An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial

Can we detect informative differences among individuals' proliferation measures amid the noise?

Lisa M. McShane, Martin Kulldorff, Michael J Wargovich, Cindy Woods, Madhu Purewal, Laurence S. Freedman, Donald K. Corle, Randall W. Burt, Donna J. Mateski, Michael Lawson, Elaine Lanza, Barbara O'Brien, William Lake, James Moler, Arthur Schatzkin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U.S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within- participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume7
Issue number7
StatePublished - Jul 1998
Externally publishedYes

Fingerprint

Polyps
Individuality
Noise
Biopsy
Proliferating Cell Nuclear Antigen
Bromodeoxyuridine
Reading
Colorectal Neoplasms
National Cancer Institute (U.S.)

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial : Can we detect informative differences among individuals' proliferation measures amid the noise? / McShane, Lisa M.; Kulldorff, Martin; Wargovich, Michael J; Woods, Cindy; Purewal, Madhu; Freedman, Laurence S.; Corle, Donald K.; Burt, Randall W.; Mateski, Donna J.; Lawson, Michael; Lanza, Elaine; O'Brien, Barbara; Lake, William; Moler, James; Schatzkin, Arthur.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 7, No. 7, 07.1998, p. 605-612.

Research output: Contribution to journalArticle

McShane, LM, Kulldorff, M, Wargovich, MJ, Woods, C, Purewal, M, Freedman, LS, Corle, DK, Burt, RW, Mateski, DJ, Lawson, M, Lanza, E, O'Brien, B, Lake, W, Moler, J & Schatzkin, A 1998, 'An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: Can we detect informative differences among individuals' proliferation measures amid the noise?', Cancer Epidemiology Biomarkers and Prevention, vol. 7, no. 7, pp. 605-612.
McShane, Lisa M. ; Kulldorff, Martin ; Wargovich, Michael J ; Woods, Cindy ; Purewal, Madhu ; Freedman, Laurence S. ; Corle, Donald K. ; Burt, Randall W. ; Mateski, Donna J. ; Lawson, Michael ; Lanza, Elaine ; O'Brien, Barbara ; Lake, William ; Moler, James ; Schatzkin, Arthur. / An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial : Can we detect informative differences among individuals' proliferation measures amid the noise?. In: Cancer Epidemiology Biomarkers and Prevention. 1998 ; Vol. 7, No. 7. pp. 605-612.
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abstract = "We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U.S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within- participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.",
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