Determination of TGFβ1 protein level in human primary breast cancers and its relationship with survival

Abstract

Transforming growth factor-beta (TGFb)1 is thought to be implicated in breast cancer progression. However, data about the influence of TGFb1 on breast cancer development are conflicting. To clarify the clinical relevance of TGFb1, TGFb1 protein level has been measured by enzyme-immoassay in 193 breast tumour samples. We found that 94.3% of patients expressed TGFb1 with a range of 0 -684 pg mg À1 protein.In the overall population, an increase of tumoral TGFb1 was observed in premenopausal patients when compared to postmenopausal subgroup (P ¼ 0.0006). When patients were subdivided according to nodal status, TGFb1 was correlated to type-1 plasminogen activator inhibitor in the node-negative subgroup (P ¼ 0.040). Multivariate analysis revealed that, after lymph node status (P ¼ 0.0002) and urokinase-type plasminogen activator (P ¼ 0.004), TGFb1 was an independent prognostic marker for DFS (P ¼ 0.005) in the overall population. In the node-negative population, TGFb1 was the prominent prognostic factor (P ¼ 0.010). In the same population, Kaplan -Meier curves demonstrated that high TGFb1 level was correlated with a shorter diseasefree survival (P ¼ 0.020). These data suggest that the measurement of tumoral TGFb1 protein level, especially for node-negative patients, might help to identify a high-risk population early in tumour progression.

TGF-β1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival

“…ER-negative tumours had lower TGF-b1 than ER-positive ones if patients were node-negative. However, for node-positive patients, ER-positive tumours had lower TGF-b1 than ER-negative ones (Desruisseau et al, 2006). These findings seem to support the possibility that TGF-b1 may have different functions in breast cancer progression depending on the stage of the disease.…”

“…Most of the studies used semi-quantitative immunohistochemical staining to assess TGF-b1 levels in breast tumours. There was only one study using ELISA to measure TGF-b1 in tissue samples, and the study found high TGF-b1 in association with poor survival in nodenegative, but not in node-positive patients (Desruisseau et al, 2006). Studies also suggest possible synergies between TGF-b and insulin-like growth factors (IGFs) (Tsukazaki et al, 1994;Wong et al, 2001).…”

“…Several studies found high TGF-b1 being associated with poor survival (Gorsch et al, 1992;Walker and Dearing, 1992;Dalal et al, 1993;Walker et al, 1994;Desruisseau et al, 2006), whereas others showed an opposite association (Murray et al, 1993;Kesari et al, 1999). Most of the studies used semi-quantitative immunohistochemical staining to assess TGF-b1 levels in breast tumours.…”

Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

“…Numerous studies have shown the involvement of TGF-b1 in different types of cancer, including gastric, colorectal and breast cancer (Naef et al, 1997;Nakamura et al, 1998;Maehara et al, 1999;Saito et al, 1999;Desruisseau et al, 2006). Most of these studies assessed tissue TGF-b1 levels by mRNA expression, immunohistochemistry or serum TGF-b1 levels, which give either less information on the actual protein levels, are difficult to quantify or do not reflect local effects.…”

Tamoxifen decreases extracellular TGF-β1 secreted from breast cancer cells — A post-translational regulation involving matrix metalloproteinase activity

“…Excess TGF-β1 produced by tumor cells is suggested to act on the host to suppress immune surveillance, increase angiogenesis, and promote tumor cell survival and metastasis [6][7][8][9]. In breast cancer patients, an increased expression of TGF-β1 has been shown to correlate with metastatic disease and poor prognostic outcome [10][11][12]. Moreover, TGF-β1 activity may prime primary breast tumors for lung metastasis seeding [13].…”