Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas

Yamada, Satoshi; Ohira, Miki; Hara, Hiroshi; Ando, Kiyohiro; Takayasu, Hajime; Suzuki, Yutaka; Sugano, Sumio; Hirata, Takahiro; Goto, Takeshi; Matsunaga, Tadashi; Hiyama, Eiso; Hayashi, Yutaka; Ando, Hisami; Suita, Sachiyo; Kaneko, Michio; Sasaki, Fumio; Hashizume, Kohei; Ohnuma, Naomi; Nakagawara, Akira

doi:10.1038/sj.onc.1207782

Cited by 112 publications

(90 citation statements)

References 68 publications

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“…Plk1 is overexpressed in a range of human tumors, including prostate tumors, ovarian carcinomas, hepatoblastomas and melanomas, and Plk1 overexpression was shown to coincide with bad prognosis (Kneisel et al, 2002;Weichert et al, 2004a, b;Yamada et al, 2004). Therefore, Plk1 is useful as a prognostic marker for outcome of disease.…”

Section: Plk1 and Cancermentioning

confidence: 99%

Getting in and out of mitosis with Polo-like kinase-1

2005

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Section: Plk1 and Cancermentioning

confidence: 99%

Getting in and out of mitosis with Polo-like kinase-1

2005

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“…[61][62][63] Other pathways implicated in hepatoblastoma include Sonic Hedgehog, Notch, Hepatocyte Growth Factor/c-Met (PI3K/AKT and MAPK signaling activation), the Insulin-Like Growth Factor (IGF) pathway, and others [64][65][66][67][68][69] (Table 4). Molecular profiling of hepatoblastoma [70][71][72][73][74] has identified groups of tumors and gene signatures that appear useful to further stratify these patients. 71,75 Further characterization of these biological mechanisms and the integration of molecular and clinical parameters into current morphologic classifications will be necessary to accurately diagnose and stratify pediatric liver tumor patients, similarly to other pediatric malignancies.…”

Section: Immunohistochemistry and Other Ancillary Studiesmentioning

confidence: 99%

Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium

Alaggio²,

et al. 2014

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Liver tumors are rare in children, and their diagnoses may be challenging particularly because of the lack of a current consensus classification system. Systematic central histopathological review of these tumors performed as part of the pediatric collaborative therapeutic protocols has allowed the identification of histologic subtypes with distinct clinical associations. As a result, histopathology has been incorporated within the Children's Oncology Group (COG) protocols, and only in the United States, as a risk-stratification parameter and for patient management. Therefore, the COG Liver Tumor Committee sponsored an International Pathology Symposium in March 2011 to discuss the histopathology and classification of pediatric liver tumors, and hepatoblastoma in particular, and work towards an International Pediatric Liver Tumors Consensus Classification that would be required for international collaborative projects. Twenty-two pathologists and experts in pediatric liver tumors, including those serving as central reviewers for the COG, European Socié té Internationale d'Oncologie Pé diatrique, Gesellschaft fü r Pä diatrische Onkologie und Hä matologie, and Japanese Study Group for Pediatric Liver Tumors protocols, as well as pediatric oncologists and surgeons specialized in this field, reviewed more than 50 pediatric liver tumor cases and discussed classic and newly reported entities, as well as criteria for their classification. This symposium represented the first collaborative step to develop a classification that may lead to a common treatment-stratification system incorporating tumor histopathology. A standardized, clinically meaningful classification will also be necessary to allow the integration of new biological parameters and to move towards clinical algorithms based on patient characteristics and tumor genetics, which should improve future patient management and outcome.

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“…The present clinical factors predicting outcome include the level of alpha-feto protein, histology, disease stage and growth pattern of the tumor. [2][3][4] Chromosomal gains of 2q, 8q and 20 and high expression of telomerase or PLK1 were shown to be moleculargenetic markers predicting poor outcome [5][6][7][8] ; however, none have been proven to be independent prognostic factors by multivariate analysis.…”

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The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients

Honda

Haruta

Sugawara

et al. 2008

Intl Journal of Cancer

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Despite the progress of therapy, outcomes of advanced hepatoblastoma patients who are refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the mortality rate, novel prognostic markers are needed for better therapy planning. We examined the methylation status of 13 candidate tumor suppressor genes in 20 hepatoblastoma tumors by conventional methylation-specific PCR (MSP) and found hypermethylation in 3 of the 13 genes. We analyzed the methylation status of these 3 genes (RASSF1A, SOCS1 and CASP8) in 97 tumors and found hypermethylation in 30.9, 33.0 and 15.5%, respectively. Univariate analysis showed that only the methylation status of RASSF1A but not the other 2 genes predicted the outcome, and multivariate analysis showed a weak contribution of RASSF1A methylation to overall survival. Using quantitative MSP, we found RASSF1A methylation in 44.3% of the 97 tumors. CTNNB1 mutation was detected in 67.0% of the 97 tumors. While univariate analysis demonstrated RASSF1A methylation, CTNNB1 mutation and other clinicopathological variables as prognostic factors, multivariate analysis identified RASSF1A methylation (p 5 0.043; relative risk 9.39) and the disease stage (p 5 0.002; relative risk 7.67) but not CTNNB1 mutation as independent prognostic factors. In survival analysis of 33 patients in stage 3B or 4, patients with unmethylated tumor had better overall survival than those with methylated tumor (p 5 0.035). RASSF1A methylation may be a promising moleculargenetic marker to predict the treatment outcome and may be used to stratify patients when clinical trials are carried out. ' 2008 Wiley-Liss, Inc.Key words: RASSF1A; CTNNB1; quantitative MSP; hepatoblastoma; prognostic factor Hepatoblastoma is a rare malignant neoplasm of the liver, with an incidence of 0.5-1.5 per million children. 1 Remarkable progress in clinical outcome has been achieved in the past 20 years due to advances in chemotherapy and surgical procedures; however, the mortality rate remains 20-30% and treatment results in patients in advanced stages who are refractory to standard preoperative chemotherapy regimens are unsatisfactory. 2,3 To improve the mortality of these patients, innovative treatment and potent prognostic markers for better therapy planning are needed. The present clinical factors predicting outcome include the level of alpha-feto protein, histology, disease stage and growth pattern of the tumor. 2-4 Chromosomal gains of 2q, 8q and 20 and high expression of telomerase or PLK1 were shown to be moleculargenetic markers predicting poor outcome 5-8 ; however, none have been proven to be independent prognostic factors by multivariate analysis.We previously reported that RASSF1A (RAS association domain family protein 1) methylation, found in 39% of 39 hepatoblastoma tumors, was correlated with poor outcome by univariate analysis. 9 Nevertheless, the article had some limitations that the number of tumors was not enough, the method used to detect the hypermethylation was suboptimal, and the prognostic signifi...

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Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas

Cited by 112 publications

References 68 publications

Getting in and out of mitosis with Polo-like kinase-1

Getting in and out of mitosis with Polo-like kinase-1

Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium

The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients

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