1.Molecular profiling of breast cancer in Nigerian women identifies an altered p53 pathway as a major mechanism underlying its poor prognosis compared with British counterpart
Agboola AOJ ; Banjo AAF ; Anunobi CC ; Ayoade BA ; Deji-Agboola AM ; Musa AA ; Abdel-Fatah T ; Nolan CC ; Rakha EA ; Ellis IO ; Green AR
The Malaysian Journal of Pathology 2014;36(1):3-17
Advances in breast cancer (BC) research have demonstrated differences between black and white women with regarding tumour behaviour, patient outcome and response to treatment
which can be explained by underlying genetic changes. The tumour suppressor gene p53 has been speculated to be involved in tumour biology of triple negative and/or basal –like BC and more commonly observed in black than caucasian women. Materials and methods: In this study, the
protein expression of p53 was investigated in tissue samples from a series of 308 Nigerian women,
prepared as a tissue microarray (TMA), using immunohistochemistry. Clinicopathological parameters,
biomarkers of functional significance in BC and patient outcome of tumours expressing p53 in
Nigerian women were correlated with UK grade matched series. Results: A significantly large
proportion of BC from Nigerian women showed high p53 expression compared with UK women
(p<0.001). In those tumours showing positive p53 in the Nigerian series, a significant proportion were
premenopausal, diagnosed before 50 years, larger in size, with evidence of metastasis into lymphatic
vessels ( all p<0.001). In addition, p53 positive expression was also significantly correlated with
negative expression of ER and PgR (p<0.001, p<0.03 respectively), BRCA1, MDM2 (all p<0.001),
p21 (p=0.006) and E-cadherin (p=0.001) and positively associated with P-cadherin (p=0.001),
triple negative phenotype, basal cytokeratin (CK) 5/6 expression (p<0.04) and basal phenotype
compared with the UK series (p<0.001). Survival analyses showed Nigerian women with BC were
significantly associated with poor BC specific survival (p<0.001, but no significant association with
disease free interval was observed. Conclusion: In this study, protein expressions of p53 pathways
are different between Nigerian and UK BC women and this may also contribute to differences in
tumour biology. Therefore, targeting these p53 pathways for therapeutic usage might improve the
poor outcome observed in Black Nigerian women.
Breast Neoplasms
;
Genes, p53
2.Tumour cell membrane laminin expression is associated with basal-like phenotype and poor survival in Nigerian breast cancer
Agboola Aoj ; Ebili Ho ; Iyawe Vo ; Banjo Aaf ; Salami Bs ; Rakha Ea ; Nolan C ; Ellis Io ; Green Ar
The Malaysian Journal of Pathology 2016;38(2):83-92
Introduction: Laminin is a glycoprotein with diverse functions in carcinogenesis including cell
proliferation, invasion, metastases and epithelial-mesenchymal transition (EMT). In breast cancer
(BC) laminin expression is speculated to be associated with unfavourable clinicopathological and
molecular characteristics. We hypothesize that laminin expression would contributed to the aggressive
nature of basal like and triple negative BC phenotype observed in Black women. Methods: The
expression of laminin was determined in a well-characterised Nigerian cohort of 255 BC using tissue
microarray and immunohistochemistry. Laminin expression was compared with clinical, pathological
and survival characteristics. Results: Laminin was expressed in 146 (57.3%) cases and significantly
correlated with younger age at diagnosis (p=0.005), premenopausal status (p=0.003), expression
of EGFR (p=0.002), ID4 and MTA1, basal cytokeratin 5/6, p53, and triple negative tumours (all
p<0.001). In addition, there was an inverse association of laminin expression with E-cadherin (p=0.03),
ER and PgR (all p<0.001) and a trend with BRCA1 (p=0.05). Univariate survival analysis showed
tumours positive for laminin had significantly poorer breast cancer specific survival (BCSS, p=0.009)
and disease free interval (p=0.03), but not associated in Cox multivariate analysis. Conclusion:
This study demonstrates that laminin expression may have important roles in the aggressive nature
observed in the basal-like and triple negative molecular subtype of Nigerian BC women.