mRNA expression level of estrogen-inducible gene, α 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers

Abstract

We previously identified 18 genes that correlated with ER positivity by adapter-tagged competitive-PCR analysis of 2412 genes in human breast cancer tissues. The aim of the present study was to determine the prognostic significance of these genes. mRNA expression levels of 12 of the above 18 genes were quantified in breast cancer tissues by real-time PCR assay, and their association with patients' prognosis (n=110) was studied according to hormone receptor (HR) status. In addition, the genes found to influence prognosis were further investigated to examine whether their mRNA expression could be induced by estrogen in MCF-7 cells in vitro. Of the 12 genes, mRNA expression levels of two [α1-antichymotrypsin (ACT) and stanniocalcin 2 (STC2)] were significantly (P=0.002 and P=0.007, respectively) associated with good prognosis in HR-positive (ER and/or PR positive) breast cancer patients treated with adjuvant hormone therapy. Multivariate analysis showed that ACT mRNA level, but not STC2 mRNA level, in HR-positive patients, was a significant prognostic factor (P=0.042), which was independent of tumor size and lymph node metastases. On the other hand, mRNA expressions of ACT and STC2 were not significantly associated with prognosis in HR-negative patients. Estradiol treatment resulted in a significant increase in the mRNA levels of both ACT and STC2 in MCF-7 cells. The mRNA level of ACT, which is an estrogen-inducible gene, is a significant predictor of good prognosis in HR-positive, but not HR-negative, patients with breast cancers. Since HR-positive patients were treated with adjuvant hormone therapy, we suggest that ACT mRNA level could potentially be used as a predictor of response to hormone therapy, rather than a prognostic factor (predictor of metastatic potential).