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The role of tissue inflammation in Kenyan women with breast cancer
Background The immune landscape of breast cancer (BC) molecular subtypes from Sub Saharan Africa is understudied and findings are mainly extrapolated from studies in Caucasians. The objective of this study was to describe the cellular and signalling milieu of BC tumour microenvironment and its assoc...
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| Format: | Thesis |
| Language: | English |
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Department of Pathology
2023
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| _version_ | 1867613204959461376 |
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| access_status_str | Open Access |
| author | Abdulrehman, Shahin Sayed |
| author2 | Govender, Dhirendra |
| author_browse | Abdulrehman, Shahin Sayed Govender, Dhirendra |
| author_facet | Govender, Dhirendra Abdulrehman, Shahin Sayed |
| author_sort | Abdulrehman, Shahin Sayed |
| collection | Thesis |
| description | Background The immune landscape of breast cancer (BC) molecular subtypes from Sub Saharan Africa is understudied and findings are mainly extrapolated from studies in Caucasians. The objective of this study was to describe the cellular and signalling milieu of BC tumour microenvironment and its associations with BCrisk factors, tumour characteristics and molecular subtypes in Kenyan women with breast cancer. Methods: Molecular subtyping of 838 cases of BC was performed based on Immunohistochemistry (Figure 1). Risk factor data and tumour characteristics were retrieved from an existing database. Visual quantification of overall Tumour Infiltrating Lymphocytes (TILs) was performed on Haematoxylin and Eosin-stained whole slide sections of 226 BC cases based on the guidelines of the International TIL working group. Tissue Microarrays (TMAs) of tumour were constructed, stained with immunohistochemistry for CD3, CD4, CD8, CD68, CD20 and Fox P3, scanned and analysed on the Leica Aperio platform. Cytokine profiles of ER positive and Triple Negative BC were performed using microarray gene arrays and results validated with the ELISA platform. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumour molecular subtypes. Linear and logistic regression models were used to assess the associations between risk factors and tumour features with TILs and TIL subtypes. Results: Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. Higher TILs were associated with high KI67, high grade and HER2 status, luminal B subtype, and smaller tumour size. The TILs were predominantly composed of CD3, CD8 and CD68 with a much smaller contribution of CD4 and CD20 and FOxP3. Differential expression of inflammatory related cytokines (GM-CSF, IL8, TGF β1 and MDC), at both the gene and the protein expression level were observed between Triple negative and ER positive BC. Conclusions: Our findings with regards to enrichment of TILs in more aggressive breast cancers are like what has been previously published, however the differential expression of inflammatory cytokines in breast cancer subtypes some of which has also been described in Caucasian and Asian populations warrants further studies as potential targets for therapeutic approaches and biomarkers of diagnosis and prognosis. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/36996 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:26.116Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Department of Pathology |
| publisherStr | Department of Pathology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/36996 The role of tissue inflammation in Kenyan women with breast cancer Abdulrehman, Shahin Sayed Govender, Dhirendra Naidoo, Richard Anatomical Pathology Background The immune landscape of breast cancer (BC) molecular subtypes from Sub Saharan Africa is understudied and findings are mainly extrapolated from studies in Caucasians. The objective of this study was to describe the cellular and signalling milieu of BC tumour microenvironment and its associations with BCrisk factors, tumour characteristics and molecular subtypes in Kenyan women with breast cancer. Methods: Molecular subtyping of 838 cases of BC was performed based on Immunohistochemistry (Figure 1). Risk factor data and tumour characteristics were retrieved from an existing database. Visual quantification of overall Tumour Infiltrating Lymphocytes (TILs) was performed on Haematoxylin and Eosin-stained whole slide sections of 226 BC cases based on the guidelines of the International TIL working group. Tissue Microarrays (TMAs) of tumour were constructed, stained with immunohistochemistry for CD3, CD4, CD8, CD68, CD20 and Fox P3, scanned and analysed on the Leica Aperio platform. Cytokine profiles of ER positive and Triple Negative BC were performed using microarray gene arrays and results validated with the ELISA platform. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumour molecular subtypes. Linear and logistic regression models were used to assess the associations between risk factors and tumour features with TILs and TIL subtypes. Results: Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. Higher TILs were associated with high KI67, high grade and HER2 status, luminal B subtype, and smaller tumour size. The TILs were predominantly composed of CD3, CD8 and CD68 with a much smaller contribution of CD4 and CD20 and FOxP3. Differential expression of inflammatory related cytokines (GM-CSF, IL8, TGF β1 and MDC), at both the gene and the protein expression level were observed between Triple negative and ER positive BC. Conclusions: Our findings with regards to enrichment of TILs in more aggressive breast cancers are like what has been previously published, however the differential expression of inflammatory cytokines in breast cancer subtypes some of which has also been described in Caucasian and Asian populations warrants further studies as potential targets for therapeutic approaches and biomarkers of diagnosis and prognosis. 2023-02-23T08:25:44Z 2023-02-23T08:25:44Z 2022 2023-02-20T12:08:40Z Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/36996 eng application/pdf Department of Pathology Faculty of Health Sciences |
| spellingShingle | Anatomical Pathology Abdulrehman, Shahin Sayed The role of tissue inflammation in Kenyan women with breast cancer |
| thesis_degree_str | Doctoral |
| title | The role of tissue inflammation in Kenyan women with breast cancer |
| title_full | The role of tissue inflammation in Kenyan women with breast cancer |
| title_fullStr | The role of tissue inflammation in Kenyan women with breast cancer |
| title_full_unstemmed | The role of tissue inflammation in Kenyan women with breast cancer |
| title_short | The role of tissue inflammation in Kenyan women with breast cancer |
| title_sort | role of tissue inflammation in kenyan women with breast cancer |
| topic | Anatomical Pathology |
| url | http://hdl.handle.net/11427/36996 |
| work_keys_str_mv | AT abdulrehmanshahinsayed theroleoftissueinflammationinkenyanwomenwithbreastcancer AT abdulrehmanshahinsayed roleoftissueinflammationinkenyanwomenwithbreastcancer |