Vitamin D receptor, Retinoid X receptor and peroxisome proliferator-activated receptor γ are overexpressed in BRCA1 mutated breast cancer and predict prognosis.

BACKGROUND: BRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation. Vitamin D Receptor (VDR), Retinoid X Receptor (RXR) and Peroxisome Proliferator-activated Receptor γ (PPARγ) are known to interact with TRs by forming functional heterodimers. Whether VDR, RXR or PPARγ are expressed in BRCA1 mutated breast cancer or may even be present in case of triple negativity is not known. Hence the current study aimed to investigate VDR, RXR and PPARγ in BRCA1 mut breast cancer and to test whether any of the three may be associated with clinico-pathological criteria including overall survival. METHODS: This study analyzed VDR, RXR and PPARγ by immunohistochemistry in BRCA1 associated (n = 38) and sporadic breast cancer (n = 79). Receptors were quantified by applying an established scoring system (IR-score) and were tested for association with clinico-pathological variables. RESULTS: VDR, RXR and PPARγ were detected in over 90% of triple negative BRCA1 mut breast cancer and were significantly (VDR: p < 0.001, RXR: p = 0.010, PPARγ: p < 0.001) overexpressed in BRCA1 mutated as compared to sporadic cancer cases. VDR and RXR positivity predicted prolonged overall survival only in BRCA1 mutated cases while such association was not observed in sporadic breast cancer. CONCLUSIONS: In conclusion, this is the first study to describe VDR, RXR and PPARγ in BRCA1 mutated breast cancer. Based on the data presented here these receptors may be hypothesized to potentially evolve as interesting markers or even targets in hereditary breast cancer. However, independent studies are indispensable thus to confirm this hypothesis.

Compartmental differences of circulating tumor cells in colorectal cancer.

BACKGROUND: The prognostic role of circulating tumor cells (CTCs) has been established for colorectal cancer (CRC). We investigated the qualitative and quantitative detection of CTC in the central (CVBC) and mesenteric (MVBC) venous blood compartments to elucidate the patterns of hematogenous tumor cell dissemination in patients with CRC. METHODS: A total of 200 patients were enrolled prospectively. Blood samples were collected from the tumor-draining vein and via a central venous line. CTCs were detected and quantified by using the CellSearch system. Factors associated with CTC detection in both compartments were analyzed by using univariate and multivariate analyses. RESULTS: CTC analyses were performed in the CVBC and MVBC in 200 and 80 patients, respectively. CTCs were found at a higher rate (P=0.01) and at a higher count (P=0.006) in the MVBC compared with the CVBC. On multivariate analyses, stage IV disease (odds ratio, 3.83; 95% confidence interval, 1.42-10.35) and increased preoperative carbohydrate antigen 19-9 level (odds ratio, 3.57; 1.30-9.79) were associated with CTC detection in the CVBC. CTCs were detected more frequently (P=0.05) and at higher numbers (P=0.05) in the CVBC of patients with low compared with mid or high rectal tumors. CONCLUSIONS: The qualitative and quantitative detection of CTCs is higher in the MVBC compared with the CVBC of patients with CRC.