positive correlation among LeY antigen, EGFR, and pEGFR, may suggest the consistent function of LeY and EGFR, especially the LeY and pEGFR indicats that the overexpressing of LeY antigen may activate epidermal growth factor receptor.4. The overexpression of LeY was associated with the decrease survival of DFS in breast cancer whereas EGFR and pEGFR were negative.
Keywords/Search Tags:LeY antigen, EGFR, phosphor-EGFR, breast cancer, prognosis
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