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Breast Cancer ER, PR, CerbB-2, P53, P16 Expression And Prognostic Factors

Posted on:2011-03-14Degree:MasterType:Thesis
Country:ChinaCandidate:S Y WeiFull Text:PDF
GTID:2144360305952435Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
ObjectiveBreast cancer is one of the world's most common malignant tumor. Worldwide incidence increased year by year. Breast cancer incidence grows significantly in our country, especially in large cities it becomes the first women incidence of malignant tumors. After years of study, although the progress of breast cancer diagnostic research has greatly improved, it is still not ideal of how to accurately assess the prognosis of breast cancer and to provide reliable basis for clinical treatment. In 1971, it was found estrogen receptor (ER) exists in some breast cancer cells. In the subsequent long-term tracking study found that, ER's overexpression has some relevance with breast cancer. Progesterone receptor (PR) is the estrogen and androgen receptor-induced products. PR in the presence of progesterone, can inhibit the growth of breast cancer cell lines and inhibit tumor cell invasion and metastasis. PR-positive means the high efficient of endocrine therapy, and the prognosis is better. CerbB-2,an original oncogene, is found in the closest relationship with breast cancer. CerbB-2 is in non-activated state under normal circumstances, when under the influence of external factors within the activation, we can by gene amplification and protein over expression, stimulate cell proliferation, invasion and metastasis. Therefore, CerbB-2 overexpression on cell surface is a tumor transforming activity. P53 tumor suppressor genes are found in human tumors so far, the most relevant genes, in normal conditions can inhibit tumor. P53 protein into wild type and mutant, the mutation has not only lost their proliferation and differentiation of negative regulation, but also activate some positive growth-promoting gene expression, thus promoting cell proliferation,and leading to tumors. P16 is an important tumor suppressor gene. Occurs when the P16 deletion mutant, transcription and expression abnormalities, the obstacles of P16 protein synthesis induced cell proliferation out of control, resulting in tumorigenesis. These results suggest that ER, PR, CerbB-2, P53, P16 in breast cancer with overexpression of their breast cancer prognosis. However, single test of these indicators has always had some limitations. Detection of breast cancer paraffin blocks ER, PR, CerbB-2, P53, P16 expression, the expression of tissue pathological type of breast cancer, histological grade, tumor metastasis, patient age, tumor size correlation. Therefor, it is necessary to disscuss the significance in the combined detection of ER, PR, CerbB-2, P53, P16 in breast cancer diagnosis and prognosis.HER-2 breast cancer gene amplification is the main mechanism of CerbB-2 protein overexpression. It is important to define HER-2 gene and protein status in assessing the prognosis of breast cancer, and help to guide the transfer of breast cancer and HER-2 over-expression or amplification of Herceptin treatment of patients. There are many ways to detect HER-2,and which is the best has become the central issue of research. Immunohistochemistry (IHC) detedts the expression of HER-2 protein on the cell surface by HER-2 specific antibodies. The results in the detection process are affected easily by a variety of external factors, it is undeniable that IHC is simple, inexpensive, good repeatability, the material ask for few, in clinical practice can be widely used. Fluorescence in situ hybridization (FISH) is a new diagnosis technology in breast cancer which is used to detect the centromere on chromosome 17 and HER-2 gene amplification.Materials and methods1. collected breast cancer tissue after removal of paraffin as the experimental subjects, patients were not receiving preoperative radiotherapy or chemotherapy treatment.2. two-step immunohistochemistry detection of breast cancer tissue paraffin blocks ER, PR, CerbB-2, P53, P16 expression.3. analysis of expression levels in breast tissue pathological type, histological grade, tumor metastasis, patient age, tumor size correlation.4. collected breast cancer tissue after removal of paraffin as the experimental subjects, patients had not received preoperative radiotherapy or chemotherapy treatment.5. two-step immunohistochemical detection of breast cancer CerbB-2 expression.6. detected by fluorescence in situ hybridization HER-2 gene amplification.7. the results of the two detection methods were compared.Results1. ER, PR expression in breast cancer pathology, histological grade, lymph node metastasis, age, no correlation between tumor size.2. breast cancer gradeâ… ,â…¡,â…¢grade in, ER positive expression rate (68.75%), (63.95%), (60.61%), PR positive expression rate (75.00%), (65.12%), (57.58%). Both with the histological grade of the rises.3. in different pathological types of breast cancer CerbB-2 positive expression was not statistically significant.4. CerbB-2 in lymph node metastasis in primary breast tumors positive rate 78.57%, significantly higher than those without lymph node metastasis of breast primary tumor in the positive rate of 55.00 percent, the difference was statistically significant.5. breast cancerâ… ,â…¡,â…¢grade CerbB-2 positive rate was 43.75%, 47.77%,77.27% was statistically significant. CerbB-2 with cell differentiation becomes worse and gradually increased its expression.6. CerbB-2 positive expression rate and size of tumor, tumor size increased, the positive rate increased.7. ER and PR expression and CerbB-2 was negative.8. this group of patients with breast cancer in the expression of P53 pathological type, histological grade, patient age, tumor size had no significant relationship.9. P53 in the breast with lymph node metastasis in primary tumors was significantly higher than those without lymph node metastasis in primary breast tumors positive rate, the difference was significant.10. this group of patients with breast cancer in the expression of P16 pathological type, histological grade, patient age, nothing obvious relationship between tumor size.11. P16 with lymph node metastasis of breast primary tumor in the positive rate was significantly lower than those without lymph node metastases from breast primary tumors, the positive rate, the difference was significant.12. CerbB-2 protein expression was negative and weak positive there was no amplification of HER-2 gene.13. CerbB-2 protein was (++) and (+++) expression of the samples, HER-2 gene amplification, but still part of the HER-2 gene without amplification. Conclusions1. and the detection of breast cancer patients with ER, PR, CerbB-2, P53, P16 level can be found, according to ER, PR, CerbB-2, P53, P16 expression in primary breast pathology meaningful.2. CerbB-2 expression or P53, P16 expression prompted negative patients may have lymph node metastasis and poor prognosis.3. using ER, PR, CerbB-2 Joint detection is an important indicator of endocrine therapy guidance.4. CerbB-2-positive breast cancer suggest the degree of malignancy and poor prognosis.5. immunohistochemical method is simple, inexpensive features, can be used for clinical application of Herceptin with chemotherapy is the primary screening. FISH carried out to detect HER-2 gene as a complement IHC,IHC can avoid excessive false-positive patients receiving Herceptin treatment caused unnecessary financial burden and side effects of drug damage.
Keywords/Search Tags:Breast Cancer, CerbB-2, HER-2, IHC, FISH
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