Background: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. Methods: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. Results: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Background and Aims: Lymphovascular invasion (LVI) is an indicator of lymph node metastasis and poor prognosis in various cancers including squamous cell carcinoma (SCC). Despite being easily resectable and having little potential for LVI; SCC displays aggressive behavior and often results in the death of the patient. With this in mind, it may be useful to investigate the clinical, pathological, and microRNA expression profile associated with LVI in SCC.Methods: We evaluated the histological hallmarks associated with LVI from 16 formalin fixed paraffin embedded (FFPE) tissue samples (10 LVI−, 6 LVI+). We also quantified the expression of 10 microRNAs (hsa‐miR‐21‐5p, hsa‐miR‐21‐3p, hsa‐miR‐155‐5p, hsa‐miR‐196a‐5p, hsa‐miR‐375, hsa‐let‐7d‐5p, hsa‐miR‐146b‐3p, hsa‐miR‐221‐5p, hsa‐miR‐205‐5p, hsa‐miR‐491‐5p), which have been previously identified to play a role in SCC development, using real time‐PCR with the Qiagen miRCURY LNA SYBR Green PCR Kit.Results: We observed a significant upregulation of microRNA‐155, microRNA‐196a, microRNA‐375, and microRNA‐221 in cases with lymphovascular invasion. Morphologically, we identified poor differentiation, dysplasia, loss of membrane polarity, high nuclear to cytoplasmic ratio, and the presence of squamous nests as defining features of LVI. Additionally, we found a gender bias and observed a tendency toward lymphatic invasion in lesions presenting around the perineal and abdominal regions.Conclusion: We speculate that this profile may have prognostic significance and could guide the clinician in their treatment protocols for patients matching our genetic, demographic, and morphologic profile.

This study aimed to compare the degree of epigenetic modifications between a TB-HIV co-infected cohort and uninfected subjects. Formalin-fixed paraffin-embedded (FFPE) tissues were retrieved from 45 TB-HIV co-infected and 45 control individuals. Real-time PCR was applied to compare the level of expression of genes involved in epigenetic regulation. The protein multiplex assay was used to assess the degree of protein modification. DNA sequencing was used to determine the evolutionary relationships between the infecting HIV and Mtb strains. Our results indicated a significant increase in the expression of the five candidate genes in the patients with TB-HIV relative to the control cohort. A sharp increase in the degree of histone methylation, acetylation and phosphorylation was observed in TB-HIV co-infected patients. The phylogenetic analysis classified the strains into three distinct HIV clusters and five Mtb clusters. The disparities in the expression profiles of our candidate genes between the TB-HIV cohort and non-TB-HIV group highlights the important role played by various TB and HIV strains in regulating the host gene expression landscape.

Background: The immunohistochemical (IHC) detection of myelocytomatosis oncogene (MYC) is a crucial step in the diagnosis and prognosis of Burkitt lymphoma (BL). Sections of the MYC protein are routinely used as tags in protein precipitation experiments to assist with the isolation of proteins without antibodies. However, it is unknown if the tag antibodies can also be used for BL diagnosis. Aim: This project aimed to determine whether the MYC tag 9E10 antibody can be used to detect MYC overexpression because of MYC translocation in BL cases. Setting: Charlotte Maxeke Johannesburg Academic Hospital, South Africa. Methods: Immunohistochemical staining for 9E10 was optimised and used to stain 10 BL with known MYC translocation status to calculate sensitivity, specificity and predictive values. Results: Staining of the BL cases generally produced a ‘very weak’ (70%) and weak-moderate (18.2%) staining patterns with a staining extent of 1+ (36%) and 3+ (27%). Of the 10 samples, 6 (60%) showed a positive MYC protein expression by IHC. In comparison, 7 (70%) samples indicated MYC gene rearrangements. There were 5 (50%) cases with both MYC IHC expression and gene translocations and 2 (20%) cases that were negative for both MYC IHC and gene rearrangements. Conclusion: The authors demonstrate that the 9E10 MYC tagged antibody may be used to detect MYC gene expression with a sensitivity of 71% and a specificity of 67%. In addition, the positive predictive value (PPV) and negative predictive value (NPV) varied according to IHC staining cut-offs. Immunohistochemical expression does not perfectly correlate with translocation status because of inconsistencies with IHC interpretation. Contribution: MYC gene rearrangements are present in nearly all BL cases. Finding more affordable and convenient ways to predict the presence of MYC gene rearrangements is of utmost importance, given the lack of financial resources in our continent. This study shows that the 9E10 antibody, commonly used in protein tagging experiments, may also be used to predict MYC gene rearrangements in BL.