No abstract

The objective of this study was to determine the conversion rate of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) between primary tumors and metastatic lesions in advanced breast cancer. Patients with suspected diagnosis of locally recurrent or metastatic breast cancer, either at first relapse or after successive disease progressions, who had an appropriately preserved sample from a primary tumor and were scheduled for a biopsy of the recurrent lesion, were included. Blinded determinations of receptor status on paired samples were performed by immunohistochemistry and fluorescence in situ hybridization at a central laboratory and compared with those performed locally. Overall, 196 patients were included and 184 patients were considered evaluable. Reasons for non-evaluability included the inability to perform biopsy (n = 4) or biopsy results showing normal tissue (n = 3), benign disease (n = 3) or a second neoplasia (n = 2). Conversion rates determined at local level were higher than those determined centrally (HER2: 16 vs. 3 %, ER: 21 vs. 13 %, PR: 35 vs. 28 %, respectively). There was substantial agreement regarding the expression of HER2 in primary tumors and metastases, and ER at metastases, between local and central laboratories. PR at any site and ER at primary site showed moderate agreement. Oncologists altered their treatment plans in 31 % of patients whose tumor subtype had changed. These results reinforce the recommendation for performing confirmatory biopsies of metastases, not only to avoid misdiagnosis of breast cancer relapse, but also to optimize treatment (clinicaltrials.gov identifier: NCT01377363).

No abstract

No abstract

52 Background: MicroRNAs regulate numerous aspects of normal and pathological cellular processes, including cancer. Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary (GU) tumors. miRNAs may also be considered as potential therapeutic targets when overexpression is associated to pathogenic effect. miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. The aim of this work is identify miRNAs potentially useful for CTC detection in blood samples from patients with GU tumors: bladder, prostate and renal tumors. Methods: miRGator, miRBase, smiRNAdb, GeneHUB-GEPIS, microRNA.org and miRNAMap free databases were used in order to identify miRNAs as biomarkers for CTC detection. In silico data were used to identify miRNAs highly expressed in GU tumors, but absent in hematopoietic-derived sources. RNA enriched in miRNAs was isolated from: GU tumors (bladder: HT1376, HT1197; prostate: VCaP, LNCaP and renal: ACHN, A704) and hematopoietic cell lines, GU tumor tissues (N= 6) and healthy blood samples (N= 19). mirVana miRNA and RiboPure Blood isolation kits were used. Using qRT-PCR miRNAs tumor-related were amplified. Results: Bioinformatic analysis included tissue-specific and oncogenic miRNAs and showed that mir-31, mir-136, mir-133a, mir-145, mir-187, mir-200a, mir-200b, mir-200c, mir-368 and hsa-let-7c levels were up-regulated in tumor tissues from patients with advanced GU tumors. For instance, relative expression of mir-31 was 6-timeshigher in bladder cell lines than in normal peripheral blood, mir-200c was 104-times higher in renal tumor tissue than in normal peripheral blood and finally hsa-let-7c was 3-times higher in prostate tumor tissue than in healthy blood samples. Conclusions: These results suggest that this bioinformatic approach is an useful high-throughout method to identified GU tumors-associated miRNAs. The selected miRNAs should be further evaluated for their potential as markers for CTC detection, prognosis and therapeutic outcome. This work was supported by Grants PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.