The survival of patients with hepatocellular carcinoma (HCC) is often individually

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. in the increased expression of and and Nutlin 3b the loss of expression accompanied by morphological changes enhanced tumorigenesis and loss of Gd-EOB-DTPA uptake This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms especially in the early stage of disease. gene expression in the tumor (10 11 However atypical Gd-EOB-DTPA uptake in the hepatobiliary phase is observed in the remaining 15% of HCCs and the molecular phenotype and clinical features of these HCCs remain to be elucidated. We hypothesized that EOB-MRI findings may vary in different tumor subtypes with unique biology. Therefore in this study we evaluated the molecular profiles of HCCs in a single institute cohort decided from Rabbit Polyclonal to CNKSR1. your EOB-MRI findings using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) microarray and immunohistochemistry (IHC) analyses. To clarify the clinical utility of the EOB-MRI findings we also evaluated the prognosis of a multicenter cohort of patients with early-stage HCC who underwent radical resection. Materials and Methods Patients A total of 417 patients who received surgical resection for HCC were enrolled in this study. Seventy patients underwent EOB-MRI for the diagnosis of HCC and received surgical resection at Kanazawa University or college Hospital from 2008 to 2011 Survival analysis was performed in this single-institute cohort (Cohort 1 and prognosis was evaluated every 6 months. The final evaluation of survival was performed in October 2011. From these 70 patients 62 tumor and non-tumor samples were snap-frozen in liquid nitrogen and utilized for qRT-PCR. For microarray analysis we assessed 238 patients who received surgical resection Nutlin 3b of HCC at the Liver Malignancy Institute of Fudan University or college. EOB-MRI was not performed in these patients because Gd-EOB-DTPA had not yet been launched in China. Their clinicopathologic characteristics and prognostic data have been explained previously (12). To evaluate the survival of early-stage HCCs we enrolled 109 patients who received EOB-MRI and surgical resection at Tokyo Medical and Dental care University Hospital Tokyo Women’s Medical University or college Hospital Nihon University or college School of Medicine Itabashi Hospital Niigata University or college Medical & Dental care Hospital Hyogo College of Medicine Hospital or Kurume University or college Hospital from 2008 to 2009 (Cohort 2). The prognosis of these patients was evaluated every year and the final evaluation of survival was performed in February 2012. This study was approved by the institutional review table at each study center and all patients provided written informed consent. EOB-MRI EOB-MRI was performed before surgical resection using a 1.5 or 3.0 Tesla MRI system with a fat-suppressed 2D or 3D gradient echo T1-weighted sequence (TR/TE = 3.2-3.6/1.6-2.3 ms flip angle 10 field of view 33-42 cm matrix 128-192 × 256-512 slice thickness 4.0-8.0 mm). A dose of 0.025 mmol/kg Gd-EOB-DTPA (Primovist; Bayer Schering Pharma Berlin Germany) was injected Nutlin 3b Nutlin 3b intravenously and the hepatobiliary phase was obtained at 15 min after the injection. All abdominal MRI data of the HCC patients were generated at Kanazawa University or college Hospital and image analysis was performed Nutlin 3b retrospectively by two radiologists (A.K. and O.M.) without knowledge of the clinical and pathological results. The signal intensity (SI) of the tumor was measured within the region of interest which was decided as the maximum oval area at the largest section of the tumor. The SI of the Nutlin 3b adjacent background liver was also measured within a region of interest of the same size while avoiding large vessels. The nodules were classified into the two following types: hypo-intense HCC which was defined as showing a lower SI than that of the surrounding liver (tumor SI/background SI < 1.0) in the hepatobiliary phase; and hyper-intense HCC which was defined as showing an equal or higher SI (tumor SI/background SI ≥ 1.0). For the mouse study EOB-MRI was performed using a 0.4 Tesla MRI system with a fat-suppressed 3D gradient echo T1-weighted sequence (TR/TE=66.5/4.0 ms flip angle 40° field of view 10 cm matrix 224 × 192 slice thickness 1.0 mm). A dose of 0.025 mmol/kg Gd-EOB-DTPA (Bayer Schering Pharma) was injected through the tail vein and the hepatobiliary phase was obtained at 12-20 min after the injection. Xenotransplantation of main HCC in.