Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. METHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. RESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. CONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

High triple-negative breast cancer prevalence and aggressive prognostic factors in Barbadian women with breast cancer.

BACKGROUND: Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry. METHODS: Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database. RESULTS: There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59 years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25% was observed, whereas TNBC prevalences of 21% and 10% were observed in NHBs and NHWs, respectively. CONCLUSIONS: The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was ~2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally.

Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women.

PURPOSE: Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women. METHODS: Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features. RESULTS: Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women. CONCLUSIONS: High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.

Prostate cancer incidence and mortality in barbados, west indies.

We describe prostate cancer incidence and mortality in Barbados, West Indies. We ascertained all histologically confirmed cases of prostate cancer during the period July 2002 to December 2008 and reviewed each death registration citing prostate cancer over a 14-year period commencing January 1995. There were 1101 new cases for an incidence rate of 160.4 (95% Confidence Interval: 151.0-170.2) per 100,000 standardized to the US population. Comparable rates in African-American and White American men were 248.2 (95% CI: 246.0-250.5) and 158.0 (95% CI: 157.5-158.6) per 100,000, respectively. Prostate cancer mortality rates in Barbados ranged from 63.2 to 101.6 per 100,000, compared to 51.1 to 78.8 per 100,000 among African Americans. Prostate cancer risks are lower in Caribbean-origin populations than previously believed, while mortality rates appeared to be higher than reported in African-American men. Studies in Caribbean populations may assist understanding of disparities among African-origin populations with shared heredity.

Myeloid sarcoma of the vagina: a report of 2 cases.

OBJECTIVE: To describe 2 cases of myeloid sarcoma of the vagina, in a patient without a history of acute myeloid leukemia (AML) and in another whose condition was previously diagnosed with AML. MATERIALS AND METHODS: The clinical histories of 2 patients whose conditions were diagnosed with myeloid sarcoma of the vagina were obtained from their medical records. RESULTS: Case 1: A 77-year-old woman with no systemic illnesses presented with a vaginal lump. Clinically, there was a 6-cm periurethral mass that was examined by biopsy. The histopathologic specimen was evaluated on routine and immunohistochemical stains, and myeloid sarcoma was diagnosed after extensive immunohistochemical analysis. The patient was treated with pelvic radiation. She developed extensive myeloid sarcoma of the skin and AML 4.5 months later; she died 2 weeks later, 5 months after the initial presentation. Case 2: A 36-year-old woman with a known history of AML who has had multiple leukemic and extramedullary recurrences presented with a pelvic mass. Physical findings revealed large masses in the vagina and rectovaginal septum, which were confirmed as myeloid sarcoma after biopsy and histologic examination. The patient was treated with pelvic/vaginal radiation. Five months later, she had another leukemic relapse and died within 1 day of palliative chemotherapy. CONCLUSIONS: Myeloid sarcoma of the vagina is extremely rare. Most patients have a poor prognosis and either have a history of or will subsequently develop AML.

A 6-year analysis of the clinicopathological profile of patients with prostate cancer at the University Hospital of the West Indies, Jamaica.

OBJECTIVE To document the clinicopathological characteristics of prostate cancer in a public hospital-based population in Jamaica, over a 6-year period, and examine any trends in these characteristics over time, as prostate cancer is the leading cause of cancer in Jamaican men, but there are few published reports documenting the clinicopathological profile of this disease in the Jamaican population. PATIENTS AND METHODS All patients consecutively diagnosed with prostate cancer by transrectal ultrasonography-guided biopsy at the University Hospital of the West Indies, from January 2000 to December 2005, were identified at time of diagnosis, and relevant clinical and pathological data collected from the accompanying histopathology request forms. RESULTS There were 529 cases of prostate cancer diagnosed over the 6 years. The mean (sd) age was 70.66 (8.74) years, with 137 patients aged 70-74 years. A serum prostate-specific antigen (PSA) level was obtained for 490 (92.6%) patients. Of these, an accurate PSA value was available for 456 (86.2%) patients and a 'minimum level' recorded for the remaining 34, all of whom had a PSA level of >100 ng/mL. Of the patients with available PSA information, only 91 (18.5%) had a level of < or =10.0 ng/mL. By contrast, 155 (31.6%) patients had levels of >100 ng/mL. The median (range, interquartile range) serum PSA level for those patients with accurate values was 30.7 (1-14 260, 11.7-109) ng/mL. Histologically, moderately and poorly differentiated cancers accounted for 198 (37.5%) and 160 (30.2%) cases, respectively. Correlation of the variables under investigation confirmed that there was a statistically significant positive and moderate correlation between serum PSA level and Gleason score (Spearman r 0.49; P < 0.001). Statistical analysis of all other variables, including the number of cases of prostate cancer diagnosed annually, showed no significant differences. CONCLUSION Compared with many countries, including some in the Caribbean, prostate cancer in Jamaican men is diagnosed when they are older and these patients have significantly higher PSA levels at diagnosis, suggesting more advanced disease. Despite increasing public awareness of prostate cancer, it appears that there has been no significant change in the profile of patients with prostate cancer, at the time of diagnosis, over the last 6 years, findings consistent with the absence of an organized screening programme for prostate cancer in Jamaica.