The authors have investigated the expression of
the microcephalin (MCPH1) protein to evaluate its prognostic
importance in breast cancer. Microcephalin is a
damage response protein involved in the regulation of
BRCA1 and BRCA2. BRCA1 mutations are often associated
with basal-like breast cancer, which are also often
negative for oestrogen receptor (ER), progesterone receptor
(PR) and HER2. MCPH1 immunohistochemistry was performed
on 319 breast cancers prepared as tissue microarray
and correlated with pathology, survival, ER, PR, HER2,
EGFR, CK5/6, CK14 and BRCA1 expression. After performing
continuous data analysis, mean microcephalin
expression decreased with increasing grade (P.006).
Mean microcephalin expression was lower in ER/PR negative
(P.001) and triple negative cancers (P.004).
Conversely, an association with HER2-positive cancers
was also identified (P.034). Reduced microcephalin
also correlated with reduced nuclear BRCA1 staining
(P.001). No association was identified with basal
markers. After dichotomising the data into low and high
microcephalin expression, reduced expression was identified
in 29% (93/319) of breast cancers. An association with
low expression was identified in invasive ductal carcinomas
with breast cancer-specific survival (BCSS) (P =
0.052). Multivariate analysis of ductal carcinomas showed
that microcephalin, together with lymph node involvement
and tumour size were independent predictors of BCSS
(P = 0.037). Microcephalin expression is reduced in 29%
of breast cancers, particularly in higher grade tumours and
BRCA1-negative cases. Microcephalin is an independent
predictor of BCSS in invasive ductal breast cancer patients
and may prove to be a useful biomarker for the identification
of aggressive breast cancers.