Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial

Nancy L. Cho, Mark Redston, Ann G. Zauber, Adelaide M. Carothers, Jason Hornick, Andrew Wilton, Stephen Sontag, Norman Nishioka, Francis M. Giardiello, John R. Saltzman, Chris Gostout, Craig J. Eagle, Ernest T. Hawk, Monica M. Bertagnolli

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P<0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of β-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor α, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalCancer Prevention Research
Volume1
Issue number1
DOIs
StatePublished - Jun 2008

Fingerprint

Celecoxib
Aberrant Crypt Foci
Adenoma
Biomarkers
Placebos
Catenins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Cho, N. L., Redston, M., Zauber, A. G., Carothers, A. M., Hornick, J., Wilton, A., ... Bertagnolli, M. M. (2008). Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial. Cancer Prevention Research, 1(1), 21-31. https://doi.org/10.1158/1940-6207.CAPR-07-0011

Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial. / Cho, Nancy L.; Redston, Mark; Zauber, Ann G.; Carothers, Adelaide M.; Hornick, Jason; Wilton, Andrew; Sontag, Stephen; Nishioka, Norman; Giardiello, Francis M.; Saltzman, John R.; Gostout, Chris; Eagle, Craig J.; Hawk, Ernest T.; Bertagnolli, Monica M.

In: Cancer Prevention Research, Vol. 1, No. 1, 06.2008, p. 21-31.

Research output: Contribution to journalArticle

Cho, NL, Redston, M, Zauber, AG, Carothers, AM, Hornick, J, Wilton, A, Sontag, S, Nishioka, N, Giardiello, FM, Saltzman, JR, Gostout, C, Eagle, CJ, Hawk, ET & Bertagnolli, MM 2008, 'Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial', Cancer Prevention Research, vol. 1, no. 1, pp. 21-31. https://doi.org/10.1158/1940-6207.CAPR-07-0011
Cho NL, Redston M, Zauber AG, Carothers AM, Hornick J, Wilton A et al. Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial. Cancer Prevention Research. 2008 Jun;1(1):21-31. https://doi.org/10.1158/1940-6207.CAPR-07-0011
Cho, Nancy L. ; Redston, Mark ; Zauber, Ann G. ; Carothers, Adelaide M. ; Hornick, Jason ; Wilton, Andrew ; Sontag, Stephen ; Nishioka, Norman ; Giardiello, Francis M. ; Saltzman, John R. ; Gostout, Chris ; Eagle, Craig J. ; Hawk, Ernest T. ; Bertagnolli, Monica M. / Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial. In: Cancer Prevention Research. 2008 ; Vol. 1, No. 1. pp. 21-31.
@article{d0c6119b614d46c4a8632496723240d7,
title = "Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial",
abstract = "Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P<0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of β-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor α, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial.",
author = "Cho, {Nancy L.} and Mark Redston and Zauber, {Ann G.} and Carothers, {Adelaide M.} and Jason Hornick and Andrew Wilton and Stephen Sontag and Norman Nishioka and Giardiello, {Francis M.} and Saltzman, {John R.} and Chris Gostout and Eagle, {Craig J.} and Hawk, {Ernest T.} and Bertagnolli, {Monica M.}",
year = "2008",
month = "6",
doi = "10.1158/1940-6207.CAPR-07-0011",
language = "English (US)",
volume = "1",
pages = "21--31",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - Aberrant crypt foci in the Adenoma Prevention with Celecoxib trial

AU - Cho, Nancy L.

AU - Redston, Mark

AU - Zauber, Ann G.

AU - Carothers, Adelaide M.

AU - Hornick, Jason

AU - Wilton, Andrew

AU - Sontag, Stephen

AU - Nishioka, Norman

AU - Giardiello, Francis M.

AU - Saltzman, John R.

AU - Gostout, Chris

AU - Eagle, Craig J.

AU - Hawk, Ernest T.

AU - Bertagnolli, Monica M.

PY - 2008/6

Y1 - 2008/6

N2 - Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P<0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of β-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor α, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial.

AB - Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P<0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of β-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor α, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial.

UR - http://www.scopus.com/inward/record.url?scp=57249089705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57249089705&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-07-0011

DO - 10.1158/1940-6207.CAPR-07-0011

M3 - Article

C2 - 19138933

AN - SCOPUS:57249089705

VL - 1

SP - 21

EP - 31

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 1

ER -