NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer

Soham D Puvvada, William K. Funkhouser, Kevin Greene, Allison Deal, Haitao Chu, Albert S. Baldwin, Joel E. Tepper, Bert H. O'Neil

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Purpose: NF-κB is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-κB that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-κB and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). Methods: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-κB was defined by nuclear expression of select components of NF-κB (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. Results: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91% for Bcl-3, 66% for p65, and 52% for p50 (all p < 0.05). Conclusions: Activation of canonical NF-κB subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-κB as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC.

Original languageEnglish (US)
Pages (from-to)181-188
Number of pages8
JournalOncology
Volume78
Issue number3-4
DOIs
StatePublished - Jun 2010
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Mucous Membrane
Neoplasm Metastasis
Neoplasms
Liver
Lymph Nodes
Survival
Proportional Hazards Models
Carcinogenesis
Transcription Factors
Retrospective Studies

Keywords

  • Colorectal carcinoma
  • NF-κB
  • P50
  • P65

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Puvvada, S. D., Funkhouser, W. K., Greene, K., Deal, A., Chu, H., Baldwin, A. S., ... O'Neil, B. H. (2010). NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer. Oncology, 78(3-4), 181-188. https://doi.org/10.1159/000313697

NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer. / Puvvada, Soham D; Funkhouser, William K.; Greene, Kevin; Deal, Allison; Chu, Haitao; Baldwin, Albert S.; Tepper, Joel E.; O'Neil, Bert H.

In: Oncology, Vol. 78, No. 3-4, 06.2010, p. 181-188.

Research output: Contribution to journalArticle

Puvvada, SD, Funkhouser, WK, Greene, K, Deal, A, Chu, H, Baldwin, AS, Tepper, JE & O'Neil, BH 2010, 'NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer', Oncology, vol. 78, no. 3-4, pp. 181-188. https://doi.org/10.1159/000313697
Puvvada SD, Funkhouser WK, Greene K, Deal A, Chu H, Baldwin AS et al. NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer. Oncology. 2010 Jun;78(3-4):181-188. https://doi.org/10.1159/000313697
Puvvada, Soham D ; Funkhouser, William K. ; Greene, Kevin ; Deal, Allison ; Chu, Haitao ; Baldwin, Albert S. ; Tepper, Joel E. ; O'Neil, Bert H. / NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer. In: Oncology. 2010 ; Vol. 78, No. 3-4. pp. 181-188.
@article{b7b285cad6f2423d8eedb2ec40ac5fb1,
title = "NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer",
abstract = "Purpose: NF-κB is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-κB that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-κB and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). Methods: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-κB was defined by nuclear expression of select components of NF-κB (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. Results: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91{\%} for Bcl-3, 66{\%} for p65, and 52{\%} for p50 (all p < 0.05). Conclusions: Activation of canonical NF-κB subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-κB as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC.",
keywords = "Colorectal carcinoma, NF-κB, P50, P65",
author = "Puvvada, {Soham D} and Funkhouser, {William K.} and Kevin Greene and Allison Deal and Haitao Chu and Baldwin, {Albert S.} and Tepper, {Joel E.} and O'Neil, {Bert H.}",
year = "2010",
month = "6",
doi = "10.1159/000313697",
language = "English (US)",
volume = "78",
pages = "181--188",
journal = "Oncology",
issn = "0030-2414",
publisher = "S. Karger AG",
number = "3-4",

}

TY - JOUR

T1 - NF-κB and Bcl-3 activation are prognostic in metastatic colorectal cancer

AU - Puvvada, Soham D

AU - Funkhouser, William K.

AU - Greene, Kevin

AU - Deal, Allison

AU - Chu, Haitao

AU - Baldwin, Albert S.

AU - Tepper, Joel E.

AU - O'Neil, Bert H.

PY - 2010/6

Y1 - 2010/6

N2 - Purpose: NF-κB is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-κB that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-κB and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). Methods: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-κB was defined by nuclear expression of select components of NF-κB (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. Results: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91% for Bcl-3, 66% for p65, and 52% for p50 (all p < 0.05). Conclusions: Activation of canonical NF-κB subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-κB as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC.

AB - Purpose: NF-κB is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-κB that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-κB and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). Methods: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-κB was defined by nuclear expression of select components of NF-κB (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. Results: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91% for Bcl-3, 66% for p65, and 52% for p50 (all p < 0.05). Conclusions: Activation of canonical NF-κB subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-κB as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC.

KW - Colorectal carcinoma

KW - NF-κB

KW - P50

KW - P65

UR - http://www.scopus.com/inward/record.url?scp=77951035570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951035570&partnerID=8YFLogxK

U2 - 10.1159/000313697

DO - 10.1159/000313697

M3 - Article

C2 - 20414006

AN - SCOPUS:77951035570

VL - 78

SP - 181

EP - 188

JO - Oncology

JF - Oncology

SN - 0030-2414

IS - 3-4

ER -