The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy

Sugihara, Shigetaka; Nakashima, Osamu; Kojiro, Masamichi; Matsumoto, Yasuo; Tanaka, Masafoshi; Tanikawa, Kyuichi

doi:10.1002/1097-0142(19920915)70:6<1488::aid-cncr2820700607>3.0.co;2-j

Cited by 90 publications

(41 citation statements)

References 9 publications

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“…It is known that early hepatocellular carcinoma (HCC) is usually a well-differentiated carcinoma and then gradually changes into a moderately differentiated and poorly differentiated phenotype during tumor progression (Sugihara et al, 1992). GCIP expression was also detected in human liver tumor samples with immunostaining by specific anti GCIP antibody.…”

Section: Discussionsupporting

confidence: 87%

Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis

Xia

Stafford

et al. 2006

Oncogene

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Transcription factors with helix-loop-helix (HLH) motif play critical roles in controlling the expression of genes involved in lineage commitment, cell fate determination, proliferation, and tumorigenesis. To examine whether the newly identified HLH protein GCIP/CCNDBP1 modulates cell fate determination and plays a role in hepatocyte growth, proliferation, and hepatocarcinogenesis, we generated transgenic mice with human GCIP gene driven by a liver-specific albumin promoter. We demonstrated that in GCIP transgenic mice, the overall liver growth and regeneration occurred normally after liver injury induced by carbon tetrachloride (CCl 4 ). In the diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis, we demonstrated that overexpression of GCIP in mouse liver suppressed DEN-induced hepatocarcinogenesis at an early stage of tumor development. The number of hepatic adenomas at 24 weeks was significantly lower or not detected in GCIP transgenic male mice compared to the control mice under the same treatment. Although GCIP has little inhibition on the number of hepatic tumors at later stages (40 weeks), hepatocellular tumors in GCIP transgenic mice are smaller and well-differentiated compared to the poorly differentiated tumors in wildtype mice. Furthermore, we demonstrate that GCIP functions as a transcriptional suppressor, regulates the expression of cyclin D1, and inhibits anchorage-independent cell growth and colony formation in HepG2 cells, suggesting a significant role of GCIP in tumor initiation and development.

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Section: Discussionsupporting

confidence: 87%

Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis

Xia

Stafford

et al. 2006

Oncogene

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“…Remarkably, the progression from well to less differentiated HCC is seen in the majority of cases in our study. Similar findings have been reported in histological specimens with dedifferentiation of well differentiated HCC in Ϸ50% of cases (22) and in 75% of patients within 7-34 months being reported in a follow-up study (23).…”

Section: Discussionmentioning

confidence: 96%

Induction of aneuploidy by increasing chromosomal instability during dedifferentiation of hepatocellular carcinoma

Wilkens¹,

Flemming²,

Gebel³

et al. 2004

Pathology - Research and Practice

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To gain more insight into the role of chromosomal instability (CIN), the cytogenetic hallmark of most solid tumors, we performed fluorescence in situ hybridization (FISH) on interphase nuclei of cytological specimens enabling the correct detection of chromosome copies in intact tumor cells of 18 well (G1), moderately (G2), or poorly (G3) differentiated hepatocellular carcinomas (HCCs). A close correlation between the morphological dedifferentiation and increasing copy numbers and variation of FISH signals was seen for chromosomes 1 and 8, respectively (P < 0.0002). Four HCC G1 had constant chromosome patterns for chromosomes 1 and͞or 8 with a mean of signals per nucleus <5.08 and <3 different signal combinations, indicating a low level of CIN, as confirmed by FISH using probes for centromeres of chromosomes 3, 7, and 17. In contrast to this, five HCC G2-3 revealed >8.46 signals per nucleus and 23-41 different signal combinations, indicating high levels of CIN. In the remaining cases, signal counts from 5.96 -8.46 and 7-15 combinations were seen. Here, nuclei with constant aberration patterns and low copy numbers occurred alongside nuclei with inconstant patterns and high copy numbers. It is evident that in these cases a transition from well to moderately differentiated HCC developed in parallel to an increase in CIN, possibly induced by a major dysregulation of mitotic control mechanisms. In conclusion, CIN may induce a stepwise increase of aneuploidy in HCC that is mirrored by the morphological dedifferentiation of tumor cells.

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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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The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy

Cited by 90 publications

References 9 publications

Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis

Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis

Induction of aneuploidy by increasing chromosomal instability during dedifferentiation of hepatocellular carcinoma

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

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