Therapy-induced expression of NF-kappa;B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation

J. G. Izzo, X. Wu, T. T. Wu, P. Huang, J. S. Lee, Z. Liao, J. H. Lee, M. S. Bhutani, W. Hofstetter, D. Maru, M. C. Hung, Jaffer A. Ajani

Research output: Contribution to journalArticle

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Abstract

Activated nuclear factor-kappa B (NF-κB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF-κB prior to any therapy portends poor prognosis, and it is also known that activated NF-κB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment-induced activation of NF-κB (meaning their cancers activate NF-κB during or after therapy) is not been reported. We hypothesized that the treatment-induced activation of NF-κB would impart poor prognosis similar to that imparted by constitutively activated NF-κB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre- and post-therapy cancer tissue available were selected. Pre- and post-therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF-κB. The overall survival (OS) and disease-free survival were assessed and compared for patients who had intrinsic constitutively activated NF-κB cancer with those who had induced activation of NF-κB only post-therapy. A total of 41 patients with LEA were investigated. Twenty-five patients had NF-κB positive cancer at baseline, and 16 had NF-κB negative cancer at baseline but became positive post-therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease-free survival (P = 0.86), and median survivals (Converters: 24 months [95% confidence intervals: 7.78 to 40.22] vs. Nonconverters: 34.13 months [95% confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF-κB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre-therapy evaluation of NF-κB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti-NF-κB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF-κB or cancer may have to be monitored during therapy with biomarker assessments.

Original languageEnglish (US)
Pages (from-to)127-132
Number of pages6
JournalDiseases of the Esophagus
Volume22
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

NF-kappa B
Esophageal Neoplasms
Neoplasms
Therapeutics
Adenocarcinoma
Survival
Cell- and Tissue-Based Therapy
Disease-Free Survival
Confidence Intervals

Keywords

  • Chemoradiation-resistance
  • Esophageal cancer
  • NF-κB

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Therapy-induced expression of NF-kappa;B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation. / Izzo, J. G.; Wu, X.; Wu, T. T.; Huang, P.; Lee, J. S.; Liao, Z.; Lee, J. H.; Bhutani, M. S.; Hofstetter, W.; Maru, D.; Hung, M. C.; Ajani, Jaffer A.

In: Diseases of the Esophagus, Vol. 22, No. 2, 2009, p. 127-132.

Research output: Contribution to journalArticle

Izzo, JG, Wu, X, Wu, TT, Huang, P, Lee, JS, Liao, Z, Lee, JH, Bhutani, MS, Hofstetter, W, Maru, D, Hung, MC & Ajani, JA 2009, 'Therapy-induced expression of NF-kappa;B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation', Diseases of the Esophagus, vol. 22, no. 2, pp. 127-132. https://doi.org/10.1111/j.1442-2050.2008.00884.x
Izzo, J. G. ; Wu, X. ; Wu, T. T. ; Huang, P. ; Lee, J. S. ; Liao, Z. ; Lee, J. H. ; Bhutani, M. S. ; Hofstetter, W. ; Maru, D. ; Hung, M. C. ; Ajani, Jaffer A. / Therapy-induced expression of NF-kappa;B portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation. In: Diseases of the Esophagus. 2009 ; Vol. 22, No. 2. pp. 127-132.
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abstract = "Activated nuclear factor-kappa B (NF-κB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF-κB prior to any therapy portends poor prognosis, and it is also known that activated NF-κB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment-induced activation of NF-κB (meaning their cancers activate NF-κB during or after therapy) is not been reported. We hypothesized that the treatment-induced activation of NF-κB would impart poor prognosis similar to that imparted by constitutively activated NF-κB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre- and post-therapy cancer tissue available were selected. Pre- and post-therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF-κB. The overall survival (OS) and disease-free survival were assessed and compared for patients who had intrinsic constitutively activated NF-κB cancer with those who had induced activation of NF-κB only post-therapy. A total of 41 patients with LEA were investigated. Twenty-five patients had NF-κB positive cancer at baseline, and 16 had NF-κB negative cancer at baseline but became positive post-therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease-free survival (P = 0.86), and median survivals (Converters: 24 months [95{\%} confidence intervals: 7.78 to 40.22] vs. Nonconverters: 34.13 months [95{\%} confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF-κB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre-therapy evaluation of NF-κB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti-NF-κB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF-κB or cancer may have to be monitored during therapy with biomarker assessments.",
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AU - Izzo, J. G.

AU - Wu, X.

AU - Wu, T. T.

AU - Huang, P.

AU - Lee, J. S.

AU - Liao, Z.

AU - Lee, J. H.

AU - Bhutani, M. S.

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AU - Maru, D.

AU - Hung, M. C.

AU - Ajani, Jaffer A.

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N2 - Activated nuclear factor-kappa B (NF-κB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF-κB prior to any therapy portends poor prognosis, and it is also known that activated NF-κB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment-induced activation of NF-κB (meaning their cancers activate NF-κB during or after therapy) is not been reported. We hypothesized that the treatment-induced activation of NF-κB would impart poor prognosis similar to that imparted by constitutively activated NF-κB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre- and post-therapy cancer tissue available were selected. Pre- and post-therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF-κB. The overall survival (OS) and disease-free survival were assessed and compared for patients who had intrinsic constitutively activated NF-κB cancer with those who had induced activation of NF-κB only post-therapy. A total of 41 patients with LEA were investigated. Twenty-five patients had NF-κB positive cancer at baseline, and 16 had NF-κB negative cancer at baseline but became positive post-therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease-free survival (P = 0.86), and median survivals (Converters: 24 months [95% confidence intervals: 7.78 to 40.22] vs. Nonconverters: 34.13 months [95% confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF-κB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre-therapy evaluation of NF-κB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti-NF-κB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF-κB or cancer may have to be monitored during therapy with biomarker assessments.

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