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
- Author:
Agboola AOJ
;
Banjo AAF
;
Anunobi CC
;
Ayoade BA
;
Deji-Agboola AM
;
Musa AA
;
Abdel-Fatah T
;
Nolan CC
;
Rakha EA
;
Ellis IO
;
Green AR
- Publication Type:Journal Article
- Keywords:
p53;
independent prognostic factor;
breast cancer;
Nigerian;
ethnicity
- MeSH:
Breast Neoplasms;
Genes, p53
- From:The Malaysian Journal of Pathology
2014;36(1):3-17
- CountryMalaysia
- Language:English
-
Abstract:
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.
- Full text:P020141217511838580893.pdf
