Diagnosis of Viral Diseases in Sudan: Coronaviruses Unveil the Concealed Venues

Establishing the diagnosis of viral diseases often needs sophisticated settings, equipment, expertise, and strict laboratory methods.  In Sudan, as in most developing countries, viral diseases are mostly diagnosed by clinical presentation. As most viral infections are self-limiting and there is no specific treatment for most of them, laboratory diagnosis has not been a focus for improvement, particularly in public sector until the current pandemic of COVID-19. During this pandemic, the vital need for well-equipped clinical virology laboratories is urged. The aim of this work is to highlight the various diagnostic methods and to describe the current situation of clinical virology diagnostics in Sudan

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Epstein-Barr virus (EBV) status in colorectal cancer: a mini review

Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC

Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

Abstract Background Cervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16INK4a in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia. Methods A total of 90 samples, diagnosed for cervical cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies using automated immunohistochemistry platform (ASLink 48-DAKO). Results Immunohistochemical protein expression of p16INK4a positivity was found to be highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The majority of cases (97.4%) were p16INK4a positive in the age group 41–60 years. In addition, a statistically significant difference between p16INK4a and HPV was observed among total cervical tumor cases and SCC cases. Conclusions As expected staining of invasive cervical cancer with anti-HPV showed rare positivity because HPV heralds active infection in dysplastic lesions and not of frank cervical carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in SCC and other cervical tumors

Immunohistochemistry defined subtypes of breast cancer in 678 Sudanese and Eritrean women; hospitals based case series

Abstract Background Breast cancer is the most common malignancy accounting for 25% of all cancers in females. In Africa, breast cancer prevalence and mortality are steadily increasing. Knowledge of hormone receptors and human epidermal growth factor receptor-2 (HER-2) expressions are vital for breast cancer management plans and decision making. There is wide regional variation in the proportion of these biomarkers, especially in African countries. Hormone receptors positivity in indigenous African and African American women is considered to be low and triple negative breast cancer is a dominant phenotype. There is paucity of data regarding hormone receptors (ER and PR) and HER2 expressions in North-eastern Africa (Eritrea and Sudan). The purpose of this study was to evaluate the expression of ER, PR and HER2 in Eritrean and Sudanese case series and correlate these biomarkers with the clinicopathological profile. Method Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR, and HER2) were assessed in consecutive female patients who had been diagnosed with invasive breast cancer from 2011 to 2015 in Gezira University Pathology Laboratory, the Sudan and National Health laboratory, Asmara, Eritrea. Results There were 678 cases involved in this study. The mean age was 48.8 years with ±0.53 standard error of the mean. Two-thirds of the case were ≤50 years. Invasive ductal carcinoma, no special type was the most dominant histologic type (86%) in both study groups. The majority of cases (70%) had tumour stage pT2 and pT3 and about 50% had lymph node involvement. Less than 5% of the cases had well-differentiated tumours. The ER, PR and HER2 positive rates were 45%, 32%, and 29%, respectively. The proportion of luminal-A like, luminal-B like, HER2 enriched and TNBC were 37%, 13%, 16% and 34%, respectively. Fisher extract analysis showed age (p = .015), tumour size (p = .041), and histologic grade (p = .000) were significantly associated with intrinsic subtypes. Furthermore, Logistic regression analysis stratified by origin, age, tumour size, lymph-node metastasis and grade indicated that younger women age (≤50 years) and grade III tumours were more likely to be diagnosed with ER negative breast cancer. Conclusion Most of Sudanese and Eritrean women were diagnosed at younger age and with unfavourable prognostic clinicopathologic prognostic markers. TNBC is more frequent in this cohort study; patients with grade III tumours and young age are more likely to be hormone receptors negative. Therefore, routine determination of hormone receptors is warranted for appropriate targeted therapy

Additional file 1: Table S1. of Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

Frequency of p16INK4a/Ki-67 immunostaining according to diagnosis and HPV infection in the 63 cervical tumor cases. (DOCX 51 kb

Comparison of Receptor-Defined Breast Cancer Subtypes Between German and Sudanese Women: A Facility-Based Cohort Study

Purpose: The objective of this study was to compare tumor characteristics, biomarkers, and surrogate subtypes of breast cancer between Sudanese and German women. Methods: Tumor characteristics and immunohistochemistry markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) were collected from the routine assessment of consecutive patients with invasive breast cancer diagnosed from 2010 to 2015 (Gezira University Pathology Laboratory, Gezira, Sudan) and from 1999 to 2013 (Breast Centre, Martin-Luther-University, Halle, Germany). Results: A total of 2,492 patients (German [n = 1,932] and Sudanese [n = 560]) were included. Age at diagnosis ranged from 20 to 94 years. Sudanese women were, on average, 10 years younger than German women, with a mean (± standard deviation) age of 48.8 (13.5) and 58.6 (12.4) years, respectively. The Sudanese women had a higher grade, larger tumor, and more lymph node positivity compared with German women. ER-, PR-, and HER2-negative proportions were 55%, 61.8%, and 71.3%, respectively, for Sudanese women versus 22.7%, 32.3%, and 82.5%, respectively, for German women. The triple-negative subtype was more prevalent in Sudanese women (34.5%) than in German women (14.2%). The strongest factor associated with ER-negative disease was grade III (odds ratio, 19.6; 95% CI 11.6 to 33.4; P < .001). Sudanese patients were at higher risk for ER-negative breast cancer, with an odds ratio of 2.01 (P = .001; adjusted for age, size, nodal status, histologic type, and grade). Stratified by grade, the influence of origin was observed in grade I and grade II tumors, but not in grade III tumors. Conclusion: Sudanese women had more aggressive tumor characteristics and unfavorable prognostic biomarkers. After adjustment, Sudanese origin was still associated with hormone receptor–negative disease, especially in grade I and II tumors. These findings suggest differences in tumor biology among these ethnic groups