Anatomical Pathology

Permanent URI for this community

https://scholar.sun.ac.za/handle/10019.1/169

Browse

Browsing Anatomical Pathology by browse.metadata.advisor "Fernandez, Pedro"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Hepatitis b virus-related hepatocellular carcinoma in south africa: investigations into the risk profile of a previously unscreened population from the Western Cape
    (Stellenbosch : Stellenbosch University, 2018-12) Chotun, Bibi Nafiisah; Anderson, Monique Ingrid; Preiser, Wolfgang; Fernandez, Pedro; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.
    ENGLISH ABSTRACT: Hepatocellular carcinoma (HCC) is a neglected major public health problem worldwide. In SubSaharan Africa (SSA), most HCC cases are diagnosed with advanced disease, well past the timing of possible treatment. Most HCC cases worldwide are caused by chronic infection with hepatitis B virus (HBV). Although the bulk of the burden of HBV is in SSA, there are no screening programmes implemented in the general African population so only 0.8% of HBV-infected individuals are diagnosed. Most research on HBV-related HCC has been conducted in Asia, where HBV is also endemic, but where there are differences in disease progression and presentation. The present study investigated HBV and HCC from an African perspective and tackled these public health issues by incorporating three key components for early diagnosis of HBV-related HCC: HBV screening, HCC biomarkers, and HBV-related HCC genomics. The HBV screening study found the prevalence of HBV in a South African community-based cohort using a validated point-of-care test to be 2.2% (95% CI: 1.4%–3.3%). The test performed well in the field and had a sensitivity, specificity, negative and positive predictive values of 100%. The test was also accepted by the community (93% uptake) and health care providers. The results of the present study support the case for the implementation of HBV screening in South Africa by demonstrating the magnitude of the HBV health problem in South Africa and new evidence that the POCT test performs well in the field, is accepted by the community and health care providers, and that patients diagnosed with the test can be successfully linked to treatment and long-term follow-up. The HCC biomarker study found significant differences in methylation expression levels in CpG islands in the promoter region of the tumour suppressor gene RASSF1A between HCC cases and normal liver tissue controls as well as a significant association between HBV genotype A and HCC. Although the sample size was small, it showed that there are biomarkers that may be used to identify HCC, paving the way for future studies looking into developing HCC risk scores for early diagnosis of HCC. Using whole-exome sequencing, the HBV-related HCC genomics study identified two novel germline variants in the SMARCA1 and RAB19 genes that in the absence of other risk factors besides HBV infection, could have contributed to early-onset HBV-related HCC in their respective hosts. Overall, these data provide evidence that early diagnosis of HBV-related HCC in an African setting is possible especially if a multi-targeted approach is taken. The simplest approach to minimise the incidence of HCC in SSA would be to implement HBV screening, at the very least in pregnant women, to break the transmission cycle of HBV. Moreover, the biomarkers of interest identified in the present study should be investigated further in larger cohorts and non-invasive patient samples to determine their utility in stratifying HCC risk. Lastly, the WES study showed that there are germline variants that could predispose carriers to HCC although these results need to be further investigated in in-silico and proteomic studies.
  • Thumbnail Image
    Item
    Prevalence of ERG overexpression in prostate cancer on prostate biopsies at a tertiary public hospital in the Western Cape, South Africa
    (Stellenbosch : Stellenbosch University, 2023-12) McCree, Kevin; Van Wyk, Abrie; Fernandez, Pedro; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Division of Anatomical Pathology.
    ENGLISH ABSTRACT: Background: Prostate cancer is the most diagnosed non-cutaneous malignancy in men in South Africa across all race groups with 10495 new cases reported in 2019. The TMPRSS2-ERG fusion gene and resultant overexpression of ERG is estimated to occur at a rate of 30-50% within prostate cancer. The fusion gene is specific to prostate cancer and high grade prostatic intraepithelial neoplasia and has not been reported in other malignant neoplasms. The TMPRSS2-ERG fusion gene, and by implication the overexpression of ERG, may serve as a diagnostic, prognostic or therapeutic biomarker. The prevalence of the TMPRSS2-ERG fusion gene in prostate carcinoma in South Africa has not been investigated previously. We sought to determine the prevalence of the TMPRSS2-ERG gene fusion among men undergoing prostate biopsies at Tygerberg Hospital, Cape Town, South Africa and to determine whether there is an association between prostate cancer grade and ethnicity/race. Methods: This is a retrospective descriptive laboratory study where we analysed 362 prostate biopsies, diagnosed with prostate cancer, between January 2010 and December 2017. All 362 cases were reviewed, and the diagnosis was confirmed. 336 cases were stained with ERG (Cell Marque, clone EP111) an adequate surrogate marker for the TMPRSS2-ERG fusion gene. The prevalence was calculated and compared with Gleason grade group and ethnicity/race to determine if there is an association. Results: ERG overexpression was detected in 34% of cases. Our study showed an association with a lower Gleason score and ERG overexpression. There is a higher prevalence of TMPRSS2-ERG amongst the coloured population in this cohort, at 34%. Conclusions: This is the first study to characterise the prevalence of ERG overexpression in prostate cancer in patients who underwent prostate biopsies in South Africa. Our results show that this gene rearrangement is common in the study population and that the prevalence of 34% is within the range reported in international literature.