Expression of p53, Glutathione S -Transferase- , and Bcl-2 Proteins and Benefit From Adjuvant Radiotherapy in Breast Cancer

التفاصيل البيبلوغرافية
العنوان: Expression of p53, Glutathione S -Transferase- , and Bcl-2 Proteins and Benefit From Adjuvant Radiotherapy in Breast Cancer
المؤلفون: E. Benini, Silvia Veneroni, Antonio Maucione, Monica Leutner, Umberto Veronesi, Roberto Zucali, A Luisi, Rado Kenda, Maria Grazia Daidone, Rosella Silvestrini
المصدر: JNCI Journal of the National Cancer Institute. 89:639-645
بيانات النشر: Oxford University Press (OUP), 1997.
سنة النشر: 1997
مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, Axillary lymph nodes, medicine.medical_treatment, Cellular detoxification, Mammary gland, Breast Neoplasms, Mastectomy, Segmental, Breast cancer, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Humans, Estrogen Receptor Status, Glutathione Transferase, Retrospective Studies, Chemotherapy, business.industry, Middle Aged, medicine.disease, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Isoenzymes, Radiation therapy, Treatment Outcome, medicine.anatomical_structure, Glutathione S-Transferase pi, Proto-Oncogene Proteins c-bcl-2, Cancer research, Hormonal therapy, Female, Radiotherapy, Adjuvant, Neoplasm Recurrence, Local, Tumor Suppressor Protein p53, business
الوصف: BACKGROUND In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer. PURPOSE The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990. METHODS The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered. RESULTS After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers. CONCLUSIONS Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.
تدمد: 1460-2105
0027-8874
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69b6372d16f1cf497279ec6ac8918eb5Test
https://doi.org/10.1093/jnci/89.9.639Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....69b6372d16f1cf497279ec6ac8918eb5
قاعدة البيانات: OpenAIRE