Assessment of a HER2 scoring system for colorectal cancer: results from a validation study.

We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrollment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification.

Facing the enigma of the vascular network in hepatocellular carcinomas in cirrhotic and non-cirrhotic livers.

Aims: In this paper we aimed to analyse the typology and the phenotype of the different vascular modifications in human hepatocellular carcinomas (HCCs) with a new immunomorphological and gene expression approach. We also attempted to correlate these modifications with the histological parameters of tumour aggressiveness and the surrounding liver parenchyma.

Methods: Ninety-six HCCs (from 80 patients) were retrospectively enrolled, 46 occurring in non-cirrhotic livers, and 50 in livers transplanted for cirrhosis.

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation.

Aim: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification.

Methods: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected.

Adenocarcinoma in Crohn's disease: the pathologist's experience in a tertiary referral centre of inflammatory bowel disease.

The aim of the present study is to describe the histological and mutational characteristics of a series of both large and small bowel adenocarcinomas in patients with Crohn's disease from a tertiary referral centre of inflammatory bowel disease. Bowel adenocarcinoma was diagnosed in 11 (1.7%) of 660 consecutive patients submitted to surgery for histologically proven Crohn's disease in 5 years.

Histopathological evaluation of recurrent hepatitis C after liver transplantation: a review.

Although the morphological features of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) have been well established in the last decades, the differential diagnosis still represents a challenge for the pathologist, especially early recurrent hepatitis C vs mild acute cellular rejection. The present review focuses on the role of the pathologist and the pathology laboratory in the management of recipients with recurrent hepatitis C, the usefulness of early and late post-OLT liver biopsies, and the potential role of ancillary techniques (immunohistochemistry and reverse transcription-polymerase chain reaction, RT-PCR). The English literature on the topic is reviewed, focusing on the histopathology, the immunohistochemistry and the use of RT-PCR on HCV-positive post-OLT biopsies.

The meaning of tissue and serum HCV RNA quantitation in hepatitis C recurrence after liver transplantation: a retrospective study.

Background: While the role of serum HCV RNA quantitation in hepatitis C virus recurrence after liver transplantation is well established, the meaning of HCV RNA tissue quantitation is largely unclear, and no correlations with recipient outcome have been investigated yet.

Aims: To assess the predictive value, and a possible prognostic role, of tissue and serum HCV RNA in first post-transplant biopsies.

Methods: We retrospectively reviewed the first post-transplant biopsies of 83 recipients.

The use of neoplastic donors to increase the donor pool.

The aim of the study was to evaluate the experience of the Centre-Sud Transplant Organization (OCST) area using cadaveric donor with neoplastic diseases to evaluate the possibility of transmission to recipients. From January 1, 2003, to December 31, 2010, the neoplastic risk has been reported to be 5.4% (377/4654 referred donors).

OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation.

The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19.

Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy.

The purpose of the study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS-biopsy) performed on regions with abnormal MRI and/or MRSI for both the transition (TZ) and the peripheral (PZ) zones in patients with suspected prostate cancer with prior negative biopsy, and to analyze the relationship between MRSI and histopathological findings. MRI and MRSI were performed in 54 patients (mean age: 63.9 years, mean PSA value: 11.

Expanding the criteria of organ procurement from donors with prostate cancer: the application of the new Italian guidelines.

Prostate cancer (CaP) represents the most prevalent malignancy in men more than 60-year-old, posing a problem in organ procurement from elderly subjects. However, most of the currently diagnosed CaP are low-grade and intraprostatic, with low metastatic risk, and there is recent evidence that most patients are overdiagnosed. The Italian National guidelines about organ acceptance from neoplastic donors changed in March 2005, extending the pool of potential candidates with CaP and introducing the function of a second opinion expert.

Studies on immunoproteasome in human liver. Part I: absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis.

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive (alpha4 and beta1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28alphabeta regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis).

Preoperative prediction of hepatocellular carcinoma tumour grade and micro-vascular invasion by means of artificial neural network: a pilot study.

Background & Aims: Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables.

Methods: Clinical, radiological, and histological data from 250 cirrhotic patients resected (n=200) or transplanted (n=50) for HCC were analyzed.

Predictive value of frozen-section analysis in the histological assessment of steatosis before liver transplantation.

Histological quality assessment of donated livers is a key factor for extending the cadaveric donor pool for liver transplantation. We retrospectively compared frozen-section analysis with routine histological permanent slides and the outcomes of grafts in liver biopsies from 294 candidate donors. The kappa concordance coefficient of agreement between frozen-section analysis and routine histological analysis was very good for macrosteatosis (kappa = 0.

Real-time quantitative assay for routine testing of HCV RNA in formalin-fixed, paraffin-embedded liver samples.

The assessment of hepatitis C virus (HCV) RNA in liver tissues is clinically relevant in cases where histology, liver function tests, and HCV serology are not sufficient for a definitive diagnosis of HCV-related hepatitis. We analyzed 215 formalin-fixed, paraffin-embedded liver needle biopsies from patients infected with HCV genotypes 1b and 2. HCV RNA extracted from paraffin sections were quantified by means of a TaqMan real-time reverse transcription-polymerase chain reaction method.

EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.

A fusion gene, echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation.

Blood monitoring of granzyme B and perforin expression after intestinal transplantation: considerations on clinical relevance.

Background: The use of biomarkers for rejection monitoring represents a major goal in intestinal transplantation. We analyzed the blood expression of Granzyme B (GB) and Perforin (PF) in the following pathological conditions after intestinal transplantation: acute rejection (AR), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). The diagnostic accuracy and the clinical utility of these tests are finally discussed.

Clinical trial: peg-interferon alfa-2b and ribavirin for the treatment of genotype-1 hepatitis C recurrence after liver transplantation.

Background: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates.

Aim: To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response.

Methods: Fifty-three patients with post-LT HCV recurrence were enrolled.

The Italian multiorgan donor cancer screening protocol: 2002-2005 experience.

Background: We describe the results of the application of the Italian donor cancer screening protocol to all the 7608 candidate multiorgan donors presented in Italy in 2002-2005.

Methods: All suspect findings raised in the two presurgical and surgical phases of the protocol were investigated by extemporary pathologic evaluation. Donors were classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies).

Quality and safety in the Italian donor evaluation process.

Background: The shortage of available organs, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors. In this context the risk of donor-recipient transmission of infectious or neoplastic pathologies may be considered as a major issue; in each case for each organ potentially available, acceptable quality must be provided and unacceptable risks must be avoided.

Methods: We are presenting here the process of risk management followed by the Italian centers.

11C-choline positron emission tomography/computerized tomography for preoperative lymph-node staging in intermediate-risk and high-risk prostate cancer: comparison with clinical staging nomograms.

Background: Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa).

Objectives: To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms.

Design, Setting, And Participants: From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres.

Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer.

To analyze the potential diagnostic relevance of free plasma DNA (FPDNA), we enrolled 64 patients with localized prostate cancer (CaP). FPDNA was quantified by real-time polymerase chain reaction assessment of the HTERT gene in blood samples from 64 patients with CaP and 45 healthy males. Methylation of the GSTP1 gene was used to confirm the neoplastic origin of FPDNA in selected cases.

Real time RT-PCR approach for the evaluation of ERBB2 overexpression in breast cancer archival samples: a comparative study with FISH, SISH, and immunohistochemistry.

We tested the reliability of real time reverse transcription polymerase chain reactions as an alternative method for the assessment of ERBB2 status in paraffin-embedded tissues of 83 patients with breast cancer and 20 non-neoplastic controls. PCR was also compared with the immunohistochemical (IHC) HercepTest score and with fluorescence (FISH) and silver (SISH) in-situ hybridization, in 42 selected cases. ERBB2 mRNA was overexpressed in 26/83 (31%) breast cancer samples, using a cutoff calculated as the mean value of the controls plus 3 SD or with the receiver operating curve.

Tissue hepatitis C virus RNA quantification and protein expression help identify early hepatitis C virus recurrence after liver transplantation.

We compared tissue hepatitis C virus (HCV) RNA polymerase chain reaction quantification and HCV immunohistochemistry (IHC) to histology in biopsy tissues in order to differentiate between acute rejection and HCV hepatitis recurrence early after orthotopic liver transplantation (OLT). We analyzed the first biopsy performed because of alteration of serum aminotransferases in 65 consecutive OLT patients with HCV genotype 1b. In the histological analysis, we quantified the portal tracts, Councilman bodies, Councilman body/portal tract (CP) ratio, steatosis, and Knodell and Ishak scores.