Microdissection–Based Allelotyping Discriminates De Novo Tumor From Intrahepatic Spread in Hepatocellular Carcinoma

Finkelstein, Sydney; Marsh, Wallis; Demetris, Anthony J.; Swalsky, Patricia A.; Sasatomi, Eizaburo; Bonham, Andrew; Subotin, Michael; Dvorchik, Igor

doi:10.1053/jhep.2003.50134

Cited by 102 publications

(80 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, patients with early recurrence mostly died of cancer and were usually predicted by adverse tumor features (7,8,15,32). However, in the present investigation, long-term survival was affected by tumoral and clinical characteristics in different ways.…”

Section: Discussionmentioning

confidence: 51%

“…However, the risk of tumor recurrence and associated prognosis changes over time. In the first 2 years, tumor recurrences most likely represent intrahepatic metastatic dissemination of the initial resected tumor (7)(8)(9) and consequently imply a worse prognosis. After 2 years, recurrences more often indicate de novo tumors, implying a better prognosis and more risk of dying due to worsening of the underlying liver function, which might have progressed in the meanwhile.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients

Cucchetti

Piscaglia²,

Cescon³

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Survival estimates are commonly reported as actuarial survival after the first observation, but future survival probabilities can change over time. Conditional survival is a measure of prognosis for patients who have sometimes already survived several years since diagnosis; however, data on conditional survival for cirrhotic patients, resected for hepatocellular carcinoma (HCC), are lacking.Experimental Design: Clinical data from 300 consecutive cirrhotic patients who underwent HCC resection were reviewed and the actuarial survival estimated. The 5-year conditional survival was calculated as CS ¼ S(x þ 5)/S(x) and represents the probability of surviving an additional 5 years, given that the patient has already survived x years.Results: The 3-, 5-, and 10-year survival rates were, respectively, 69.0%, 57.7%, and 25.3% and were lower in cases of portal hypertension, Model for End-stage Liver Disease (MELD) score !9, United Network for Organ-Sharing T3 tumor, GIII-GIV tumors, and microscopic vascular invasion. However, the 5-year conditional survival calculation showed that patients resected for more advanced (T3) tumors or with adverse histologic features will experience the same survival probabilities as patients with less advanced tumors or favorable histology from the third year after surgery onward, as they had probably escaped recurrence from intrahepatic metastases. Patients who underwent repeated hepatectomy for recurrence presented higher conditional survival.Conclusions: Conditional survival showed that the impact of different variables influencing survival is not linear over time after hepatic resection. Information derived from conditional survival can be used to better manage patients with HCCs, including the potential future setting of adjuvant therapies and the choice of listing, or not, for transplantation resected patients not recurring within 2 years.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients

Cucchetti

Piscaglia²,

Cescon³

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…15,16 Mutations which are present in a large proportion of cells more likely have been acquired earlier then mutations present in lesser numbers of cells with more localized distribution. 10,11,17 These molecular changes have not yet been previously described in cytology specimens where such information could greatly impact patient management. Our objective was to extend molecular studies to cytology specimens to determine the feasibility and effectiveness of mutation temporal profile determination in the anticipation that such information can potentially be used to render a more definitive cytologic diagnosis for pancreatic and biliary neoplasms.…”

mentioning

confidence: 99%

Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology

et al. 2006

View full text Add to dashboard Cite

Neoplastic progression is characterized by clonal expansion of tumor cells associated with accumulation of mutational damage. The timing of mutation acquisition could be of value in distinguishing preneoplastic conditions from early and advanced cancer as well as characterizing tumor aggressiveness and treatment response. Using quantitative methods applied to microdissected cell clusters selected according to cytomorphologic features, we sought to demonstrate the feasibility and efficacy for determining the time and course of mutation accumulation in pancreatobiliary cytology specimens. In all, 40 pancreatic duct and 21 biliary brushing cytology specimens were retrieved from the cytology database. Xylene-resistant markings were placed on the slide underside and coverslips removed. Clusters of benign, atypical and malignant cells were manually microdissected and DNA extracted. Mutations (allelic imbalance) (loss of heterozygosity) were quantitatively determined for a broad panel of 15 markers (1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q) as well as point mutation in K-ras-2 using PCR/capillary electrophoresis. Time course was based on earlier mutations having a higher proportion of mutant DNA for a particular marker. The descending frequency of detectable mutational involvement in pancreatic cytology was K-ras-2 point mutation (58%), 3p25-26 and 17q21 (35%), 5q23 (33%), 1p36 (28%), followed by the remaining molecular markers. The descending frequency of mutational content in bile duct cytology was 17p13, 1p36, 3p25-26, and 5q23 followed by remaining molecular markers. K-ras-2 point mutation was not seen in bile duct specimens. While there was overlap in the spectrum of mutational markers in pancreatic duct and biliary brushing cytology, the temporal profile was significantly different (Po0.001). Pancreatic and biliary neoplasia progression involves distinct subset of accumulated defined mutations. Determination of timing of the mutational damage in cytologic material could be incorporated in the work-up and help in making a more definitive diagnosis of malignancy in pancreatobiliary cytology specimens.

show abstract

“…Tumour recurrence complicates 70% of cases at five years, reflecting either intrahepatic metastases (true recurrences) or the development of de novo tumours (Llovet et al, 2005). Based on comparative genomic hybridisation, DNA fingerprinting using loss of heterozygosity assays, or DNA microarray studies, it is estimated that just over half of recurrences correspond to intrahepatic metastases undetected by the time of resection, whereas less than half are de novo HCCs (Chen et al, 2000;Finkelstein et al, 2003;Ng et al, 2003). OLT is indicated in individuals who fulfil the "Milan criteria": patients with a single H C C o f u p t o f i v e c e n t i m e t r e s i n s i z e o r up to three nodules not larger than three centimetres each.…”

Section: Hcc: a Clinically Important End-stage Complication Of Chronimentioning

confidence: 99%

Liver Progenitor Cells, Cancer Stem Cells and Hepatocellular Carcinoma

Tirnitz-Parker¹,

Yeoh²,

Olynyk³

2012

Liver Regeneration

View full text Add to dashboard Cite

Microdissection–Based Allelotyping Discriminates De Novo Tumor From Intrahepatic Spread in Hepatocellular Carcinoma

Abstract: A total of 103 cases of hepatocellular carcinoma (HCC) arising in native livers discovered at the time of transplantation underwent allelic loss analysis. HCC mutational allelotyping targeted 10 genomic loci (1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q)

Cited by 102 publications

References 23 publications

Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients

Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients

Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology

Liver Progenitor Cells, Cancer Stem Cells and Hepatocellular Carcinoma

Contact Info

Product

Resources

About