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Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications

Kirimlioglu, H and Dvorchick, I and Ruppert, K and Finkelstein, S and Marsh, JW and Iwatsuki, S and Bonham, A and Carr, B and Nalesnik, M and Michalopoulos, G and Starzl, T and Fung, J and Demetris, A (2001) Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: Biologic and therapeutic implications. Hepatology, 34 (3). 502 - 510. ISSN 0270-9139

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The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (< 15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kirimlioglu, H
Dvorchick, I
Ruppert, Kruppertk@pitt.eduRUPPERTK
Finkelstein, S
Marsh, JW
Iwatsuki, S
Bonham, A
Carr, B
Nalesnik, Mnalesnik@pitt.eduNALESNIK
Michalopoulos, G
Starzl, Ttes11@pitt.eduTES11
Fung, J
Demetris, A
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 2001
Date Type: Publication
Journal or Publication Title: Hepatology
Volume: 34
Number: 3
Page Range: 502 - 510
DOI or Unique Handle: 10.1053/jhep.2001.26633
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0270-9139
Other ID: uls-drl:31735062120690, Starzl CV No. 2163
Date Deposited: 08 Apr 2010 17:37
Last Modified: 02 Feb 2019 15:55


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