Higher stromal expression of transforming growth factor-beta type II receptors is associated with poorer prognosis breast tumors

Transforming growth factor-beta (TGFB) is a potent inhibitor of normal epithelial cell proliferation, and may be one of the regulatory factors that are perturbed during tumor development. While many tumor cell lines no longer respond to the inhibitory effects of TGFB due to a reduction or absence of the type II receptor (TGFBR2), the role of TGFBR2 in tumors from patients with breast cancer is less clear. The objective of this study was to screen human breast tumors to determine if there was a TGFBR2 mutation and/or altered expression of TGFBR2 protein. Using 10 unique primers, SSCP-PCR was used to detect heterozygosity in the complete coding sequence from 72 tumors and normal DNA from 20 individuals. One region of the promoter was also examined. Expression of TGFBR2 in the same breast tumors was examined by immunohistochemistry. Sequence variations were identified among normal and tumor tissue samples by SSCP-PCR within coding regions of exon 4 (1/72 samples) and within non-coding regions of intron 2 (1/72), intron 3 (72/72), and intron 6 (1/72). A new polymorphism was identified in intron 3. Observed allele frequencies were consistent with Hardy-Weinberg equilibrium in both the tumors and normal DNA. TGFBR2 was expressed in the epithelium and stroma of tumor tissue. The percentage of cells expressing TGFBR2 in stroma was higher in patients that had a positive lymph node status and/or negative estrogen and progesterone receptor expression. There was no relationship between TGFBR2 expression in the epithelium and these variables.