Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas

Aims: Loss of transforming growth factor beta type II receptor (TGF beta-RI I) expression has been associated with resistance to TGF beta-mediated inhi bition of cell proliferation and tumour progression. We investigated whethe r the expression of TGF beta-RII is related to the progression of human bre ast cancer and whether there is a correlation between TGF beta-RII expressi on and phenotypic markers of biological aggressiveness. Methods and results: Immunohistochemical methods were used to detect TGF be ta-RII in archival breast samples including benign proliferative lesions, d uctal carcinoma in situ (DCIS) and invasive mammary carcinomas (IMC). Neopl astic cells showed reduced expression of TGF beta-RII in comparison to the normal breast tissue and benign lesions. There was a significant inverse co rrelation between loss of TGF beta-RII expression and tumour grade within b oth DCIS (P = 0.004) and IMC (P = 0.001) groups. There was an inverse corre lation between TGF beta-RII expression and both mitotic count (P = 0.001) a nd clinical stage (P = 0.004). Oestrogen receptor (P = 0.07) and lymph node status (P = 0.10) were not significantly associated with TGF beta-RII expr ession. Conclusions: These data indicate that decreased expression of TGF beta-RII may contribute to breast cancer progression and is related to a more aggres sive phenotype in both in-situ and invasive carcinomas.