Sabato 27 ottobre 2012 - Pacini Editore

COmuNiCaziONi ORali
complications. Up till now no histological characteristic has
been shown to correlate with the clinical severity of disease.
Currently the best predictive association with severity is HVPG.
Recently, histological parameters have been evaluated. Analysis
of nodule diameter and septal thickness has been shown
to correlate with HVPG (Sethasine et al.) 2 as has the digital
morphometric quantitation of collagen with the demonstration
of Collagen Proportionate Area (CPA) by using computer assisted
digital image analysis of picroSirius red stained sections
(Calvaruso et al.)
3 4.
The aim of this study is to compare proposed histological subclassifications
of cirrhosis, as suggested by several groups in the
Literature (Sethasine et al, Nagula et al, Kumar et al and Kim et
al.) 2 5 6 7 and to define which histological parameters, including
CPA, are able to correlate with the clinical evolution of cirrhosis
and above all which have good inter and intra observer reproducibility.
Methods. From a case series of 159 cirrhotic patients with liver
biopsies performed at the Royal Free Hospital in London, from
January 2003 to December 2007, 69 biopsies were analyzed (aetiology
was as follows: alcoholic liver disease - 38%, HCV - 27%,
cryptogenic - 13% and other causes - 22%). Exclusion criteria
were biopsies length (≤ 10mm) and excessive tissue fragmentation.
Fifty-three patients were clinically followed up for a mean of 46
months. For each biopsy the following were evaluated: Laennec
scoring system, number and size of cirrhotic nodules, fibrous
septa thickness and CPA (using picroSirius red stain). Statistical
analysis (t-test or Kruskall-Wallis test; cox regression analysis
for future decompensation evaluation) was performed to identify
which parameter correlated with decompensation. Intra/interobserver
agreement was performed by repeating evaluation on 20
biopsies and calculating concordance coefficients.
Results. Out of the 69 patients evaluated, 44 were compensated
at time of biopsy (group 1) while 25 were decompensated (group
2). Eleven patients from group 1, decompensated during follow
up. Out of all of the histological parameters evaluated, nodule
size (p = 0.001), septal width (p = 0.019) and CPA (p < 0.001)
were statistically correlated with decompensation at the time of
biopsy while only CPA was significantly associated with future
decompensation (OR 1.117, 95%CI 1.032-1.210, p = 0.006).
CPA was also the only variable with high intra and interobserver
concordance (0.98).
Conclusion. Histological characteristics such as nodule size, septal
width and CPA are associated with future clinical decompensation.
CPA was better than nodule/septa assessment and was the
only independently associated factor for future decompensation.
In addition CPA was the most reproducible parameter. Thus CPA
has predictive power and could be used to sub-classify cirrhosis,
identify patients who are at a greater risk of decompensation.
references
1 Anthony PP, Ishak KG, Nayak NC, et al. The morphology of cirrhosis:
definition, nomenclature and classification. Bulletin of the World
Health Organisarion 1977;55:521-4.
2 Sethasine S, Jain D, Groszmann RJ et al. Quantitative Histological-Hemodynamic
Correlations in Cirrhosis. Hepatology
2012;55:1146-53.
3 Calvaruso V, Dhillon AP, Tsochatzis E, et al. Proportionate Area predicts
decompensation in patients with recurrent HCV cirrhosis after
liver transplantation. J Gastroenterol Hepatol 2012.2
4 Calvaruso V, Burroughs AK, Standish R, et al. Computer-assisted
image analysis of liver collagen: relationship to Ishak scoring and
hepatic venous pressure gradient. Hepatology 2009;49:1236-44.
5 Nagula S, Jain D, Groszmann RJ, et al. Histological-hemodynamic
correlation in cirrhosis-a histological classification of the severity of
cirrhosis. J Hepatol 2006;44:111-7.
6 Kumar M, Sakhuja P, Kumar A, et al. Histological subclassification
of cirrhosis based on histological haemodynamic correlation. Aliment
Pharmacol Ther 2008;27:771-9.
283
7 Kim MY, Cho MY, Baik SK, et al. Histological subclassification of
cirrhosis using the Laennec fibrosis scoring system correlates with
clinical stage and grade of portal hypertension. Journal of Hepatology
2011;24.
hErG1 as a novel biomarker in pancreatic cancer
M. Callea3 , A. Arcangeli1 , E. Lastraioli1 , A. Sette1 , G. Perrone3 ,
D. Borzomati4 , F. Di Costanzo2 , R. Coppola4 , A. Onetti Muda3 1 Department of Experimental Pathology and Oncology, University of Florence;
2 Medical Oncology, Azienda Ospedaliero-Universitaria Careggi,
Florence, 3 Anatomical Pathology and 4 General Surgery Unit, Campus
Bio-Medico University of Rome, Rome, Italy
Introduction. Mounting evidence indicates that Ion Channels
and Transporters (ICT) are expressed aberrantly in cancer and
underlie many of the hallmarks of cancer. Proving their therapeutic
potential, treatments targeting Cl- channels and carbonic
anhydrase IX have successfully entered phase II clinical trials
in brain and kidney cancer. Thus, proteins involved in membrane
transport, long known as important drug targets in other
diseases (channelopathies), are a new class of therapeutic and/or
diagnostic targets in oncology. Several studies demonstrated that
the ether a- gò gò-related gene (hERG1) potassium channels is
expressed in several types of human cancers. hERG1 has a pleiotropic
regulatory effect on cancer (cell proliferation, survival,
invasiveness and angiogenesis). Finally, hERG1 is emerging as a
novel prognostic marker in acute leukemias and GI tract cancer.
Here we report the preliminary results of hERG1 expression in
pancreatic ductal adenocarcinoma (PDAC).
Materials and methods. Immunohistochemical staining for
hERG1 was performed using a monoclonal anti-hERG1 antibody
on formalin-fixed pancreatic TMA sections. A total of 44 PDAC
patients were evaluated (median age: 65 aa; M:24; F:20), consecutively
collected at the Campus Bio-Medico University from
March 2007 to March 2010; in each case, two 1.2 mm-diameter
cores were punched in a predefined tumor region and two additional
cores were taken from an adjacent non-neoplastic area.
A minimum of two-year f-up was available in all cases. hERG1
immunostaining was evaluated on the basis of a semiquantitative
score system taking into account percentage and staining intensity
of tumor cells.
Results. hERG1 specific immunostaining was observed in Langherans
islets, mainly attributable to the expression in beta cells,
whereas no expression was detected in normal pancreatic parenchyma.
Interestingly, a moderate to intense signal was observed
in over 50% of tumor cells of 26/44 PDAC. The median overall
survival in hEGR1 positive patients was 18 months (IQR 7-35),
significantly shorter than in in patients without hERG1 protein
expression (39 months, IQR 24-83) (p = 0.05).
Conclusion. Our preliminary results suggest that hERG1 might
represent a novel prognostic marker and a potential target for
therapy in PDAC.
The new fully automated system for Ki67
evaluation in assessing tumor grade in pancreatic
neuroendocrine tumors (PnETs)
D. Campani1 , N. Funel1 , P. Faviana1 , L.U. Pollina1 , M. Denaro1 ,
N. De Lio2 , V. Perrone2 , U. Boggi2 , F. Basolo1 1 Unit of Pathologic Anatomy, Department of Surgery, University of Pisa,
Pisa; 2 Unit of General and Transplant Surgery, Department of Oncology,
Pisa
Introduction. Neuroendocrine Tumors (NETs) are diseases with
varying degrees of aggressiveness and differentiation. The international
guidelines drive the pathologist to assess histological
evaluation of differentiation and grade 1 . Differentiation refers
to the extent to wich the neoplastic cells resemble their non neoplastic
counterparts. Well differentiated gatro-enteropancreatic