(HEPATOLOGY 2011;) See Editorial on Page 1427 This work was undertaken to address two issues raised in an editorial about our previous article16: (1) testing the accuracy of HCC immunomarkers in a homogeneous series of HCCs up to 2 cm in size and (2) improving the accuracy of the panel with additional markers. To this end, we retrospectively evaluated a series of HCCs consecutively diagnosed

on core biopsy samples with a 20- to 21-gauge needle; with this material, we tested the diagnostic accuracy of a refined panel of markers (CHC, GPC3, HSP70, and GS). The performance of the panel was also evaluated according to HCC grading [grade 1 (G1) versus grade 2 (G2)/grade 3 (G3)] and sizes (≤2 versus >2 cm). 3M, three-marker; 4M, four-marker; AASLD, American Roxadustat manufacturer Association for the Study Palbociclib of Liver Diseases; CHC, clathrin heavy chain; G1, grade 1; G2, grade 2; G3, grade 3; GPC3, glypican 3; GS, glutamine synthetase; H&E, hematoxylin and eosin; HCC, hepatocellular carcinoma; HGDN, high-grade dysplastic nodule; HSP70, heat shock protein 70; LGDN, low-grade dysplastic nodule. The series

under study was composed of 20- to 21-gauge needle core biopsy samples from 86 HCCs with a cirrhotic background. They were obtained from the files of the Policlinico General Hospital (Milan, Italy) and Melegnano General Hospital (Melegnano, Italy) and were collected from 2005 to 2009. The diagnosis of HCC was made in all the cases according to AASLD guidelines.17 The diagnostic process included routine laboratory tests, serum alpha-fetoprotein measurements, and abdominal ultrasound, contrast-enhanced spiral computed tomography, or magnetic resonance imaging. The diagnosis of cirrhosis was based on histology or concordant laboratory and imaging findings. The tumor size was the largest diameter measured by imaging. The histopathological diagnosis of HCC 上海皓元 was originally made mostly after hematoxylin and eosin (H&E) staining supplemented by routine histochemical stains such as Gomori staining for reticulin, Perls’ staining for iron, and Masson trichrome staining. All the slides were preliminary revised by two expert pathologists (M.R.

and L.D.T.), and the diagnosis of HCC was confirmed after accurate morphological analysis in all cases. HCC grading was based on the available material according to Edmondson and Steiner,18 and cases were divided into two groups: well-differentiated histology (G1) and moderately to poorly differentiated histology (G2/G3). The main pathological criteria for identifying well-differentiated HCCs and distinguishing them from high-grade dysplastic nodules (HGDNs) are reported in Supporting Table 1. The series included only cases with a tumor core and material available for immunocytochemical analyses (at least five recuts from the original block). Figure 1 shows a paradigmatic G1 HCC with an extralesional sample, which well represents the material under study.