Hadgu, Endale (2017) Molecular Characterization and Assessment of Viral Tumorigenesis in Breast Cancer among Women in Addis Ababa, Ethiopia. PhD thesis, Addis Ababa University.
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Abstract
In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. Estroge receptor (ER), Progesterone Receptor (PR), Ki-67 and Human Epidermal Growth factor (HER-2) receptor status were assessed using immunohistochemistry (IHC) from tissue microarrays (TMA). Fluorescence in situ hybridization (FISH) and Gene Protein Assay (GPA) was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases. Androgen Receptor (AR) was assessed using IHC from TMA and BRCA1 was assessed using IHC from whole section. EBV, HCMV and HPV viral proteins or/and DNA were assessed using IHC or/and multiplex qPCR. The 2013 St. Gallen international panel of expert’s recommendation for classification of breast carcinoma based on IHC was applied to molecularly classify the tumors. Information obtained also included age, tumor grade, histological type, and stage of disease. In this study, the most common molecular subtypes was Luminal A (40%) followed by Luminal B (26%), TNBC (23%) and HER2-enriched (10%). ER were positive in 65% of all tumors and 43% the participants were positive for PR. There was statistically significant variation in median age at diagnosis between the different molecular subtypes (P<0.05). There was a bimodal distribution of molecular subtypes in different age ranges at diagnosis with Luminal B subtype being more common at younger ages (median=36) and Luminal A subtype being more prevalent at older ages (median=42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer. AR was expressed in 80% of breast cancers, which is higher than the expression rates of both ER and PR. There was a statistically significant variation (P<0.05) in the proportion of AR positivity between ER-positive (93%) and ER-negative tumors (60%). There was a statistically significant variation (P<0.05) in the proportion of AR positive cases between PR-positive (98%) and PR-negative (70%) tumors as well. There was no statistically significant variation in the expression of AR between HER2-positive and HER2-negative tumors in this study (P=0.145). AR expression among TNBC was 48% which is significantly different (P<0.05) than the other molecular subtypes. No statistically significant correlation was found between the clinicopathological parameters and AR expression. There were loss/decreased BRCA-1 protein expression in 29% of all cases. No association was found between altered nuclear BRCA1 expression and ER expression. BRCA-1 expression was not associated with AR, HER2 and Ki67. There was no statistically significant difference in BRCA-1 expression among the molecular subtypes of breast cancer in this study. No association was found with age at diagnosis, tumor grade, clinical stage and histological type of tumor. Out of 113 participants 44 cases (39 %) had high Ki67 protein expression. High Ki67 was found to be significantly associated with median age (P<0.05). The median age at diagnosis for participants with high proliferation were 37 years compared to 42 years for participants with low proliferation. High tumor grade were associated high proliferation (P<0.05). We did find some association of Ki67 with ER; however, the association did not reach the level of statistical significance (P=0.074). There was also statistically significant variation (P<0.05) between the molecular phenotypes; Luminal B group had the highest proportion (83%) with high proliferation, followed by the TNBC (58%), then the HER2 enriched group (36%). All Luminal A subtypes had low Ki67. The concordance rate between the results of IHC and GPA for HER2 in all cases was 97.2%. The concordance rate of IHC and GPA was high in cases that were 3+ according to IHC (100%), but slightly lower in cases that were 2+ according to IHC (91.7%). There was no detection of HCMV and EBV in this study. 2 out of 82 (2.4%) samples were positive for HPVs. Out of the two cases positive for HPV one case had the high risk HPV16 genotype while the other were dual positive for the high risk HPV39 and low risk HPV6. Together, these studies make an important contribution to understanding the molecular characteristics of breast cancer and association of oncogenic viruses with breast cancer.
| Item Type: | Thesis (PhD) |
|---|---|
| Uncontrolled Keywords: | Breast cancer, Molecular subtypes, AR, BRCA1, Ki67, oncogenic viruses, Ethiopia, Africa |
| Subjects: | B Philosophy. Psychology. Religion > B Philosophy (General) R Medicine > R Medicine (General) |
| Divisions: | Africana |
| Depositing User: | Vincent Mpoza |
| Date Deposited: | 24 Oct 2018 08:35 |
| Last Modified: | 24 Oct 2018 08:35 |
| URI: | http://thesisbank.jhia.ac.ke/id/eprint/7053 |
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