B. A. Ayoade

Molecular characteristics and prognostic features of breast cancer in Nigerian compared with UK women

Although breast cancer (BC) incidence is lower in African–American women compared with White-American, in African countries such as Nigeria, BC is a common disease. Nigerian women have a higher risk for early-onset, with a high mortality rate from BC, prompting speculation that risk factors could be genetic and the molecular portrait of these tumours are different to those of western women. In this study, 308 BC samples from Nigerian women with complete clinical history and tumour characteristics were included and compared with a large series of BC from the UK as a control group. Immunoprofile of these tumours was characterised using a panel of 11 biomarkers of known relevance to BC. The immunoprofile and patients’ outcome were compared with tumour grade-matched UK control group. Nigerian women presenting with BC were more frequently premenopausal, and their tumours were characterised by large primary tumour size, high tumour grade, advanced lymph node stage, and a higher rate of vascular invasion compared with UK women. In the grade-matched groups, Nigerian BC showed over representation of triple–negative and basal phenotypes and BRCA1 deficiency BC compared with UK women, but no difference was found regarding HER2 expression between the two series. Nigerian women showed significantly poorer outcome after development of BC compared with UK women. This study demonstrates that there are possible genetic and molecular differences between an indigenous Black population and a UK-based series. The basal-like, triple negative and BRCA1 dysfunction groups of tumours identified in this study may have implications in the development of screening programs and therapies for African patients and families that are likely to have a BRCA1 dysfunction, basal like and triple negative.

Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women.

The majority of breast cancers (BC) in Nigerian women are triple negative and show breast cancer-associated gene 1 (BRCA1) deficiency as well as the basal like phenotype, with a high mortality rate. In contrast to the well-defined predictive factors for the hormonal therapy, there is a paucity of information on the BRCA1 deficiency breast tumor biology, particularly among African women. BRCA1 Sumoylation (UBC9) has been speculated to be involved in the ER transcription activity, BRCA1 deficiency and triple negative BC. We therefore hypothesized that UBC9, a SUMOylation marker, may have contributed to the aggressive nature of BRCA1 tumor phenotype observed in Nigerian women. This study investigated the immunoprofiles of UBC9 in tissue microarray (TMA) of 199 Nigerian women and correlated their protein expression with clinical outcome, pathological responses and the expression of other biomarkers to demonstrate the functional significance in Nigerian women. The protein expression of UBC9, as compared with other biomarkers, showed an inverse correlation with steroid hormones (ER, progesterone (PgR)), BRCA1, p27, p21 and MDM4, and a positive correlation with triple negative, basal cytokeratins (CK14 and CK5/6), epidermal growth factor receptor (EGFR), basal-like breast cancer phenotype, p53, phosphoinositide-3-kinases (PI3KCA), placental cadherin, (P-cadherin) and BRCA1 regulators (metastasis tumor antigen-1 (MTA1). Survival analysis showed that those tumors positive for UBC9 expression had a significantly poorer breast cancer-specific survival (BCSS) as compared with those showing negative expression. UBC9 remained an independent predictor of outcome for BCSS. This study demonstrates that UBC9 appears to play an important role in the tumor biology of Nigerian women. Therefore, a novel UBC9 targeted therapy in black women with BC could enhance a better patient outcome.

PIASγ expression in relation to clinicopathological, tumour factors and survival in indigenous black breast cancer women

Aim Indigenous black women with breast cancer (BC) show a high frequency of triple negative breast cancer (TNBC) comprising ER-, PR- and HER2- phenotypes and BRCA1 deficiency together with a high mortality rate, prompting speculation that risk factors could be genetic and the molecular portrait of these tumours may be different to those of Western women. Protein inhibitor of activated signal transducer (PIAS) γ implicated in the BRCA1 deficiency and triple negative BC was investigated to establish the relationship among the small ubiquitin-like modifier marker, pathological features, biomarkers expression and clinical outcome in the black women. Materials and methods This study investigated the immunoprofiles of PIASγ in 231 Nigerian BC prepared as tissue microarrays and correlated their protein expression with clinical outcome, pathological responses and the expression of 14 other relevant biomarkers. Results PIASγ protein expression showed a significant correlation with higher histological grade, basal-like biomarkers expression (CK14, CK5/6 and EGFR), BRCA1 regulator (MTA1), p53, PI3KCA, basal-like phenotype and TNBC. Also, an inverse correlation with steroid hormones (ER and PgR), p27, MDM4, mucin 1 and BRCA1 was observed with PIASγ expression. Univariate and multivariate survival analyses showed PIASγ expression was a predictor of poor outcome independent of tumour histological grade and ER expression. Conclusions PIASγ appears to be important in breast cancer behaviour arising from Nigerian women. PIASγ may therefore be useful for the screening of basal-like and TNBC. Also, development of novel therapies towards targeting PIASγ functional pathways may enhance the BC management among this ethnic nationality.

Clinical Features and Pattern of Presentation of Breast Diseases in Surgical Outpatient Clinic of a Suburban Tertiary Hospital in South-West Nigeria

Objective: To characterize the clinical features and pattern of presentation of breast diseases as observed in our practice. Materials and Methods: A prospective study of 121 consecutive patients with breast complaints presenting in our Surgical Outpatient Clinics. The relevant data were collected by two surgeons using the prescribed forms and was analyzed using Epi Info 2003, Mann-Whitney (test of two groups) Chi-squared and Fishers exact test was used to compare parameters of benign and malignant groups. P value <0.05 was considered as significant. Results: One hundred and nineteen patients were females, two were males. The age range was 14-70 years. Forty two (34.7%) patients were in the 21-30 year age group. The commonest symptoms were breast lump in 111 (91.7%) patients, and breast pain in 28 (23.1%) patients. Breast pain was a significant presenting complaint in patients with breast malignancy (P=.026). On clinical examination 103 (85.1%) patients had palpable lumps, and seven patients were normal. Forty four patients (36.3%) had malignant disease, seventy patients (57.8%) had benign breast diseases and seven were normal. Fifty nine of the 70 benign diseases were fibroadenoma. One hundred and three patients (85%) had appropriate therapy, while 18 patients (14.8%), including eight with malignant disease absconded. Conclusion: In the study, a breast lump was the commonest clinical feature of breast disease. Over 60% of these were benign. Breast pain was a statistically significant presentation in patients with malignant breast disease. One in seven of the patients absconded.