Expression of DNA Methylation Marker of Paired-Like Homeodomain Transcription Factor 2 and Growth Receptors in Invasive Ductal Carcinoma of the Breast


Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breastcarcinoma 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 andits 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 100samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stainedthem with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmedwith chromogenic in-situ hybridization (CISH).
Results: PITX2 protein was expressed in 53% of invasive ductalcarcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association betweenPITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association withmolecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was alsosignificantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the mostsignificant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).
Conclusion: PITX2 isanother potential prognostic marker in breast carcinoma adding significant information to established prognosticfactors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.