DNA image cytometric analysis of macroregenerative nodules (adenomatous hyperplasia) of the liver: Evidence in support of their preneoplastic nature

Orsatti, Giulia; Theise, Neil D.; Thung, Swan N.; Paronetto, Fiorenzo

doi:10.1002/hep.1840170416

Cited by 38 publications

(31 citation statements)

References 28 publications

(19 reference statements)

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“…56 In addition, we found in this study that LCC is associated with a low proliferative activity nucleolar organizer regions 72,73 ) and a primarily diploid DNA distribution pattern, with aneuploidy tending to appear with detected by Ki-67 and PCNA immunostains, similar to that of quiescent liver, but shows a higher degree of apoptosis as greater histological atypia. 69,74,75 These considerations suggest a pathogenetic model (Fig. determined by the TUNEL assay, features that are consistent with terminally differentiating cells.…”

Section: Discussionmentioning

confidence: 89%

Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis

1997

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Liver cell dysplasia is the term originally applied by AnLarge cell change (LCC), characterized by cellular enthony et al. 1 in 1973 to cytologically atypical hepatocytes largement, nuclear pleomorphism and hyperchromasia, showing cellular enlargement, nuclear pleomorphism with and multinucleation of hepatocytes, is a common lesion hyperchromasia, and multinucleation. In their study, this in cirrhotic livers, but its nature, significance, and pathoalteration was uncommon in normal livers and occasionally genesis remain uncertain. Therefore, we assessed the noted in cirrhotic livers, particularly with chronic hepatitis prognostic value of LCC as a marker of subsequent hepato-B infection, but was most prevalent in cirrhotic livers bearing cellular carcinoma (HCC) through a case-control study hepatocellular carcinoma (HCC). Because of this relationthat compared pretransplant liver biopsy specimens from ship, liver cell dysplasia, later termed large cell dysplasia, 37 cirrhotic liver transplant recipients with HCC to speciwas proposed to represent a premalignant change.1 mens from a control group of recipients without HCC, Over the succeeding 25 years, however, this proposal has matched for sex, age ({5 years), and cause of cirrhosis.been contested, and other workers have concluded that large LCC was identified in 16 (43%) of the study and 7 (19%) cell dysplasia instead represents a regenerative or degeneraof the control group biopsy specimens. By matched-pair tive phenomenon. Evidence has been marshalled to support analysis, LCC conveyed a moderately increased risk of both sides of this controversy, but much of the data are later HCC with an estimated odds ratio of 3.3 (95% CI, conflicting or circumstantial in nature, and no consensus has 1.2-15; P Å .038). However, a pathology review of 45 been reached as to the nature or significance of the alteration. HCCs showed adjoining LCC in only 12 (27%) and didBecause of this lingering uncertainty, the pathogenetically not suggest a morphological transition or a histogenetic noncommittal term large cell change (LCC) is now recomassociation between the two lesions. LCC hepatocytes dismended as an alternative designation.2 played a low proliferative rate by Ki-67 or proliferating The controversy over LCC poses a practical conundrum: cell nuclear antigen immunostaining (labeling indices of Should it receive special notice as a potential precursor of 0.27 and 0.73) but showed a greater degree of apoptosis malignancy, or should it be dismissed as an inconsequential than normal hepatocytes (labeling indices of 1.9 and 0.23; marker of chronic liver injury? To address this issue, we P Å .03) To reconcile these findings, we propose that LCC evaluated three different aspects of LCC. First, we performed derives from derangements in the hepatocyte's normal a case-control study to evaluate whether the presence of LCC process of polyploidization. Such derangements, possibly presaged any increased risk for the subsequent presence of caused by chronic inflammation-induced DNA damage, HCC...

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Section: Discussionmentioning

confidence: 89%

Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis

1997

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“…Hepatocellular dysplastic nodules are considered HCC precursors and are currently classified into low-grade (LGDN) and high-grade (HGDN) categories. 1 Their premalignant nature was inferred by a number of features such as morphology, 2-4 proliferative activity, 5,6 vascular pattern, 7 DNA content, 8 and clonality. [9][10][11] However, their biological properties are still unknown, and it has been repeatedly emphasized that the classification of hepatocellular nodules should be supported by genetic data to be diagnostically and prognostically helpful.…”

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confidence: 99%

Molecular Changes in Hepatocellular Dysplastic Nodules on Microdissected Liver Biopsies

et al. 2000

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The genetic profile of dysplastic hepatocellular nodules arising in cirrhosis is poorly understood. We assessed loss of heterozygosity (LOH) and microsatellite instability (MI) in 10 dysplastic nodules (4 low-grade and 6 high-grade) with surrounding cirrhosis and in 10 hepatocellular carcinomas (HCC). Six microsatellite loci were selected and investigated on microdissected needle biopsies. Twenty-four (24.4%) informative loci showed allelic loss, while MI was seen in 3 loci only (3%). The most involved sites were located on chromosomes 4q (54.5%) and 8p (50%). LOH was documented in 16.6%, cirrhotic, 50% low-grade dysplastic nodules (LGDN), 83% high-grade dysplastic nodules (HGDN), and 70% malignant nodules. LOH at multiple loci was increasingly seen from cirrhotic to HGDN, but not from the latter to HCC. The fractional allelic loss (FAL) was significantly increased in dysplastic and neoplastic nodules as compared with cirrhosis (P < .01). The progressive accumulation of genetic changes in cirrhotic, dysplastic, and malignant hepatocellular nodules is in keeping with a multistep process of carcinogenesis; within this spectrum, HGDN can be considered advanced precursors of HCC. (HEPATOLOGY 2000;32:942-946.)

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“…HCC generally develops in the setting of chronic hepatitis or cirrhosis in which there is continuous inflammation and regeneration of hepatocytes ( Figure 1). Hepatocarcinogenesis may begin in preneoplastic lesions such as macroregenerative nodules, low-grade and high grade dysplastic nodules (Takayama et al, 1990;Orsatti et al, 1993). Accelerated proliferation of hepatocytes and development of monoclonal hepatocyte populations occur in all preneoplastic conditions.…”

Section: Sequential Changes In the Liver Leading To Hccmentioning

confidence: 99%

Mechanisms of hepatocarcinogenesis

Lemoine¹,

Saffroy²,

Debuire³

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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DNA image cytometric analysis of macroregenerative nodules (adenomatous hyperplasia) of the liver: Evidence in support of their preneoplastic nature

Cited by 38 publications

References 28 publications

Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis

Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: Matched case-control study, pathological analysis, and pathogenetic hypothesis

Molecular Changes in Hepatocellular Dysplastic Nodules on Microdissected Liver Biopsies

Mechanisms of hepatocarcinogenesis

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