Prognostic Values of Gene Copy Number Alterations in Prostate Cancer.

Whilst risk prediction for individual prostate cancer (PCa) cases is of a high priority, the current risk stratification indices for PCa management have severe limitations. This study aimed to identify gene copy number alterations (CNAs) with prognostic values and to determine if any combination of gene CNAs could have risk stratification potentials. Clinical and genomic data of 500 PCa cases from the Cancer Genome Atlas stable were retrieved from the Genomic Data Commons and cBioPortal databases. The CNA statuses of a total of 52 genetic markers, including 21 novel markers and 31 previously identified potential prognostic markers, were tested for prognostic significance. The CNA statuses of a total of 51/52 genetic markers were significantly associated with advanced disease at an odds ratio threshold of ≥1.5 or ≤0.667. Moreover, a Kaplan-Meier test identified 27/52 marker CNAs which correlated with disease progression. A Cox Regression analysis showed that the amplification of MIR602 and deletions of MIR602, ZNF267, MROH1, PARP8, and HCN1 correlated with a progression-free survival independent of the disease stage and Gleason prognostic group grade. Furthermore, a binary logistic regression analysis identified twenty-two panels of markers with risk stratification potentials. The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa.

Chromosome-specific segment size alterations are determinants of prognosis in prostate cancer.

Currently, risk stratification is the most difficult problem in prostate cancer (PCa) management. Gleason grading cannot adequately predict cancer progression. This study aimed to identify chromosome-specific segment size alterations that could aid risk stratification and predict metastasis using a retrospective cohort-study strategy. A binary logistic regression model was generated using 16 chromosome-specific segments with size alterations (deletions and amplifications) that showed associations with disease stage (primary versus metastatic). The regression model was trained with the MSKCC PIK3R1 PCa cohort (n = 1417), and validated with the TCGA Firehose Legacy (n = 500), MSKCC Prostate Oncogenome Project (n = 218), and the SU2C/PCF Dream Team (n = 150) PCa cohorts. Furthermore, the capacity of the model to predict metastasis between primary tumours with metastasis (n = 54) and primary tumours without metastasis (n = 54) was tested. The accuracy, sensitivity, and specificity of the model at disease stage stratification ranged from 69.02% to 88.55%, 72.8% to 86.00% and 66.30% to 89.50%, respectively. The model also showed good performance at metastasis prediction with accuracy, sensitivity, and specificity of 57.41%, 62.96% and 51.85%, respectively. The study conclusion was that chromosome-specific segment size alterations can aid risk stratification and metastasis prediction. The significance of the study findings is that in combinations with clinical, biochemical, and histopathological variables, chromosome-specific alterations could improve current risk stratification and prediction models for PCa.

Clinicopathological pattern of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 over-expression of epithelial ovarian carcinomas in Nigeria.

Background: Ovarian cancer is the leading cause of death from all gynaecological malignancies. Only few biomarkers of epithelial ovarian cancer (EOC) prognosis have been studied so far among Nigerian patients. Objective: To determine the pattern of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression in patients with EOC seen in Nigeria. Materials and Methods: This was a retrospective multicentre study of 102 cases of epithelial ovarian cancers. Relevant clinical information was obtained from hospital-based records in the 3 participating centres. Tissue microarrays were constructed using representative tumour tissue and the ER, PR and HER2 immunohistochemical staining was carried out at the University of Chicago, United States of America. Results: Serous carcinomas predominated (71% of cases). ER positivity was observed in 31.4%, PR positivity in 21.5% and HER2/neu in 16.7% of tumours. Fifty-two percent of tumours were triple negative. Serous tumours were significantly associated with ER positivity (p=0.001). Mean patient age for EOC was 52.6 ± 13.1 years. There were no statistically significant associations between hormone receptor status and histological grade, FIGO staging or survival. Conclusion: Serous tumours were significantly associated with ER expression while non-serous tumours tended to be triple negative.

Prevalence and predictors of squamous intraepithelial lesions in human immunodeficiency virus positive women in Sagamu, southwest Nigeria.

Background: Cervical cancer is still a public health problem in many developing countries, like Nigeria. HIV infection makes HPV infections last longer, progress to squamous intraepithelial lesion of the cervix, and eventually lead to invasive cervical cancer. Objective: Find out how often squamous intraepithelial lesions (SIL) happen and what causes them in HIV-positive women in Sagamu, southwest Nigeria. Methods: A cross-sectional study was done with 165 women with HIV and 165 women without HIV. Pap smears were done on all of the people in the study. The data was looked at with IBM-SPSS Windows v. 23. Results: Both groups were about the same age and had the same number of children (P=0.194 and P=0.388, respectively). The participants' average age (SD) was 36.8 (5.6), and the median number of children they had was 3. HIV-positive women were much more likely to have an abnormal cytology smear (24.8%) than HIV-negative women (7.3%) (2 = 18.904, P 0.001). There wasn't a link between having HIV and the severity of cervical lesions (2 = 3.66, P = 0.162). A CD4 cell count of less than 350 cells/mm3was found to be a strong predictor of an abnormal cervical cytological smear in HIV-positive women (AOR: 25.5; CI: 8.8-73.5; P 0.001). Conclusion: In Sagamu, Nigeria, the number of HIV-positive women with SIL of the cervix was much higher than the number of HIVnegative women with SIL of the cervix. HIV-positive women, especially those with a low number of CD4 cells, need cervical smear tests more often. This will make sure that pre-invasive lesions are found and treated as soon as possible.

Semantic annotation for computational pathology: multidisciplinary experience and best practice recommendations.

Recent advances in whole-slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence-based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilise information embedded in pathology WSIs beyond what can be obtained through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue, and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms that are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts, and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary, and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project.

MSI-WES: a simple approach for microsatellite instability testing using whole exome sequencing.

Aim: To demonstrate that MSI-WES is an accurate testing method for microsatellite instability (MSI). Materials & methods: Microsatellite-based indels were counted in the variant call-formatted whole exome sequencing (WES) data of 441 gastric cancer cases using Unix-based algorithms, and the counts expressed as a fraction of the genome sequenced to obtain next-generation sequencing-based MSI indices. Results: The next-generation sequencing-based MSI indices showed a near-perfect concordance with PCR-based MSI status, and moderate to good correlations with the molecular targets of MSI index, MLH1 expression and MLH1 methylation status, at a level comparable to the strengths of correlation between PCR-based MSI status and molecular targets of MSI index/MLH1 expression and methylation. Conclusion: MSI-WES is a valid, adequate and sensitive approach for testing MSI in cancer.

Targeted next generation sequencing reveals a common genetic pathway for colorectal cancers with chromosomal instability and those with microsatellite and chromosome stability.

INTRODUCTION: Microsatellite stable sporadic colorectal cancers (CRCs) can be classified as either tumours with chromosomal instability (CIN+) or tumours that are 'Microsatellite and Chromosomal Stable' (MACS). The CIN + tumours are aneuploid whilst MACS are near-diploid; little else is known about their differences. We compared the mutation profiles of CIN + and MACS CRCs. METHOD: Targeted Next Generation Sequencing for mutation in 26 driver genes (TruSight-26 kit) was undertaken in 46 CIN + and 35 MACSCRCs. Tumours were compared for mutation frequency, allelic imbalance and clonal heterogeneity. RESULTS: Mutations were detected in 58% genes and, overall, mutation in driver genes was at expected frequencies. Comparison of classes revealed similar mutation frequencies in most genes and allelic imbalance atAPC and TP53. Differences were seen in mutation frequency in KRAS (41% CIN+ vs 68% MACS, p = 0.015) and GNAS (0% CIN+ vs 12% MACS, p = 0.032). Twenty percent CIN + CRCs harboured mutations only in TP53 - a profile not seen in the MACS tumours (p = 0.009). None of the differences were significant after multiple testing corrections. CONCLUSIONS: The mutation profiles of CIN and MACS CRCs are similar. The events allowing aneuploidy (or forcing retention of diploidy) remain unknown.

Targeted Next-Generation Sequencing Validates the Use of Diagnostic Biopsies as a Suitable Alternative to Resection Material for Mutation Screening in Colorectal Cancer.

BACKGROUND: Mutation testing in the context of neoadjuvant therapy must be performed on biopsy samples. Given the issue of tumour heterogeneity, this raises the question of whether the biopsies are representative of the whole tumour. Here we have compared the mutation profiles of colorectal biopsies with their matched resection specimens. METHODS: We performed next-generation sequencing (NGS) analysis on 25 paired formalin-fixed, paraffin-embedded colorectal cancer biopsy and primary resection samples. DNA was extracted and analysed using the TruSight tumour kit, allowing the interrogation of 26 cancer driver genes. Samples were run on an Illumina MiSeq. Mutations were validated using quick-multiplex-consensus (QMC)-polymerase chain reaction (PCR) in conjunction with high resolution melting (HRM). The paired biopsy and resection tumour samples were assessed for presence or absence of mutations, mutant allele frequency ratios, and allelic imbalance status. RESULTS: A total of 81 mutations were detected, in ten of the 26 genes in the TruSight kit. Two of the 25 paired cases were wild-type across all genes. The mutational profiles, allelic imbalance status, and mutant allele frequency ratios of the paired biopsy and resection samples were highly concordant (88.75-98.85%), with all but three (3.7%) of the mutations identified in the resection specimens also being present in the biopsy specimens. All 81 mutations were confirmed by QMC-PCR and HRM analysis, although four low-level mutations required a co-amplification at lower denaturation temperature (COLD)-PCR protocol to enrich for the mutant alleles. CONCLUSIONS: Diagnostic biopsies are adequate and reliable materials for molecular testing by NGS. The use of biopsies for molecular screening will enhance targeted neoadjuvant therapy.

Blood cellular markers of inflammation in Breast Cancer and response to Neoadjuvant Chemotherapy

Background:Breast cancer is the most common female malignancy in Nigeria. Neoadjuvant chemotherapy is the first line treatment for locally advanced breast cancer. The advancement of many cancers is accompanied by inflammation, and inflammatory cells play an essential role in the progression.Objective:To determine if haematological parameters can predict the responsiveness of breast cancer to neoadjuvant chemotherapy regime.Method:A prospective cohort study of all breast cancer patients who had neoadjuvant chemotherapy betweenJuly 2017 andDecember 2018was carried out. Haematological parameters of red cell count (RCC), white cell count(WCC), neutrophil count (NC), lymphocyte count (LC), platelet count (PC), red cell distribution width (RCDW), mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were measured. Response to chemotherapy was assessed by measuring the longest diameter of the lump and largest lymph node and applying the UICC criteria.Results: Thirty-five females with breast cancer with the age range of 33-82 years and mean age of 48± 11yearswere studied. The overall clinical response rate was 80% consisting of 40% complete clinical response, 40% partial clinical response, 8.6% stable disease and 11.4% progressive disease. Eleven (78.6%) with PLR values below average had good clinical response while 21.4% of those with PLR value above average had a good clinical response(χ2= 8.4, p =0.006)Conclusion: The study showed that PLR is associated with complete clinical response to neoadjuvant chemotherapy and should be used as part of routine assessment before chemotherapy

Prevalence, Predictive Factors, and Characteristics of Osteoporosis in Hyperthyroid Patients.

OBJECTIVE: The osteoporosis in thyroid disorder has the lowest report especially in sub-Saharan Africa. This study aims to determine the prevalence, predictive factors, and characteristics of osteoporosis in hyperthyroid patients. METHOD: Forty (40) hyperthyroid patients and healthy controls ages 21-50 years were recruited in this study. Questionnaires were administered to capture bio- and clinical data. Biochemical tests included blood, thyroid functions, intact parathyroid hormone, corrected calcium, and 25-hydroxyvitamin D tests. Bone mineral density (BMD) was also evaluated. Data were analyzed using the SPSS 21. A p value < 0.05 was regarded as significant. RESULTS: Osteoporosis was observed in 18 (45%) of study subjects, 13 (72.2%) females and 5 (27.8%) males, respectively. The BMD of the hyperthyroid patients had a negative correlation with free triiodothyronine, FT3 (r = -0.49, p = 0.005), FT4 (r = -0.33, p = 0.009), corrected calcium (r = -0.31, p = 0.039), alkaline phosphatase (r = -0.53, p < 0.001), and osteocalcin (r = -0.61, p < 0.001). Conversely, a positive association with thyroid-stimulating hormone (TSH) (r = 0.54, p < 0.001) was observed. Multiple regression showed osteocalcin (p < 0.001) and TSH (p = 0.015) as independent predictors of osteoporosis. CONCLUSION: Thyrotoxicosis is a risk factor for osteoporosis occurrence, and we recommend routine screening for this bone disease in persons over 20 years old with this disorder.

N_LyST: a simple and rapid screening test for Lynch syndrome.

AIMS: We sought to use PCR followed by high-resolution melting analysis to develop a single closed-tube screening panel to screen for Lynch syndrome. This comprises tests for microsatellite instability (MSI), MLH1 methylation promoter and BRAF mutation. METHODS: For MSI testing, five mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1) were developed. In addition, primers were designed to interrogate Region C of the MLH1 promoter for methylation (using bisulphite-modified DNA) and to test for mutations in codon 600 of BRAF. Two separate cohorts from Nottingham (n=99, 46 with MSI, 53 being microsatellite stable (MSS)) and Edinburgh (n=88, 45 MSI, 43 MSS) were tested. RESULTS: All the cases (n=187) were blind tested for MSI and all were correctly characterised by our panel. The MLH1 promoter and BRAF were tested only in the Nottingham cohort. Successful blinded analysis was performed on the MLH1 promoter in 97 cases. All MSS cases showed a pattern of non-methylation while 41/44 cases with MSI showed full methylation. The three cases with MSI and a non-methylated pattern had aberrations in MSH2 and MSH6 expression. BRAF mutation was detected in 61% of MSI cases and 11% of MSS cases.Finally, 12 cases were blind screened by using the whole panel as a single test. Of these, five were identified as MSS, four as MSI/non-LS and three as MSI/possible LS. These results were concordant with the previous data. CONCLUSION: We describe the Nottingham Lynch Syndrome Test (N_LyST). This is a quick, simple and cheap method for screening for Lynch syndrome.

Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.

BACKGROUND: Checkpoint kinase 1 (CHEK1), a DNA damage sensor and cell death pathway stimulator, is regarded as an oncogene in tumours, where its activities are considered essential for tumourigenesis and the survival of cancer cells treated with chemotherapy and radiotherapy. In breast cancer, CHEK1 expression has been associated with an aggressive tumour phenotype, the triple-negative breast cancer subtype, an aberrant response to tamoxifen, and poor prognosis. However, the relevance of CHEK1 expression has, hitherto, not been investigated in an indigenous African population. We therefore aimed to investigate the clinicopathological, biological, and prognostic significance of CHEK1 expression in a cohort of Nigerian breast cancer cases. MATERIAL AND METHODS: Tissue microarrays of 207 Nigerian breast cancer cases were tested for CHEK1 expression using immunohistochemistry. The clinicopathological, molecular, and prognostic characteristics of CHEK1-positive tumours were determined using the Chi-squared test and Kaplan-Meier and Cox regression analyses in SPSS Version 16. RESULTS: Nuclear expression of CHEK1 was present in 61% of breast tumours and was associated with tumour size, triple-negative cancer, basal-like phenotype, the epithelial-mesenchymal transition, p53 over-expression, DNA homologous repair pathway dysfunction, and poor prognosis. CONCLUSIONS: The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

"Squirrel" Primer-Based PCR Assay for Direct and Targeted Sanger Sequencing of Short Genomic Segments.

Currently, short DNA segments of sub-100 bp can be sequenced either directly by next-generation sequencing and pyrosequencing, which are expensive, or indirectly, via Sanger sequencing combined with the cumbersome and failure-prone plasmid cloning. To circumvent these issues, we have generated a novel sequencing-purposed PCR assay using long-tailed primers (squirrel primers) to Sanger sequence directly sub-100 bp genomic amplicons. Squirrel primers, 40-65 nt in length, were used to amplify 51-93 bp long genomic sequences of KRAS exons 2 and 3, BRAF exon 15, PI3K catalytic subunit alpha exon 20, and phosphatase and tensin homolog exon 3 from colorectal cancer (CRC) cell lines and preamplified clinical CRC samples with known mutation status by PCR. Following this, a short second pair of primers that bind at the 5' region of the long tails was used for sequencing on the 3130 × l ABI Prism Genetic Analyzer. The sequencing data were analyzed via FinchTV software. High-quality sequencing data were obtained from 51 to 93 bp long genomic sequences with our novel PCR assay, with capture of all of the target sequences in all of the samples in both the forward and reverse directions and confirmation of the mutation status of the CRC samples. Whereas the sequencing quality was independent of the template type, it showed a squirrel primer tail length-dependent pattern. Our novel PCR assay for direct and targeted Sanger sequencing of short genomic segments has potential applications in focused molecular/genetic profiling of cancer in research and diagnostics fields in which fragmented DNA, such as circulating tumor DNA and archival tissue DNA, are used as starting templates.

A refined method to study gene dosage changes in vitro using CRISPR/Cas9.

AIMS: Gene dosage can have a major impact on cell biology, although, hitherto, it has been difficult to study using in vitro models. We sought to refine and accelerate the development of 'gene dosage' models through using CRISPR/Cas9 (a gene editing technology) for sequential knockout of gene alleles. METHODS: Our method involved (1) using Cas9 nuclease mRNA rather than expression plasmids, (2) using a fluorescently labelled FAM-6 tracr complexed with guide RNA and (3) using high-resolution melting (HRM) analysis to screen for mutations. HCT116 cells, wild-type for TP53, were transfected with different molarities of FAM-6 tracr-labelled and guide RNA targeting different exons of TP53 and selected by fluorescence-activated cell sorting. Single-cell colonies were then isolated, expanded and tested for mutation in the targeted region by PCR/HRM. RESULTS: Out of 32 clones tested, 12 have shown aberrant melting by HRM, giving a targeting efficiency of 37.5%. One clone was sequenced and a heterozygous mutation found - in this case comprising a single base deletion in exon 3. mRNA sequencing confirmed the mutation was expressed, and western blotting for p53 showed the presence of both wild-type and truncated protein bands. Changes in expression of MDM-2 isoforms suggested a functional effect of the induced TP53 mutation. CONCLUSIONS: We have developed an in vitro model to study TP53 gene dosage effects. The protocol is efficient and applicable to any gene. Importantly, we have used Cas9 mRNA and labelled tracr/guide RNA to isolate likely mutated cells and HRM for rapid mutation detection.

QMC-PCRx: a novel method for rapid mutation detection.

AIMS: We previously described the quick multiplex consensus PCR (QMC-PCR) as a method for rapid mutation screening in low-quality template. QMC-PCR has two-stages: a prediagnostic multiplex (PDM) reaction followed by a single specific diagnostic reaction with high-resolution melting (HRM) analysis. We aimed to develop QMC-PCRx in which second stage was multiplexed to allow testing of multiple targets. METHODS: The PDM reaction was retained without change. For the second stage, in silico design was used to identify targets amenable to a multiplex specific diagnostic reaction and multiplex HRM (mHRM) analysis. Following optimisation, 17 colorectal cancers were tested for mutation in five hotspots. For QMC-PCR, each target was tested individually. For QMC-PCRx, the targets were tested in the following combinations (i) KRAS exon 3/PIK3CA exon 20/PTEN exon 3 in triplex and (ii) PTEN exon 7/NRAS exon 2 in duplex. The degree of agreement between the novel QMC-PCRx and the standard QMC-PCR was tested by the percentage concordance. RESULTS: Optimisation of mHRM showed that peaks needed to be separated (without overlap) and the optimal number was three targets per test. Our experimental design produced distinct and widely separated peaks for the individual targets although one of the primers needed a GC-tail. A total of 85 individual targets were tested; this required 85 second-stage PCR/HRM tests by QMC-PCR versus 34 second-stage tests by QMC-PCRx. The percentage concordance between the singleplex and multiplex methodologies was 100%. CONCLUSIONS: A multiplexed analysis using HRM is possible without loss of diagnostic accuracy. The novel QMC-PCRx protocol can significantly reduce workload and costs of mutation screening.

Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications.

Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management. This study investigated the biological, clinicopathological and prognostic significance of Ku 70/80 expression in a BC cohort from a Nigerian population. Ku 70/80 expression was determined in 188 well-characterized formalin-fixed, paraffin-embedded (FFPE) BC samples using tissue microarray and immunohistochemistry. Ku 70/80 expression was correlated with clinicopathological, molecular and prognostic characteristics of patients. Ku 70/80 was expressed in 113 (60.1%) tumors, and was positively associated with metastatic disease, triple-negative and basal phenotype, BRCA1 down regulators (MTA-1 and ID4), p-cadherin, PI3KCA and p53 expression. It inversely correlated with BRCA1, BRCA2, BARD1 and p27. Ku 70/80 was predictive of breast cancer-specific survival in multivariate analysis, but not of disease-free interval. This study demonstrated that Ku 70/80 expression is associated with triple negativity and down-regulation of the homologous recombination pathway of DNA repair. Therefore, the development of novel drugs to target KU70/80 may improve the patients' outcome in the treatment of Black BC.

Spectrum and prevalence of thyroid diseases seen at a tertiary health facility in Sagamu, South-West Nigeria.

BACKGROUND: The prevalence of goitrous swelling has reduced in Nigeria since the introduction of salt iodisation programme. Thyroid disorders are the second most common endocrine disorder after diabetes mellitus worldwide. They present to general outpatient, medical and surgical clinics accompanied by great anxiety and poor health-related quality of life. OBJECTIVES: The study aimed to determine and describe the spectrum of thyroid disorders seen at Olabisi Onabanjo University Teaching Hospital over a 10-year period. MATERIALS AND METHODS: This was a retrospective analysis of records of patients who presented to the hospital with thyroid swellings over a 10-year period (June 2004 to June 2014). Clinicopathological and demographic data obtained from hospital records in 175 patients diagnosed by clinical examination, thyroid ultrasound, hormone profile and histological confirmation in cases that had surgery were analysed for this study. RESULTS: The records of 175 patients were obtained comprising 151 (86.3%) females and 24 (13.7%) males (female to male ratio of 6.3:1) with age range from 18 to 76 years and mean age of 42.3 years, standard deviation 13.5. With clinical diagnosis, distribution of thyroid diseases was simple goitre 103 (58.9%), toxic goitre 64 (36.6%), hypothyroidism 3 (1.7%), malignant goitre 4 (2.3%) and thyroiditis 1 (0.6%). The age group of 30-49 years had the highest prevalence of the thyroid diseases 100 (57.2%) while the extremes of age, below 20 and over 70 years had the least (5.1 and 2.9%, respectively). CONCLUSION: The prevalent form of thyroid diseases seen at Olabisi Onabanjo University Teaching Hospital was simple goitre and most common in females. Studies on autoimmunity and other goitrogens are required to further elucidate the cause of this high prevalence.

Cancer mutation screening: Comparison of high-resolution melt analysis between two platforms.

High-resolution melt analysis (HRMA) is a cheap and reliable post-polymerase chain reaction (PCR) cancer mutation screening technique, which is fast gaining clinical relevance. The HRMA capabilities of the LightScanner (Idaho Technology) have been severally studied. However, the ABI 7500 HRM has not been tested against the purpose-built HRM instrument such as the LightScanner. DNA from formalin-fixed, paraffin-embedded gastric cancer, colorectal cancer, and normal tissue as well as from colorectal cancer cell lines were amplified at exons 2, 3, and 4 of KRAS, and at exons 11 and 15 of BRAF in the ABI 7500 fast real-time PCR machine and subjected to melting both on the ABI and on the LightScanner. HRMA data were analysed with the ABI HRM software v2.0.1 and the LightScanner Call-IT 2.5. We tested the ABI 7500 HRM for internal precision, accuracy, sensitivity, and specificity at mutation screening relative to the LightScanner, using crude percentage concordance, kappa statistics, and the area under the receiver operator characteristics (AUROC) curve on SPSS version 19. The results show that the ABI 7500 HRMA has a high internal precision, and excellent concordance, sensitivity, and specificity at mutation screening compared with the LightScanner. However, in contrast to the LightScanner HRM software analysis, the ABI HRM software v.2.0.1, cannot distinguish real from certain pseudovariations in PCR amplicons that are sometimes brought about by the artefacts of the melting process. In conclusion, the ABI HRM has a comparable performance level with the LightScanner, although in certain respects mentioned previously, the LightScanner has an edge over the ABI.

Clinicopathological features of gastric carcinoma in Ibadan, Nigeria, 2000-2011.

AIM: The most recent study on the clinicopathological features of gastric carcinoma from the University College Hospital (UCH), Ibadan, was done in 2000. The aim of this study is to update the knowledge on the clinicopathological features of gastric carcinoma diagnosed in the Pathology Department of the UCH Ibadan between 2000 and 2011. MATERIALS AND METHODS: This was a 12-year retrospective review of clinical and demographic data and the histopathological features of gastric cancers diagnosed at the Pathology Department of the UCH. The chi square test, Fisher's exact test, and the t-independent test were used as applicable in the statistical analyses. RESULTS: A total of 117 cases of gastric carcinoma were histologically diagnosed at the Pathology Department of UCH, Ibadan in this period giving a relative ratio frequency of 1.38% for all cancers. It represented 18.4% of all gastrointestinal tract malignancies diagnosed in the same period. There was a male preponderance with male:female ratio of 1.72:1; the middle-aged and elderly made up about 76.1% of cases. The disease was clinically and histologically advanced in 92.8% of cases. Gastric tumours were predominantly antral/ pyloric in 80% of cases and exophytic in 62.3% of cases. The intestinal histotype constituted 47.0% cases although a rise in the diffuse histological type was observed. CONCLUSION: There is a decline in the relative ratio frequency of gastric carcinoma in Ibadan; and a fall in the rate of the intestinal type of gastric carcinoma relative to the diffuse type when compared to previous studies from our centre.