Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver

Arakawa, Masahiro; Kage, Masayoshi; Sugihara, Shigetaka; Nakashima, Toshiro; Suenaga, Masahiro; Okuda, Kunio

doi:10.1016/0016-5085(86)90458-0

Cited by 243 publications

(96 citation statements)

References 22 publications

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“…Evidence accumulated in the last two decades strongly favors the existence of a sequence of events in hepatic nodules that precedes the emergence of hepatocellular carcinoma (HCC), [1][2][3][4][5][6][7][8][9][10] and these lesions are recognized as precursors of HCC. However, from the beginning of their recognition, there has been considerable confusion concerning nomenclature and diagnostic approaches to these hepatic nodules.…”

mentioning

confidence: 99%

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

2008

Hepatology

721

240

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confidence: 99%

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

2008

Hepatology

721

240

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“…[32][33][34][35][36] The current study showed that nonneoplastic hepatocytes and well differentiated HCC (Edmondson-Steiner Grades I or II) were characterized by diffuse CEACAM1 expression. As the tumor progressed, poorly differentiated foci (Edmondson-Steiner Grades III or IV) with loss of CEACAM1 expression emerged within the background tumor tissue that had diffuse CEACAM1 expression.…”

Section: Discussionmentioning

confidence: 99%

Loss of carcinoembryonic antigen‐related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma

Cruz

Wakai

Shirai

et al. 2005

Cancer

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BACKGROUNDCarcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is a negative regulator of tumor cell growth, and may function as a tumor suppressor. CEACAM1 expression is down‐regulated with increasing histologic grade in a number of malignancies. The authors hypothesized that loss of CEACAM1 expression in hepatocellular carcinoma (HCC) cells may function as an adverse prognostic factor.METHODSA retrospective analysis was conducted of 139 consecutive patients who underwent resection for HCC, with a median follow‐up period of 83 months. Immunohistochemistry of the resected specimens was conducted using a monoclonal anti‐CEACAM1 antibody. CEACAM1 expression in HCC was classified into two categories: diffuse expression, characterized by positive staining throughout the tumor specimen, or loss of expression, in which there were distinct areas of negative staining within the tumor specimen.RESULTSOf the 139 patients, 113 were classified as having tumors with diffuse expression and 26 had loss‐of‐expression tumors. Loss of CEACAM1 expression was more frequent in tumor specimens with Edmondson–Steiner Grades III or IV (21 of 32 [66%]) than in tumor specimens with Grades I or II (5 of 107 [5%]; P < 0.001) and was always seen in areas with the highest histologic grade. Loss of CEACAM1 expression was significantly associated with large tumor size, multiplicity of the tumor, portal vein invasion, and satellite nodules and affected survival adversely, according to univariate (P < 0.0001) and multivariate analyses (relative risk, 5.737; P < 0.001).CONCLUSIONSLoss of CEACAM1 expression reflects aggressive tumor biology and thus indicates a poor prognosis for patients with HCC. Cancer 2005. © 2005 American Cancer Society.

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“…23 A subpopulation with a more malignant potential develops in the pre-existing nodule, suggesting that lessdifferentiated HCC occurs in well-differentiated HCC, and welldifferentiated HCC in turn results in atypical hyperplasia in a stepwise manner. 24 In reference to the incidence of tumor heterogeneity in small HCC, Kenmochi et al 25 reported 46.7% (7/15) in HCC smaller than 2 cm in diameter, and 36% (4/11) in HCC with 2-3 cm in diameter, Nakashima et al 26 reported that tumor heterogeneity occurred in 18.6% (16/86) of HCC smaller than 2 cm in diameter.…”

Section: Discussionmentioning

confidence: 99%

Tumor heterogeneity in small hepatocellular carcinoma: Analysis of tumor cell proliferation, expression and mutation of p53 AND ?-catenin

Matsuda

Fujii

et al. 2001

Int. J. Cancer

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Most hepatocellular carcinomas (HCCs) first occur as welldifferentiated HCCs, from which poorly differentiated HCC cells develop because of dedifferentiation. In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation-related genes p53 and ␤-catenin. Of 41 surgically resected small HCCs, 11 were identified to have tumor heterogeneity. DNA from the 11 small HCCs, consisting of 29 intratumoral lesions and 11 noncancerous liver tissues adjacent to HCCs, was extracted from paraffin embedded tissue sections. Exons 5-8 of p53 gene and exon 3 of ␤-catenin gene were amplified by polymerase chain reaction and analyzed by direct sequence. The serial sections were also immunostained by anti-Ki-67, p53 and ␤-catenin antibody. Immunohistochemistry showed that the p53 overexpression was significantly related to the proliferative activities as evaluated by Ki-67 immunostaining and to the histological differentiation. The expression of ␤-catenin was found to be heterogeneously distributed not only in various histological grades of the same tumor but also in areas of the same histological grade. p53 and ␤-catenin gene mutations were detected in 1 tumor respectively, both of which were second primary HCCs and also recurred later. The p53 mutation showed the same mutation pattern in heterogeneous subpopulations. ␤-catenin mutation was detected only in the less differentiated lesion but not in the well-differentiated lesion of tumor. In conclusion, our findings suggest that there was histological heterogeneity in small but established HCC, which was accompanied by increased proliferative activity and p53 overexpression. The overexpression of ␤-catenin may be related to the proliferative activity and dedifferentiation of HCC.

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Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver

Cited by 243 publications

References 22 publications

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

Loss of carcinoembryonic antigen‐related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma

Tumor heterogeneity in small hepatocellular carcinoma: Analysis of tumor cell proliferation, expression and mutation of p53 AND ?-catenin

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