Immunohistochemistry Expression of Programmed Death-Ligand 1 in Colorectal Carcinoma among Nigerians.

Background: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in Nigeria with a dismal 5-year survival rate. Interactions between the CD8+ T-lymphocytes and the immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) expressions are important. Novel antibodies have been developed against these immune checkpoints and have been found to improve clinical outcome in many solid organ malignancies.

Generative adversarial networks accurately reconstruct pan-cancer histology from pathologic, genomic, and radiographic latent features.

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of molecular features. These approaches distill cancer histologic images into high-level features, which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network-HistoXGAN-capable of reconstructing representative histology using feature vectors produced by common feature extractors.

Generative Adversarial Networks Accurately Reconstruct Pan-Cancer Histology from Pathologic, Genomic, and Radiographic Latent Features.

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network - HistoXGAN - capable of reconstructing representative histology using feature vectors produced by common feature extractors.

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.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than is mutation to the gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein.

Expression analysis of BACH1 with clinical variables using the US breast cancer patient cohort.

Background: Studies on functional roles of BACH1 reveal that BACH1 promotes cancer metastasis and regulates metabolic networks for metastatic processes. However, little is known about BACH1 protein expression in breast tumors and its relevance to clinical variables as a biomarker for patients with breast tumors.

Methods: Using a tissue microarray (TMA) of breast tumor tissues isolated from a patient cohort (N = 130) expression of BACH1 and its target gene MCT1 (encoded by SLC16A1) were monitored by immunohistochemistry (IHC) assays and scored for further analyses.

Increased Otoferlin Expression in B Cells Is Associated with Muscle Weakness in Untreated Juvenile Dermatomyositis: A Pilot Study.

Otoferlin mRNA expression is increased in JDM patients' PBMCs and muscle compared to healthy controls. This study aims to evaluate the role of otoferlin in JDM disease pathophysiology and its association with disease activity in untreated children with JDM. A total of 26 untreated JDM (88.

Molecular profiling of a real-world breast cancer cohort with genetically inferred ancestries reveals actionable tumor biology differences between European ancestry and African ancestry patient populations.

Background: Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways.

Integration of clinical features and deep learning on pathology for the prediction of breast cancer recurrence assays and risk of recurrence.

Gene expression-based recurrence assays are strongly recommended to guide the use of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but such testing is expensive, can contribute to delays in care, and may not be available in low-resource settings. Here, we describe the training and independent validation of a deep learning model that predicts recurrence assay result and risk of recurrence using both digital histology and clinical risk factors. We demonstrate that this approach outperforms an established clinical nomogram (area under the receiver operating characteristic curve of 0.

Immunohistochemical Study and Clinicopathologic Correlation of Cox-2 and Her-2 Expression in Colorectal Carcinoma: A 5-Year Retrospective Study.

Background: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects.

Objectives: To evaluate the expression of COX-2 and HER-2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer.

An enhancer variant associated with breast cancer susceptibility in Black women regulates TNFSF10 expression and antitumor immunity in triple-negative breast cancer.

Women of African ancestry have the highest mortality from triple-negative breast cancer (TNBC) of all racial groups. To understand the genomic basis of breast cancer in the populations, we previously conducted genome-wide association studies and identified single nucleotide polymorphisms (SNPs) associated with breast cancer in Black women. In this study, we investigated the functional significance of the top associated SNP rs13074711.

p50 mono-ubiquitination and interaction with BARD1 regulates cell cycle progression and maintains genome stability.

p50, the mature product of NFKB1, is constitutively produced from its precursor, p105. Here, we identify BARD1 as a p50-interacting factor. p50 directly associates with the BARD1 BRCT domains via a C-terminal phospho-serine motif.

Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.

Over 80% of triple-negative breast cancers (TNBC) express mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis. In this study, we dissected the function and association between mtp53 and PARP using a number of different cell lines, patient-derived xenografts (PDX), tissue microarrays (TMA), and The Cancer Genome Atlas (TCGA) database.

Radiogenomics of breast cancer using dynamic contrast enhanced MRI and gene expression profiling.

Background: Imaging techniques can provide information about the tumor non-invasively and have been shown to provide information about the underlying genetic makeup. Correlating image-based phenotypes (radiomics) with genomic analyses is an emerging area of research commonly referred to as "radiogenomics" or "imaging-genomics". The purpose of this study was to assess the potential for using an automated, quantitative radiomics platform on magnetic resonance (MR) breast imaging for inferring underlying activity of clinically relevant gene pathways derived from RNA sequencing of invasive breast cancers prior to therapy.

Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample.

Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer.

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice.

[Application of tissue-marking dyes for pathologic examination of surgical and autopsy specimens].

Objective: To assess the applicability of imported tissue-marking dyes and the samples of experimental dyes and decorative acrylic paints to mark the resection margins of a surgical specimen.

Material And Methods: Three sets of tissue-marking dyes: 2 imported sets and 1 experimental set, each containing red, orange, yellow, green, blue, purple, and black dyes, and a set of decorative acrylic paints containing black, blue, light blue, green, yellow, ocher, orange, magenta, and purple dyes. The experimental dyes and imported ones were used to mark tonsillar fragments obtained at tonsillectomy.

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc.

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in Mutation Carriers.

Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene.

Household air pollution and chronic hypoxia in the placenta of pregnant Nigerian women: A randomized controlled ethanol Cookstove intervention.

Background: Household air pollution (HAP) is associated with adverse pregnancy outcomes.

Objectives: Investigate impact of in-utero HAP exposure on placental development and chronic hypoxia.

Methods: Markers of chronic placental hypoxia [Hofbauer cells (HBC), syncytial knots (SK), chorionic vascular density (cVD) and hypoxia-inducible factor (HIF)] were stained by hematoxylin-eosin and/or immunohistochemically in placenta samples collected from firewood-/kerosene-users (A,n=16), and ethanol-users (B,n=20) that participated in a randomized controlled intervention trial in Ibadan, Nigeria.