Hodgkin Lymphoma at a Tertiary Cancer Center in Ethiopia: Novel Biomarkers and Characterization of the Tumor Microenvironment in Relation to Epstein Barr Virus (EBV)
| dc.contributor.advisor | Beyene Petros | |
| dc.contributor.author | Makka Adam | |
| dc.date.accessioned | 2025-08-17T23:40:33Z | |
| dc.date.available | 2025-08-17T23:40:33Z | |
| dc.date.issued | 2024-05 | |
| dc.description.abstract | Classificahon and idenhficahon of Hodgkin lymphoma (HL) relies on morphological and biomarker-based diagnosis. However, CD30 and CD15 used for the idenhficahon of HL, are not expressed on all tumor cells. This gap can be narrowed by combining detechon of the insulin-like growth factor II messenger RNA-binding protein 3 (IMP3). This study aimed to confirm the diagnoshc value of IMP3. In addition to investigating the prevalence of EBV among HL cases, the tissue cellular composition of EBV-related and EBV-unrelated cases also was assessed. Furthermore, the treatment outcomes and prognostic impact of FoxP3 and PD1 in the tumor microenvironment (TME) of classical HL (CHL) were determined. Clinical records of consecutive patients with HL diagnosed between the years 2014 and 2019 were reviewed. A tissue microarray (TMA) of 126 of CHL and nodular lymphocyte predominant HL from Tikur Anbessa Hospital was constructed. TMA sections were usedfor immunohistochemical staining and detection of Epstein Barr Virus encoded-RNA. The stained immune cells were quantified by HALO 2.3. A total of 91(68.4%) pahents were male and the male-to-female raho was 2.2:1 with a median age of 22 years. The majority of the cases, 67 (50%) were of the mixedcellularity and 40 (40%) of the nodular-sclerosis subtype. A total of 77 (61.1%) of HL cases expressed LMP1/EBER. The immunoreachvity of HL cases to IMP3 was determined and compared with the commonly used biomarkers for HL diagnosis. 122 (96.8%), 95 (75.4%), and 126 (100%) of the cases were posihve for CD30, CD15, and IMP3 markers, respechvely. Infiltration of CD8+, T-bet+, and FoxP3+ cells was higher in the TME of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, PD1 expression was higher in the TME of EBV-unrelated CHL (P < 0.001). In a Kaplan-Meir analysis, the 9-year overall survival (OS) and event free survival (EFS) was 78.6% and 66.5%, respectively. The patients in the high-risk group, International Prognostic Score (IPS ≥ 3), had inferior OS and EFS compared to the patients in the low-risk group (IPS< 3) (P= 0.04 for both survival outcomes). HIVassociated HL had inferior EFS (P= 0.016). Patients with low lymphocyte (≤ 0.6x109 cells/L) had inferior OS (HR= 10.9; 95% CI, 1.4-84; P= 0.016) and EFS (HR= 5.9; 95% CI, 1.7-20; P=0.005). Patients with high FoxP3+ cells (≥ 9%) and high PD1+ cells (≥ 24.6%) in the TME of CHL had poor prognosis. The 9-year OS for high FoxP3 was 64.6% with (HR= 4.3; 95% CI, 1.2-15.7; P= 0.02) and the 9-year OS for high PD1 was 57.1% with (HR=3.4; 95% CI, 1.2-15.7; P=0.03). Low lymphocyte count, high FoxP3+, and high PD1+ were all significantly associated with adverse overall survival in a multivariate Cox-regression. The present study supports previous reports that suggest the potenhal of using IMP3 as a diagnoshc biomarker for HL. The study findings further highlight the previously unrecognized possibility that distinct immunosuppressive mechanisms involving FoxP3+ and PDI-expressing cells may be in play within EBV-positive and negative HL types. Although the treatment outcomes is relahvely inferior compared to high-income countries, a significant proporhon of pahents with CHL, are cured when provided adequate treatment. Overall, HIV-associated CHL, low lymphocyte count, high FoxP3, and PD1 were associated with unfavorable treatment outcomes. | |
| dc.identifier.uri | https://etd.aau.edu.et/handle/123456789/6958 | |
| dc.language.iso | en_US | |
| dc.publisher | Addis Ababa University | |
| dc.subject | Histopathological Paqerns Of HL | |
| dc.subject | Insulin-Like Growth Factor II Messenger RNA Binding Protein 3 | |
| dc.subject | Epstein Barr Virus | |
| dc.subject | Tumor Microenvironment | |
| dc.subject | Treatment Outcome | |
| dc.subject | Foxp3 | |
| dc.subject | PD1 | |
| dc.subject | Prognosis | |
| dc.title | Hodgkin Lymphoma at a Tertiary Cancer Center in Ethiopia: Novel Biomarkers and Characterization of the Tumor Microenvironment in Relation to Epstein Barr Virus (EBV) | |
| dc.type | Thesis |