Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas

Morimoto, Osakuni; Nagano, Hiroaki; Sakon, Masato; Fujiwara, Yoshiyuki; Yamada, Terumasa; Nakagawa, Hidewaki; Miyamoto, Atsushi; Kondo, Motoi; Arai, Isao; Yamamoto, Tameyoshi; Ôta, Hideo; Dono, Keizo; Umeshita, Koji; Nakamori, Shoji; Sasaki, Yo; Ishikawa, Osamu; Imaoka, Shingi; Monden, Morito

doi:10.1016/s0168-8278(03)00233-2

Cited by 108 publications

(80 citation statements)

References 28 publications

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“…Rather, expression levels of ZYX in patients with multiple tumor lesions were elevated when compared to cases with solitary tumor (B60-fold higher than solitary hepatocellular carcinoma). As many studies have shown that intrahepatic satellite nodules in hepatocellular carcinoma are mostly metastases of the primary lesion, 14,15 our finding may be interpreted as indicating a biological role for ZYX in hepatocellular carcinoma tumor cell disseminations. We have also shown ZYX overexpressions to ZYX is a zinc-binding phosphoprotein (B61 kd) that is characterized by three LIM domains.…”

Section: Discussionsupporting

confidence: 63%

Novel identification of zyxin upregulations in the motile phenotype of hepatocellular carcinoma

Lai

Pang

et al. 2006

Modern Pathology

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Genome-wide copy number aberrations are common in hepatocellular carcinoma, although the precise genetic events underlying disease progression remain poorly defined. Previous work from our group has indicated several regional chromosomal gains such as chromosome 7q34-q36 that are associated with advanced metastatic tumors. Although the distal chromosome 7q gains have also been implicated in the progression of other malignancies, information on underlying targeted genes is limited. In this study, we have examined the chromosome 7q34-q36 region for involved gene(s) (or genes of interest). An integrated array-based comparative genomic hybridization and transcriptional mapping analyses has enabled us to identify a single candidate, zyxin on chromosome 7q34-q36. This array-derived finding was supported by quantitative reverse transcription-polymerase chain reaction, which also indicated common upregulations of zyxin in hepatocellular carcinoma tumors compared to their corresponding nonmalignant liver tissue (17/52 cases; 33%). Although there was no correlation between zyxin expression and tumor stagings, there was a significant increase in messenger RNA levels in hepatocellular carcinoma cases that presented with multifocal disease (211.57936.9-fold) compared to those with solitary lesions (3.576.3-fold). Moreover, recurrence after resection was common in cases that displayed zyxin overexpressions in the initial resected tumor (P ¼ 0.05). Functional examination of zyxin by small interfering RNA-mediated knockdown in Hep3B cell line indicated a significant inhibition on cell migration through porous membrane (P ¼ 0.002) and invasion through matrigel-coated membrane (P ¼ 0.005). In summary, mapping of chromosome 7q34-q36 has led to the identification of frequent zyxin overexpressions in hepatocellular carcinoma, and a potential role for zyxin in conferring a motile phenotype.

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Section: Discussionsupporting

confidence: 63%

Novel identification of zyxin upregulations in the motile phenotype of hepatocellular carcinoma

Lai

Pang

et al. 2006

Modern Pathology

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“…HCC recurrence derives from both residual intrahepatic metastasis (IM) and multicentric carcinogenesis (MC). Most late recurrence is considered to be MC, because MC depends not on the malignant potential of the resected HCC, but rather, on the degree of hepatitis or cirrhosis of the remnant liver (37)(38)(39)(40). In contrast, it seems that IM is likely responsible for the majority of early recurrence within the first two postoperative years, because IM denotes the existence of non-visible intrahepatic metastasis at primary surgery (39,40).…”

Section: Discussionmentioning

confidence: 99%

“…Most late recurrence is considered to be MC, because MC depends not on the malignant potential of the resected HCC, but rather, on the degree of hepatitis or cirrhosis of the remnant liver (37)(38)(39)(40). In contrast, it seems that IM is likely responsible for the majority of early recurrence within the first two postoperative years, because IM denotes the existence of non-visible intrahepatic metastasis at primary surgery (39,40). Although the REACH score was developed to predict 1-year recurrence after surgery to increase the power of sensitivity for early recurrence in the training set, we were able to show that the AUC values of the REACH score for both 1 and 2-year recurrence were higher than in any of the other systems used to analyze the validation set.…”

Section: Discussionmentioning

confidence: 99%

A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy

et al. 2018

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Abstract. We previously reported the effectiveness of the product of tumor number and size (NxS factor) for the prognosis of hepatocellular carcinoma (HCC) in patients following hepatectomy. The present study aimed to propose a new score based on the NxS factor to predict HCC recurrence following hepatectomy. A total of 406 patients who underwent hepatectomy for HCC at Osaka University Graduate School of Medicine were retrospectively analyzed to develop the new score. Among clinicopathological factors, including the NxS factor, the marker subset that achieved the best performance for prediction of early recurrence was assessed, and a prognostic model for HCC recurrence after curative hepatectomy (REACH) was developed. As the validation set, 425 patients who underwent hepatectomy for HCC at Yamaguchi University Graduate School of Medicine and Shimonoseki Medical Center were analyzed, and the prognostic ability of the REACH score was compared with that of well-known staging systems. Following analysis, the REACH score was constructed using six covariates (NxS factor, microscopic hepatic vein invasion, differentiation, serum albumin, platelet count and indocyanine green retention rate at 15 min). In the validation set, the REACH score predicted early recurrence in 73 of 81 samples, with a sensitivity of 89% and a specificity of 58%. The area under the curve (AUC) of the receiver operating characteristic curve of the REACH score was 0.78 and 0.74, respectively, for 1-and 2-year recurrence after hepatectomy; each AUC was higher than that of any of the other staging systems. Survival analysis indicated the REACH score had the best predictive value in disease-free and overall survival. The present findings demonstrated that the REACH score may be used to classify patients with HCC into high-and low-risk of recurrence, and to predict subsequent survival following hepatic resection.

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“…27,209,[213][214][215][216]219 This suggests that the majority of recurrences are due to dissemination from the primary tumor and not metachronous tumors developing in a liver with cirrhosis. 217,220 Furthermore, recurrence due to dissemination is more likely to appear during the first 3 years of follow-up. 218 There is no effective adjuvant therapy that can reduce recurrence rates.…”

Section: Risk Of Recurrencementioning

confidence: 99%

Management of Hepatocellular Carcinoma *

2005

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Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas

Cited by 108 publications

References 28 publications

Novel identification of zyxin upregulations in the motile phenotype of hepatocellular carcinoma

Novel identification of zyxin upregulations in the motile phenotype of hepatocellular carcinoma

A new prognostic model for hepatocellular carcinoma recurrence after curative hepatectomy

Management of Hepatocellular Carcinoma *

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