Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

Matias E. Valsecchi, Thomas Holdbrook, Benjamin E. Leiby, Edward Pequignot, Susan J. Littman, Charles J. Yeo, Jonathan R. Brody, Agnieszka K. Witkiewicz

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Abstract

Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).Results: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively). Similar results were obtained for DFS.Conclusions: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.

Original languageEnglish (US)
Article number104
JournalBMC Cancer
Volume12
DOIs
StatePublished - Mar 22 2012

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Pancreatic Ductal Carcinoma
Disease-Free Survival
Adenocarcinoma
Immunohistochemistry
gemcitabine
Pancreatic Neoplasms
Polymerase Chain Reaction
Survival
Drug Therapy
Survival Analysis
Tumor Biomarkers
Paraffin
Formaldehyde
Lung Neoplasms
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma? / Valsecchi, Matias E.; Holdbrook, Thomas; Leiby, Benjamin E.; Pequignot, Edward; Littman, Susan J.; Yeo, Charles J.; Brody, Jonathan R.; Witkiewicz, Agnieszka K.

In: BMC Cancer, Vol. 12, 104, 22.03.2012.

Research output: Contribution to journalArticle

Valsecchi, Matias E. ; Holdbrook, Thomas ; Leiby, Benjamin E. ; Pequignot, Edward ; Littman, Susan J. ; Yeo, Charles J. ; Brody, Jonathan R. ; Witkiewicz, Agnieszka K. / Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?. In: BMC Cancer. 2012 ; Vol. 12.
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abstract = "Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).Results: A total of 94 patients with resected PDA were included in this study. Most of them (87{\%}) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68{\%} had enough information to estimate DFS. IHC analysis revealed information for 99{\%} (93/94) and 100{\%} of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52{\%}) and 79 (84{\%}) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively). Similar results were obtained for DFS.Conclusions: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.",
author = "Valsecchi, {Matias E.} and Thomas Holdbrook and Leiby, {Benjamin E.} and Edward Pequignot and Littman, {Susan J.} and Yeo, {Charles J.} and Brody, {Jonathan R.} and Witkiewicz, {Agnieszka K.}",
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T1 - Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

AU - Valsecchi, Matias E.

AU - Holdbrook, Thomas

AU - Leiby, Benjamin E.

AU - Pequignot, Edward

AU - Littman, Susan J.

AU - Yeo, Charles J.

AU - Brody, Jonathan R.

AU - Witkiewicz, Agnieszka K.

PY - 2012/3/22

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N2 - Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).Results: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively). Similar results were obtained for DFS.Conclusions: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.

AB - Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).Results: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively). Similar results were obtained for DFS.Conclusions: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.

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