PROGNOSTIC VALUE OF CHORIONIC-GONADOTROPIN BETA-GENE TRANSCRIPTS IN HUMAN BREAST-CARCINOMA

The beta subunit of human chorionic gonadotropin is potentially encode d by six genes, which can be categorized into two types based on a seq uence change at codon 117: GCC for the type I and GAC for the type II genes, We previously showed that, whereas type I genes were exclusivel y expressed in normal breast tissues, expression of type II genes was associated with malignant transformation (Bellet, D., et al, Cancer Re s., 57: 516-523, 1997), We designed a simple and robust test (the CG11 7 assay) that measures the percentage of type II over both types of ch orionic gonadotropin beta mRNAs, Normal breast tissues consistently ha d a negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0 to 100%, The prognostic significance of the CG117 inde x was investigated in a series of 99 unilateral invasive primary breas t cancer patients with known long-term outcome (median follow-up, 9 ye ars), The CG117 index was positive in 48 (48.5%) of the 99 tumor mRNA samples, The index was not significantly associated with standard prog nostic parameters, including clinical and macroscopic tumor size, hist opathological grade, and lymph node status or steroid receptor status, Patients with a positive CG117 index in primary tumor mRNA had signif icantly shorter metastasis-free survival (P = 0.014) and overall survi val (P = 0.038) after surgery, compared to patients with a negative in dex, The prognostic significance of the CG117 index persisted in Cox m ultivariate regression analysis, both for metastasis-free survival (P = 0.008) and overall survival (P = 0.016), together with lymph node st atus (P = 0.027 and P = 0.009, respectively), These findings indicate that the CG117 index may contribute to the identification of high-risk breast cancer patients.