Melanie Louw

Gastric cancers of Western European and African patients show different patterns of genomic instability

BackgroundInfection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.MethodsDNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.ResultsTumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.ConclusionsGastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.

Microscopic diversity in oral Kaposi sarcoma

Kaposi sarcoma is the most common HIV-associated neoplasm, frequently presenting with oral mucosal involvement. This retrospective study aimed to assess and highlight the histomorphological spectrum of oral Kaposi sarcoma. A total of 135 cases diagnosed between 1990 and 2011 were retrieved from the archives of the Oral and Dental Hospital of the University of Pretoria, South Africa. Following histologic review, each case was placed into 1 of 7 categories based on the predominant pattern of growth. These histologic divisions included lesions designated as solid, lymphangioma-like, telangiectatic, desmoplastic, lymphangiectatic, ecchymotic, and anaplastic. The presence of coexistent pathology was identified in 25 cases, largely represented by superimposed candidiasis. Concomitant cytomegalovirus and non-necrotizing granulomatous inflammation were also observed. Although the prognostic significance of these variants is yet to be determined, the appreciation and recognition of such morphologic diversity remains essential in distinguishing these lesions from possible mimickers.

Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men.

Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis.

Immunotactoid glomerulonephritis in a child with HIV infection: a case report

Renal disease is a common complication of human immunodeficiency virus (HIV) infection in adults. In children, however, HIV pathology of the gastrointestinal and respiratory tracts predominates, whereas renal disease is often an incidental finding. In this report, we describe a child with stage III HIV infection associated with immunotactoid glomerulonephritis (IT). The patient was referred for investigation of idiopathic nephrotic syndrome. Electron microscopy of his renal biopsy specimen revealed numerous electron-dense microtubular deposits, arranged in parallel fashion, consistent with a diagnosis of IT. He received highly active antiretroviral therapy (HAART) as well as corticosteroids and is currently in remission. To our knowledge, this is the first report of IT in a child.

p16 and Ki-67 immunohistochemical staining reduces inter- and intra-observer variability in the grading of cervical squamous intraepithelial lesions of South African women

Background: Cervical carcinoma was the second leading malignancy in South African women (following breast carcinoma) in 2010. This study aimed to correlate histopathological criteria and immunohistochemical stains in terms of the grading of cervical intraepithelial precursor lesions and evaluate intra- and inter-observer variability with only histology and with additional immunohistochemical stains. Methods: Archival tissue from large-loop excision of the transformation zone (LLETZ) was graded on two separate occasions by an independent observer in terms of lesional severity. The section with the highest grade precursor lesion was selected and submitted for immunohistochemical stains that included p16 and Ki-67. These stains were also evaluated on two separate occasions by an independent observer. Results: This study showed kappa values of 0.47 and 0.46 respectively for the separate histological evaluations of the observer and the original pathology report. The kappa value for the two evaluations of the observer was 0.57. Thus inter- and intra-observer variability is fair with the use of routinely stained histological slides. The two Ki-67 assessments had a kappa value of 0.85 and the p16 had a value of 0.80. Intra-observer agreement was markedly higher when using immunohistochemistry. Conclusion: Although in most cases of precursor lesions of the cervix the grading can be made on routinely stained sections, intra- and inter-observer variability remains high. Immunohistochemical markers reduce this variability and aid in deciding in which group to place ambiguous lesions.

HPV types in cervical cancer tissue in South Africa: A head-to-head comparison by mRNA and DNA tests

Abstract Accurate identification of human papillomavirus (HPV)-types in cervical cancer tissue may be important for tailoring tests for primary screening and types to be included in a vaccine. The aim of this study was to compare test-performance of a 45-type HPV deoxyribonucleic acid (DNA)-test with a 9-type HPV messenger ribonucleic acid (mRNA)-test in cervical cancer tissues. In a case-series design 188 women with diagnosed cervical cancer during the period January 2008 to July 1, 2011 at the Gynaecological Oncology Unit, University of Pretoria, South Africa were recruited to the study. After cases with negative internal controls for DNA/mRNA detection (n = 18) and unconfirmed histology (n = 3) of cervical cancer were excluded, 167 women remained eligible for analysis. We compared 45 DNA-types detected through general primer (GP)5+/6+ polymerase chain reaction (PCR) and reverse line blot (RLB) genotyping with a modified version of the mRNA test PreTect HPV-Proofer detecting 9 genotypes (16, 18, 31, 33, 35, 45, 51, 52, 58). Histological types were 92.2% squamous cell carcinoma, 4.8% adenocarcinoma, and 3.0% adenosquamous carcinoma. Overall, HPV was detected in 95.2% (159/167) of specimens. The DNA- and mRNA tests each rendered 153/167 (91.6%) HPV positive results. When restricting the analysis to the 9 high-risk HPV-types included in the mRNA test, 91.6% (153/167) and 88.0% (147/167) were positive by the mRNA- and DNA-tests (P = .28), respectively. After hierarchical categorization of 9 comparable types, we found concordance in 66 of 67 specimens for HPV16, 25 of 27 specimens for HPV18, 19 of 21 specimens for HPV45, and only in 33 of 45 for HPV31, 33, 35, 51, 52, 58. The positivity rate for the HPV types 16, 18, and 45 and the positivity rate for HPV 16, 18, 45, 33 and 35 by both tests was 66% to 68% and 80% to 83%, respectively. Overall and when considering established high-risk types, the mRNA test has at least as high detection rate as the DNA test. The mRNA test can be an appropriate research tool to describe causative HPV-types in cervical cancer tissue for health care planning purposes.

HPV L1 capsid protein detection in high-risk human papillomavirus-positive cervical smears

Abstract Background: The L1 capsid protein is a viral nuclear protein that encapsidates the human papillomavirus (HPV) DNA to build new infectious particles. Previous studies in immune-competent patients have shown that detectable L1 protein in lowgrade squamous intraepithelial lesion (LSIL) smears is associated with remission in 60–75% of cases. Thus, the test can reduce interventions by approximately 75%. Objective: This study was performed to evaluate the use of HPV L1 capsid protein detection on cytology samples in a population with relatively high human immunodeficiency virus (HIV) prevalence and with known high-risk HPV (hrHPV) DNA results. Setting: Samples were obtained during a cervical cancer screening study at primary healthcare clinics in the Tshwane district, Gauteng. The HIV prevalence of the target group was estimated to be between 20% and 30%. Method: Conventional cervical cytology smears of 575 women were microscopically assessed and diagnosed. In addition, women were tested for the presence of HPV DNA on a cervical or vaginal sample. Immunocytochemical analysis was performed on morphologically abnormal smears and on a 52 control group smears reported to be negative for HPV DNA and morphological abnormalities. The detection of L1 capsid protein was carried out with the Cytoactiv® HPV L1 screening set, an antibody-based immunocytochemical stain. Results: A cytological diagnosis of LSIL was made in 19 women (3.3%), high-grade squamous intraepithelial lesions (HSILs) in 42 (7.5%) and malignancy in 1 (0.2%). Of the LSIL cases, 10 of 19 (52.6%) stained positive for the presence of the L1 protein, while only one of 42 HSIL (2.4%) cases stained positive. Three hundred and four cases (52.9%) tested positive for hrHPV DNA, including women with LSIL, HSIL and malignancy. All of the control cases stained negative for the L1 capsid protein. Conclusion: hrHPV was not a useful triage test for women with abnormal cellular morphology in this population. Promising results were reported for Cytoactiv® immunostaining as a triage test for patients with LSIL, but it added no value to samples known to be HPV-negative or reported to be morphologically negative. The immunostaining of smears reported to be HSIL or worse were almost universally negative, supporting the diagnostic accuracy of cytology and the expectation of persistence or progression of these lesions.