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Apoptosis versus cytoproliferation in hepatocellular carcinoma: role of protein oxidation
Category 4: Hepatocellular
carcinoma,
expression profiling demonstrates, for the first time, broad and fundamental differences in pathogenic mechanisms of hepatitis B versus C induced HCC. These studies will aid in developing specific tumor markers and targeted therapies for HCC and identify candidate genes for genome-wide susceptibility gene searches.
I
287
HEMANGIOMA-LIKE LESIONS IN PATIENTS WITH CHRONIC LIVER DISEASE: DIAGNOSTIC EVALUATION
E. Caturelli, M. Pompili. D.A. Siena, A. Andriulli, M. Bisceglia. U.O. Gastroenterologia, Ospetie “Casa Sollievo della Sofferenza” WCCS, Cattedra di Medicina Interna II, Universitd Cattolica de1 Sacro Cuore, Roma; V.O. Gastroenterologia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg); U.O. Gastroenterologia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg); Servizio Anatomia e Istologia Patologica gia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg), Italy Purpose:
To quantify the risk of misdiagnosis of focal hepatic lesions presenting on ultrasonography (US) as “typical hemangiomas” in a population at high risk for HCC and to identify the most effective approach to their differential diagnosis. Materials and Methods 1982 newly diagnosed cirrhotics underwent US and serum alpha fetoprotein (AFP) studies for early HCC detection. Focal lesions with typical features of hemangioma were subjected to confirmatory contrast-enhanced dynamic or spiral computed tomography (CT) and/or technetium 99m-labeled red blood cell single photon emission CT and (in the absence of image confirmation) US-guided fine-needle biopsy. Patients whose initial scan revealed no lesions or lesions diagnosed as hemangiomas were enrolled in an US follow-up program. All hemangioma-like lesions emerged during follow-up were studied as described above or (during the last 3 years of the study) biopsied directly. Results: Initial US revealed hemangioma-like lesions in 44 out of 1982 patients: 22 were hemangiomas, and 22 were HCC. The 26 hemangioma-like lesions detected during me follow-up of 1648 patients were 22 HCC and 4 dysplastic nodules. No patient with hemangioma-like lesion presented elevated AFP serum levels. Conclusions: If the initial US examination of a cirrhotic liver reveals a “typical hemangioma”, confirmatory imaging studies are necessary since 50% (in our study) will be hyperechoic HCCs. The probability of HCC (or preneoplastic lesions) is virtually 100% for hemangioma-like lesions detected on US along the follow-up program. US-guided biopsy can be safely performed to confirm the diagnosis. Diagnostic AFP serum levels are not found in patients with hyperechoic HCC.
I 288
DIAGNOSIS OF LIVER NODULES OBSERVED IN CIRRHOTICS DURING ULTRASOUND SCREENING FOR EARLY DETECTION OF HEPATOCELLULAR CARCINOMA
E. Caturelli, D.A. Siena, M. Vigliotti, V. Attino, M. Bisceglia, A. Andriulli. U.O. Gastroenterologia.. U.O. Ematologia., Servizio Anatomia E Istologia Patologica., Servizio Anatomia E Istologia Patologica., U.O. Gastroenterologia, Italy Purpose: To evaluate the nature of focal liver lesions detected during the ultrasound follow-up of a cirrhotic (prevalently anti-HCV positive) population. Materials and Methods: The study population consisted in 1827 consecutive newly diagnosed cirrhotic patients without liver nodules at enrollment. Patients were screened at 4-month intervals by ultrasound (US) and serum alpha fetoprotein (AFP) assessment. All lesions detected on imaging studies (except those accompanied by significantly elevated AFP levels and those with hyperechoic appearance) were subjected to biopsy (histology and cytology).
liver regeneration,
apoptosis
95
Results: During the 7-year follow-up period (mean 43.1 months), one or more solid focal lesions were found in 287 patients. AFP was diagnostic for hepatocellular carcinoma (HCC) in 51 patients. US-guided fine-needle biopsy was performed in the remaining 236 patients, yielding a diagnosis in 214: 198 HCC, 11 adenomatous hyperplasias, and five B cell non-Hodgkin lymphomas (all confined to the liver and all in patients with HCV-related disease). Twenty-two patients with non-diagnostic biopsies received diagnoses of HCC (20) or adenomatous hyperplasia (2) based on arteriography or surgical biopsy. Conclusions: Focal lesions arising in patients with HCV-related liver cirrhosis can be other than HCC, and US-guided fine-needle biopsy plays an important role in their diagnosis. The prevalence of non-Hodgkin lymphoma in this selected population was 0.31%. The fact that all five lymphoma patients had cirrhosis related to hepatitis C strengthens the hypothesis of an etiologic correlation between the latter infection and B cell lymphoproliferative disorders.
I 289
APOPTOSIS VERSUS CYTOPROLIFERATION IN HEPATOCELLULAR CARCINOMA: ROLE OF PROTEIN OXIDATION
E.H. Ibrahim, H.A. El-Aggan, S.A. Mahmoud, L.K. Younis. Epatobiliary Unit, Department of Medicine, Faculty of Medicine, University of Alexandria, Egypt
Objective: Neoplastic growth is determined by the balance between cell death and cell proliferation, the present study was designed to study the rates of apoptosis and proliferation in hepatocellular carcinoma (HCC) in relation to tumor growth and protein oxidation. Methods: Fifty patients with cirrhosis (30 with histologically-proven HCC and 20 without HCC) were included in the study. In HCC patients, core liver biopsies were analyzed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling method and for ~53 expression by immunohistochemistry. The proliferative activity of HCC was assessed using proliferating cell nuclear antigen labeling. In all patients, the plasma levels of carbonyl proteins and advanced oxidation protein products, markers of protein oxidation, and plasma xanthine oxidase activity were determined. Results: In HCC, both the apoptotic rate and the proliferative activity increased with decreased tumor differentiation and with increasing tumor size and stage @ < 0.01). A positive correlation was found between the proliferative activity and both the apoptotic rate and ~53 expression @ < 0.01). However, the apoptotic rate was always less than the proliferative activity and their ratio tended to decrease in higher tumor grade, size and stage and in p53positive tumors @ 5 0.001). Meanwhile, The plasma oxidized proteins levels and the plasma xanthine oxidase activity showed a significant stepwise increase in cirrhotic patients without HCC and with the subsequent development of HCC (p < 0.0001). The markers of protein oxidation in HCC patients had positive correlations with the proliferative activity and inverse correlations with the ratio between the apoptotic rate and the proliferative activity @ < 0.05), but showed no significant correlation with the apoptotic rate @ < 0.05). Conclusions: Cell proliferation predominates over apoptosis during HCC progression coincident with expression of mutant ~53 and an enhanced protein oxidation. Also, oxidative stress seems to play a role in the progress of liver cirrhosis to HCC
I 294
ANGIOGENIN IN HEPATOCELLULAR CARCINOMA: CORRELATION WlTH TUMOR VASCULARITY AND PROLIFERATIVE ACTIVITY
H.A. El Aggan, S.E. Hegab, N.M. Baddour, A.F. Ketat. Hepatobiliary Unit, Department of Medicine, Faculty of Medicine, University of Alexandria, Egypt
Objective: Angiogenesis is an essential process for growth and metas-
carcinoma,
expression profiling demonstrates, for the first time, broad and fundamental differences in pathogenic mechanisms of hepatitis B versus C induced HCC. These studies will aid in developing specific tumor markers and targeted therapies for HCC and identify candidate genes for genome-wide susceptibility gene searches.
I
287
HEMANGIOMA-LIKE LESIONS IN PATIENTS WITH CHRONIC LIVER DISEASE: DIAGNOSTIC EVALUATION
E. Caturelli, M. Pompili. D.A. Siena, A. Andriulli, M. Bisceglia. U.O. Gastroenterologia, Ospetie “Casa Sollievo della Sofferenza” WCCS, Cattedra di Medicina Interna II, Universitd Cattolica de1 Sacro Cuore, Roma; V.O. Gastroenterologia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg); U.O. Gastroenterologia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg); Servizio Anatomia e Istologia Patologica gia, Ospedale “Casa Sollievo della Sofferenza” IRCCS, San Giovanni Rotondo (Fg), Italy Purpose:
To quantify the risk of misdiagnosis of focal hepatic lesions presenting on ultrasonography (US) as “typical hemangiomas” in a population at high risk for HCC and to identify the most effective approach to their differential diagnosis. Materials and Methods 1982 newly diagnosed cirrhotics underwent US and serum alpha fetoprotein (AFP) studies for early HCC detection. Focal lesions with typical features of hemangioma were subjected to confirmatory contrast-enhanced dynamic or spiral computed tomography (CT) and/or technetium 99m-labeled red blood cell single photon emission CT and (in the absence of image confirmation) US-guided fine-needle biopsy. Patients whose initial scan revealed no lesions or lesions diagnosed as hemangiomas were enrolled in an US follow-up program. All hemangioma-like lesions emerged during follow-up were studied as described above or (during the last 3 years of the study) biopsied directly. Results: Initial US revealed hemangioma-like lesions in 44 out of 1982 patients: 22 were hemangiomas, and 22 were HCC. The 26 hemangioma-like lesions detected during me follow-up of 1648 patients were 22 HCC and 4 dysplastic nodules. No patient with hemangioma-like lesion presented elevated AFP serum levels. Conclusions: If the initial US examination of a cirrhotic liver reveals a “typical hemangioma”, confirmatory imaging studies are necessary since 50% (in our study) will be hyperechoic HCCs. The probability of HCC (or preneoplastic lesions) is virtually 100% for hemangioma-like lesions detected on US along the follow-up program. US-guided biopsy can be safely performed to confirm the diagnosis. Diagnostic AFP serum levels are not found in patients with hyperechoic HCC.
I 288
DIAGNOSIS OF LIVER NODULES OBSERVED IN CIRRHOTICS DURING ULTRASOUND SCREENING FOR EARLY DETECTION OF HEPATOCELLULAR CARCINOMA
E. Caturelli, D.A. Siena, M. Vigliotti, V. Attino, M. Bisceglia, A. Andriulli. U.O. Gastroenterologia.. U.O. Ematologia., Servizio Anatomia E Istologia Patologica., Servizio Anatomia E Istologia Patologica., U.O. Gastroenterologia, Italy Purpose: To evaluate the nature of focal liver lesions detected during the ultrasound follow-up of a cirrhotic (prevalently anti-HCV positive) population. Materials and Methods: The study population consisted in 1827 consecutive newly diagnosed cirrhotic patients without liver nodules at enrollment. Patients were screened at 4-month intervals by ultrasound (US) and serum alpha fetoprotein (AFP) assessment. All lesions detected on imaging studies (except those accompanied by significantly elevated AFP levels and those with hyperechoic appearance) were subjected to biopsy (histology and cytology).
liver regeneration,
apoptosis
95
Results: During the 7-year follow-up period (mean 43.1 months), one or more solid focal lesions were found in 287 patients. AFP was diagnostic for hepatocellular carcinoma (HCC) in 51 patients. US-guided fine-needle biopsy was performed in the remaining 236 patients, yielding a diagnosis in 214: 198 HCC, 11 adenomatous hyperplasias, and five B cell non-Hodgkin lymphomas (all confined to the liver and all in patients with HCV-related disease). Twenty-two patients with non-diagnostic biopsies received diagnoses of HCC (20) or adenomatous hyperplasia (2) based on arteriography or surgical biopsy. Conclusions: Focal lesions arising in patients with HCV-related liver cirrhosis can be other than HCC, and US-guided fine-needle biopsy plays an important role in their diagnosis. The prevalence of non-Hodgkin lymphoma in this selected population was 0.31%. The fact that all five lymphoma patients had cirrhosis related to hepatitis C strengthens the hypothesis of an etiologic correlation between the latter infection and B cell lymphoproliferative disorders.
I 289
APOPTOSIS VERSUS CYTOPROLIFERATION IN HEPATOCELLULAR CARCINOMA: ROLE OF PROTEIN OXIDATION
E.H. Ibrahim, H.A. El-Aggan, S.A. Mahmoud, L.K. Younis. Epatobiliary Unit, Department of Medicine, Faculty of Medicine, University of Alexandria, Egypt
Objective: Neoplastic growth is determined by the balance between cell death and cell proliferation, the present study was designed to study the rates of apoptosis and proliferation in hepatocellular carcinoma (HCC) in relation to tumor growth and protein oxidation. Methods: Fifty patients with cirrhosis (30 with histologically-proven HCC and 20 without HCC) were included in the study. In HCC patients, core liver biopsies were analyzed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling method and for ~53 expression by immunohistochemistry. The proliferative activity of HCC was assessed using proliferating cell nuclear antigen labeling. In all patients, the plasma levels of carbonyl proteins and advanced oxidation protein products, markers of protein oxidation, and plasma xanthine oxidase activity were determined. Results: In HCC, both the apoptotic rate and the proliferative activity increased with decreased tumor differentiation and with increasing tumor size and stage @ < 0.01). A positive correlation was found between the proliferative activity and both the apoptotic rate and ~53 expression @ < 0.01). However, the apoptotic rate was always less than the proliferative activity and their ratio tended to decrease in higher tumor grade, size and stage and in p53positive tumors @ 5 0.001). Meanwhile, The plasma oxidized proteins levels and the plasma xanthine oxidase activity showed a significant stepwise increase in cirrhotic patients without HCC and with the subsequent development of HCC (p < 0.0001). The markers of protein oxidation in HCC patients had positive correlations with the proliferative activity and inverse correlations with the ratio between the apoptotic rate and the proliferative activity @ < 0.05), but showed no significant correlation with the apoptotic rate @ < 0.05). Conclusions: Cell proliferation predominates over apoptosis during HCC progression coincident with expression of mutant ~53 and an enhanced protein oxidation. Also, oxidative stress seems to play a role in the progress of liver cirrhosis to HCC
I 294
ANGIOGENIN IN HEPATOCELLULAR CARCINOMA: CORRELATION WlTH TUMOR VASCULARITY AND PROLIFERATIVE ACTIVITY
H.A. El Aggan, S.E. Hegab, N.M. Baddour, A.F. Ketat. Hepatobiliary Unit, Department of Medicine, Faculty of Medicine, University of Alexandria, Egypt
Objective: Angiogenesis is an essential process for growth and metas-