Apoptotic activity in Libyan breast cancer.
ABSTRACT BACKGROUND: We evaluated the relationship of the apoptotic activity index (AI) and the standardized mitotic-apoptotic ratio (SMI/AI) with clinicopathological features and prognosis in Libyan female breast cancer (BC) patients. We then compared our results with corresponding results in Finnish and Nigerian female BC patients. METHODS: Histological samples of breast carcinoma from 130 patients were retrospectively studied: an estimation of the apoptotic activity per square millimeter (expressed as apoptotic activity index (AI)), and standardized mitotic-apoptotic ratio (SMI/AI) was made, and the results compared with the clinicopathological features and the patient's survival. RESULTS: There was a statistically significant correlation between the AI and most of the clinicopathological features; the strongest association was observed for clinical stage lymph node (LN) status (P = 0.005). There were also correlations between AI and histological grade (P = 0.035), large tumor size (P = 0.011) and the clinical stage (P = 0.009). There were, however, prominent AI differences between Libyan, Nigerian and Finnish populations. The mean values of AI and SMI/AI in Libyan BC patients were 12.8 apoptotic figures per square millimeter and 2.8, respectively. The Libyan AI is slightly higher than in Nigeria, but much higher than in Finland. The differences between countries are seen throughout the samples as well as being present in certain subgroups. The survival analysis indicated that short survival time was associated with high apoptotic indices values and so can identify aggressive tumors and provide significant prognostic support. The cutoff (4 and 18 apoptosis/mm2) of AI might be applied as a quantitative criterion for Libyan BC to separate the patients into good, moderate and bad prognosis groups. CONCLUSIONS: The results indicated that the differences in AI among the three countries may be due to the known variation in the distribution of genetic markers in these populations. Improvement in health care and introduction of screening programs, however, could be very helpful in the Libyan population.
Article: Quantitative comparison of apoptosis to cell proliferation and p53 protein in breast carcinomas.[show abstract] [hide abstract]
ABSTRACT: To clarify the correlation between apoptosis and tumor cell proliferative activity in human breast cancer and to investigate their relevance to p53 protein. Seventy-one breast carcinomas with histologic grading were analyzed, using counting of mitotic activity index (MAI) and apoptotic index (AI) to examine apoptosis and cellular proliferation, which were then compared with the expression of p53 protein by using a semiquantitative immunohistochemical method. Both the mean MAI and AI were significantly higher in the grade 3 groups (18.30 +/- 2.18 SE, 13.58 +/- 1.94) and 2 (11.32 +/- 1.30, 9.96 +/- 1.84) than in the grade 1 groups (8.24 +/- 1.10, 8.30 +/- 2.20) (P < .001). Also, MAI/AI was significantly highest in the grade 3 group (P < .001). A significant correlation was found between MAI and AI (r = .767, P < .01). Positive expression of p53 protein, indicated by distinct nuclear staining, was found in 35 of 71 carcinomas and was related to neither MAI nor AI (P > .05); there was no significant relation between p53-positive scoring and histologic grading (P > .05). Apoptosis in breast cancer seems to correlate with proliferative activity assessed by the mitotic index and supports the hypothesis that apoptosis may play a role in the selection of clonal subpopulations with high growth potential but is not regulated by the p53 system. Further research needs to be conducted to elucidate the relation between apoptosis and tumor progression and the significance of p53 in abnormalities in breast cancer.Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 02/1998; 20(1):1-6. · 0.41 Impact Factor
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ABSTRACT: We determined the mitotic and apoptotic index through the spectrum of pre-invasive ductal breast lesions to invasive carcinoma in search of disturbances in the proliferation/cell death balance in breast carcinogenesis. Seventy-two pure pre-invasive ductal breast lesions (without invasive carcinoma) and 103 invasive breast carcinomas were used. The numbers of mitotic and apoptotic cells were microscopically counted in hematoxylin and eosin stained sections (MI and AI, respectively), and the ratio of the values of MI and AI was calculated for each individual case (M/A index). A distinction was made between well differentiated and poorly differentiated breast lesions, based on histological type and nuclear grade, to arrive at two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 6-fold from DCIS to well differentiated invasive carcinoma. The AI remained in the same range, resulting in a 4-fold increase of the M/A index. For the poorly differentiated breast lesions, a significant increase in MI and AI was found from hyperplasia to poorly differentiated DCIS. From DCIS to poorly differentiated invasive carcinoma, the MI increased significantly and the AI decreased 2-fold (n.s.), resulting in a 2.5-fold significant increase of the M/A index. In conclusion, the net increase of the number of cells in the transition from well differentiated pre-invasive to well differentiated invasive carcinoma is accompanied by an increase of cell proliferation rather than decrease in apoptosis, suggesting that in these lesions, proliferation related mechanisms are most important in carcinogenesis and progression. In contrast, in poorly differentiated breast lesions, decreased apoptosis seems to be also important in carcinogenesis and progression. At present, we are gathering patients with invasive breast cancer who had a previous biopsy with a pre-invasive lesion to obtain further more direct evidence for this hypothesis.Breast Cancer Research and Treatment 12/1999; 58(2):163-9. · 4.43 Impact Factor
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ABSTRACT: Breast cancer is the most common cancer among American women, whereas Asian women, who consume a traditional diet high in soy products, have a relatively low incidence. Genistein is a prominent isoflavonoid in soy products and has been proposed as the agent responsible for lowering the rate of breast cancer in Asian women. We investigated the effects of genistein on cell growth and apoptosis-related gene expression in breast cancer cells MDA-MB-231. We found up-regulation of Bax and p21WAF1 expressions and down-regulation of Bcl-2 and p53 expression in genistein-treated cells. Furthermore, DNA ladder formation, CPP32 activation, and PARP cleavage were observed after treatment with genistein, indicating apoptotic cell deaths. Flow cytometry with 7-amino actinomycin D staining showed that the number of apoptotic cells increased with longer treatment of genistein. From these results, we conclude that genistein inhibits the growth of MDA-MB-231 breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through a p53-independent pathway. The up-regulation of Bax and p21WAF1 may be the molecular mechanisms by which genistein induces apoptosis, however, further definitive studies are needed. These results suggest that genistein may be a potentially effective chemopreventive or therapeutic agent against breast cancer.Oncogene 06/1999; 18(20):3166-72. · 6.37 Impact Factor