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VOLUME 15, 2014  Issue Number 19 , 8441-8445
DownLoad : 8441-8445 7.22 Wan Faiziah Wan Abdul Rahman.pdf
Expression of DNA Methylation Marker of Paired-Like Homeodomain Transcription Factor 2 and Growth Receptors in Invasive Ductal Carcinoma of the Breast
Wan Faiziah Wan Abdul Rahman et al
Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast
carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis.
We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and
its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR)
and human epidermal growth receptor 2 (HER2). Methods: We conducted a cross sectional study using 100
samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained
them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed
with chromogenic in-situ hybridization (CISH). Results: PITX2 protein was expressed in 53% of invasive ductal
carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between
PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with
molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also
significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most
significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). Conclusion: PITX2 is
another potential prognostic marker in breast carcinoma adding significant information to established prognostic
factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.
Key Words: PITX2 - hypermethylation - IHC - invasive ductal carcinoma - growth receptors - prognostic marker
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