Allelic imbalance and microsatellite instability in resected Duke's D colorectal cancer

Ruby Kochhar, Kevin C. Halling, Shannon McDonnell, Daniel J Schaid, Amy J. French, Michael J. O'Connell, David M. Nagorney, Stephen N Thibodeau

Research output: Contribution to journalArticle

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Abstract

Hepatic resection is the treatment of choice for selected patients with liver metastases from colorectal cancer (CRC). Although the 5-year survival rate among patients after liver resection is 25-45%, 55-75% of patients die from progressive disease. The purpose of this study was to characterize molecular genetic alterations, including microsatellite instability and allelic imbalance, in patients with potentially curative resected liver metastases from CRC and to correlate these molecular features with clinical and pathologic characteristics. We examined DNA from formalin-fixed, paraffin-embedded archival tumor specimens from 141 surgically resected hepatic metastases from CRC. We used microsatellite markers localized to chromosome arms 5q, 8p, 10q, 15q, 17p, 18p, and 18q in a polymerase chain reaction based assay. Allelic imbalance at each locus and the presence of tumor microsatellite instability were correlated with clinicopathologic features of the tumor and clinical course of the patient. Microsatellite instability at multiple loci was seen in only 2.5% of resected liver metastases, a frequency significantly lower than that previously detected for primary CRC. Additionally, these findings had no significant correlation with disease-free survival or overall survival. Allelic imbalance at one or more loci was seen in 87%, of informative tumors. Allelic imbalance on chromosome 17p was seen in 84% of informative tumors, and its presence was associated with a significantly poor disease-free survival (p = 0.015) and overall survival (p = 0.05). These data suggest that allelic imbalance on chromosome 17p is an independent prognostic parameter in patients with potentially curative resected liver metastases from CRC. Such alterations could provide a useful stratification criterion for adjuvant therapy for patients who have undergone curative resection of liver metastases from CRC.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalDiagnostic Molecular Pathology
Volume6
Issue number2
DOIs
StatePublished - Apr 1997

Fingerprint

Allelic Imbalance
Microsatellite Instability
Colorectal Neoplasms
Liver
Neoplasm Metastasis
Chromosomes
Neoplasms
Disease-Free Survival
Survival
Paraffin
Microsatellite Repeats
Formaldehyde
Molecular Biology
Survival Rate
Polymerase Chain Reaction

Keywords

  • Allelic imbalance
  • Colorectal cancer
  • Hepatic resection
  • Microsatellite instability

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Allelic imbalance and microsatellite instability in resected Duke's D colorectal cancer. / Kochhar, Ruby; Halling, Kevin C.; McDonnell, Shannon; Schaid, Daniel J; French, Amy J.; O'Connell, Michael J.; Nagorney, David M.; Thibodeau, Stephen N.

In: Diagnostic Molecular Pathology, Vol. 6, No. 2, 04.1997, p. 78-84.

Research output: Contribution to journalArticle

Kochhar, Ruby ; Halling, Kevin C. ; McDonnell, Shannon ; Schaid, Daniel J ; French, Amy J. ; O'Connell, Michael J. ; Nagorney, David M. ; Thibodeau, Stephen N. / Allelic imbalance and microsatellite instability in resected Duke's D colorectal cancer. In: Diagnostic Molecular Pathology. 1997 ; Vol. 6, No. 2. pp. 78-84.
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abstract = "Hepatic resection is the treatment of choice for selected patients with liver metastases from colorectal cancer (CRC). Although the 5-year survival rate among patients after liver resection is 25-45{\%}, 55-75{\%} of patients die from progressive disease. The purpose of this study was to characterize molecular genetic alterations, including microsatellite instability and allelic imbalance, in patients with potentially curative resected liver metastases from CRC and to correlate these molecular features with clinical and pathologic characteristics. We examined DNA from formalin-fixed, paraffin-embedded archival tumor specimens from 141 surgically resected hepatic metastases from CRC. We used microsatellite markers localized to chromosome arms 5q, 8p, 10q, 15q, 17p, 18p, and 18q in a polymerase chain reaction based assay. Allelic imbalance at each locus and the presence of tumor microsatellite instability were correlated with clinicopathologic features of the tumor and clinical course of the patient. Microsatellite instability at multiple loci was seen in only 2.5{\%} of resected liver metastases, a frequency significantly lower than that previously detected for primary CRC. Additionally, these findings had no significant correlation with disease-free survival or overall survival. Allelic imbalance at one or more loci was seen in 87{\%}, of informative tumors. Allelic imbalance on chromosome 17p was seen in 84{\%} of informative tumors, and its presence was associated with a significantly poor disease-free survival (p = 0.015) and overall survival (p = 0.05). These data suggest that allelic imbalance on chromosome 17p is an independent prognostic parameter in patients with potentially curative resected liver metastases from CRC. Such alterations could provide a useful stratification criterion for adjuvant therapy for patients who have undergone curative resection of liver metastases from CRC.",
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