Histopathological characterization of lung tumours at the University Teaching Hospital, Lusaka, Zambia: a pilot study.

Background: There are limited data on histological classification of primary lung cancer from sub-Saharan Africa. Furthermore, the time trends of age-truncated incidence rates of lung cancer by histological phenotype in Zambia are also unknown. Objectives: The objective of this study was to determine histological types of lung tumours at the University Teaching Hospital (UTH) in Lusaka, Zambia. Methods: This was a retrospective pilot study of lung tumour biopsies collected from the histopathology laboratory at the UTH over a period of one year. Tissue sections were stained and when seen, lung cancer was classified using standard histological methods. Data were analysed using IBM SSPS version 23. Results: A total of 23 lung cancer tissues were retrieved. Histological types included eleven (47.8%) squamous cell carcinoma (SCC), six (26.1%) adenocarcinoma, two (8.7%) small cell carcinoma, two (8.7%) large cell carcinoma, 1 (4.3%) inflammatory myofibroblastic tumours and 1 (4.3%) pleural pulmonary blastoma. The results showed that the most affected age group was 60-69 years with most of the histological subtype in this age group being SCC. There was no statistically significant difference of histological subtypes across age groups, p=0.12. Conclusion: This study has shown that the most commonly diagnosed type of primary lung cancer is squamous cell carcinoma. More data are needed to further corroborate this observation.

High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs.

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we find that tumours that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment, and prognostic strategies.

Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia.

INTRODUCTION: Epstein-Barr virus (EBV) is a ubiquitous virus that infects more than 90% of the world's population, and is implicated in lymphoma pathogenesis. However, in Zambia during the diagnosis of these lymphomas, the association of the virus with the lymphomas is not established. Since most patients with lymphomas have poor prognosis, the identification of the virus within the lymphoma lesion will allow for more targeted therapy. The aim of this study was to provide evidence of the presence of the EBV in lymphomas diagnosed at the University Teaching Hospital (UTH) in Lusaka, Zambia. METHODS: One hundred and fifty archival formalin-fixed paraffin embedded suspected lymphoma tissues stored over a 4-year period in the Histopathology Laboratory at the UTH in Lusaka, Zambia, were analysed. Histological methods were used to identify the lymphomas, and the virus was detected using Polymerase Chain Reaction (PCR). Subtyping of the virus was achieved through DNA sequencing of the EBNA-2 region of the viral genome. Chi square or fisher's exact test was used to evaluate the association between EBV status, type of lymphoma and gender. RESULTS: The majority of the lymphomas identified were non-Hodgkin's lymphoma (NHL) (80%) followed by Hodgkin's lymphoma (HL) (20%). EBV was detected in 51.8% of the cases, 54.5% of which were associated with NHL cases, while 40.9% associated with HL cases. The predominant subtype of the virus in both types of lymphomas was subtype 1. One of the lymphoma cases harboured both subtype 1 and 2 of the virus. CONCLUSION: This study showed that EBV is closely associated with lymphomas. Therefore, providing evidence of the presence of the virus in lymphoma tissues will aid in targeted therapy. To our knowledge this is the first time such data has been generated in Zambia.

Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at the University Teaching Hospital, Lusaka, Zambia.

INTRODUCTION: Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its causative agent, Human Herpes virus 8 is not sought. This means poor prognosis for affected patients since the causative agent is not targeted during diagnosis and KS lesions may be mistaken for other reactive and neoplastic vascular proliferations when only histological techniques are used. Therefore, this study was aimed at providing evidence of Human Herpes virus 8 infection in Kaposi's sarcoma tissues at the University Teaching Hospital in Lusaka, Zambia. METHODS: One hundred and twenty suspected Kaposi's sarcoma archival formalin-fixed paraffin-wax embedded tissues stored from January 2013 to December 2014 in the Histopathology Laboratory at the University Teaching Hospital, Lusaka, Zambia were analysed using histology and Polymerase Chain Reaction targeting the ORF26 gene of Human Herpes virus 8. RESULTS: The predominant histological type of Kaposi's sarcoma detected was the Nodular type (60.7%) followed by the plaque type (22.6%) and patch type (16.7%). The nodular lesion was identified mostly in males (40.5%, 34/84) than females (20.2%, 17/84) (p=0.041). Human Herpes virus 8 DNA was detected in 53.6% (45/84) and mostly in the nodular KS lesions (60%, 27/84) (p=0.035). CONCLUSION: The findings in this study show that the Human Herpes virus-8 is detectable in Kaposi's sarcoma tissues, and, as previously reported in other settings, is closely associated with Kaposi's sarcoma. The study has provided important baseline data for use in the diagnosis of this disease and the identification of the virus in the tissues will aid in targeted therapy.