Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma
BCLC Group, Liver Unit, IMDM, Hospital Clínic, c/ Villarroel 170, Escala 11, 4° Planta, 08036 Barcelona, Spain Gut
(Impact Factor: 14.66).
01/2012; 61(10):1481-7. DOI: 10.1136/gutjnl-2011-301862
Conventional pathological analysis fails to achieve sufficient sensitivity and specificity for the diagnosis of hepatocellular carcinoma (HCC) in small nodules. Immunohistochemical staining for glypican 3 (GPC3), heat shock protein 70 (HSP70) and glutamine synthetase (GS) has been suggested to allow a confident diagnosis but no prospective study has established the diagnostic accuracy of this approach. The aim of this study is to assess prospectively the diagnostic accuracy of a panel of markers (GPC3, HSP70, GS) for the diagnosis of HCC in patients with cirrhosis with a small (5-20 mm) nodule detected by ultrasound screening.
Sixty patients with cirrhosis with a single nodule 5-20 mm newly detected by ultrasound were included in the study. Contrast-enhanced ultrasound, magnetic resonance and fine needle biopsy of the nodule (gold standard) were performed; the biopsy was repeated in case of diagnostic failures. Three consecutive sections of the first biopsy sample with meaningful material were stained with antibodies against GPC3, HSP70 and GS.
Forty patients were diagnosed with HCC. The sensitivity and specificity for HCC diagnosis were: GPC3 57.5% and 95%, HSP70 57.5% and 85%, GS 50% and 90%, respectively. The sensitivity and specificity of the different combinations were: GPC3+HSP70 40% and 100%; GPC3+GS 35% and 100%; HSP70+GS 35% and 100%; GPC3+HSP70+GS 25% and 100%. When at least two of the markers were positive (regardless of which), the sensitivity and specificity were 60% and 100%, respectively. Conventional pathological analysis yielded three false negative results, but the addition of this panel only correctly classified one of these cases as HCC.
These data within a prospective study establish the clinical usefulness of this panel of markers for the diagnosis of early HCC. However, the panel only slightly increases the diagnostic accuracy in an expert setting.
Available from: PubMed Central
- "Its expression was observed in 282 of 392 HCC cases (71.9%), whereas only 14 of 115 non-neoplastic liver tissues expressed HSP70 (P<0.001) (9). The sensitivity and specificity in detecting HCC were identified as 57.5 and 85%, respectively (10). Furthermore, the expression of HSP70 is correlated with differentiation and apoptosis of tumor cells. "
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ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. HCC affects approximately one million individuals annually worldwide, with the incidence equal to the mortality rate. In 2008, HCC was listed as the third most lethal cancer. Thus, early diagnosis is crucial for improving the survival rate for patients. α-fetoprotein (AFP) together with iconography and pathology detection are commonly used in the clinical early diagnosis of liver cancer. However, the specificity and sensitivity of AFP used in screening for liver cancer are not satisfactory. Athough the development of molecular biology has led to the identification of new tumor markers, including proteantigens, cytokines, enzymes and isoenzymes, as well as related genes that can be used in the treatment and prognosis of liver cancer, more tumor markers are required for effective early diagnosis of diseases and monitoring of the curative effect.
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ABSTRACT: Colorectal cancer is the second leading cause of cancer-related death. Prevention of this neoplasm should be achievable by screening programs in asymptomatic patients. The objective of the present paper is to assess colonoscopic findings in asymptomatic people submitted to screening.
A prospective study was undertaken on 153 consecutive asymptomatic people submitted to colonoscopy. Sex, age, previous diseases, and familial cases of cancer, as well as tobacco and alcohol ingestion were assessed. Patients with rectal macro- or microscopic bleeding and colorectal diseases were excluded. Bowel cleansing, polyps, angioectasias, diverticular disease, inflammation, and neoplasm were also verified. Polyps were classified according to their size, number, and location.
Colonoscopic alterations were detected in 99 individuals: polyps in 64.3 %, diverticular disease in 27.9 %, inflammatory mucosal alterations in 9.7 %, melanosis coli in 2.6 %, and angioectasias in 7.8 %. There was an increasing incidence of polyps in individuals older than 50 years. Multivariate logistic regression showed age and sex as predictive factors for polyps [odds ratio (OR) = 1.43; 1.19 < OR < 2.67].
The results of this investigation revealed a significant incidence of colonoscopic alterations in asymptomatic people submitted to colonoscopy for colorectal cancer screening.
Available from: Seon-Ah Ha
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