Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.
Background. Immunohistochemical assessment of breast cancer and stratification into the basic molecular subtypes afford a much deeper insight into the biology of breast cancer, while presenting with opportunities to exploit personalized, targeted treatment. Traditionally, the oestrogen, progesterone, and epidermal growth factor receptors are assessed. MUC1, a transmembrane mucin, has been demonstrated a potential prognostic and metastatic marker in breast cancer. However, there have been a limited number of studies addressing the predictive and prognostic features of MUC1 in African breast cancer. This study aims at addressing the expression profiles of MUC1 and other biomarkers in Ghanaian breast cancer and determines its predictive and prognostic characteristics, in relation to other clinicopathological features. Methods. Haematoxylin and eosin (H&E) slides of breast cancer cases were reviewed and 203 suitable cases were selected for tissue microarray (TMA) construction and immunohistochemistry. Anti-ER, PR, HER2, Ki-67, and MUC1 antibodies were used. Results from the immunostaining were analysed using SPSS version 23. Results. About 59% of cases expressed MUC1. Majority of cases in the study showed a lack of expression of all three traditional markers (29% expressed ER, 10.9% PR, and 20.7% HER2). Ki-67 index were 62.1% (low), 16.5% (moderate), and 21.4% (high). MUC1 expressions among the molecular classes were luminal A (60.7%), luminal B (68.8%), HER2 overexpression (87.5%), and triple negative (56.6%). There were significant associations between MUC1 and HER2 overexpression (p=0.01) and triple negative (p<0.01). Conclusion. The high proportion of breast cancer cases expressing MUC1, as well as its association with the two most aggressive molecular classes, indicate a substantial role in the biology of breast cancer in our cohort, and it is an indication of poor prognosis.
Background Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort. Method A 9-year retrospective cross-sectional study on archived tissue blocks–formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes. Results The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05). Conclusion The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.
Background: Histological diagnosis is crucial to the management of breast diseases. It determines the kind of disease, the treatment modalities, and the outcome of management. Our department receives breast biopsies from the northern sector of Ghana constituting over 50% of the Ghanaian population. This study aimed at elucidating the pattern of disease and associated traditional prognostic indices of breast cases in our department over a period of 9 years. Methods: Information on the demographic characteristics and the histological diagnoses made on all breast cases received and processed in the department were accessed and entered into an Excel spreadsheet. Slides were reviewed and IHC was done on suitable cases. Descriptive statistics were generated using IMB-SPSS version 23. Results: A total of 4276 breast cases were received by the department within the study period, with 97.6% being female. Age ranged (female/male) from 10 to 98/13 to 102 years, with mean ages of 38.2 years (SD ± 16.7) and 41.15 years (SD ± 21.6), respectively. Cases were evenly distributed in both left and right breasts and 4.3% were bilateral. Inflammatory conditions were seen in 7.5% of cases. The most diagnosed benign tumor was fibroadenoma (54%), followed by fibrocystic change (8.1%). Gynecomastia was diagnosed in 66.3% of males. Malignant cases were 38.6%, with invasive carcinoma NST being the most frequent (87.5%). Histological grades were I = 9.4%, II = 41.6%, and III = 49%. Molecular subtypes were luminal A (19.8%), luminal B (9.9%), Her2 (16%), and TNBC (54.3%). Conclusion:Our findings show an increase in breast cancer cases compared to previous studies in our center, suggesting increased awareness and improved diagnosis. However, this increase is consistent with most studies in sub-Saharan Africa.
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