title: Epidemiological use of rectal proliferation measures.
abstract: Measures of rectal mucosal proliferation have been developed and used in research clinical settings, but their utility for larger-scale epidemiological studies remains uncertain. We assessed the suitability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA)-labeling indices (LIs) in the setting of a multicenter clinical trial of adenoma recurrence. Subjects at participating practices were asked to permit biopsy of normal rectal mucosa during a colonoscopy scheduled for other reasons. PCNA and BrdUrd labeling was performed, and corresponding LIs were computed. In general, subjects were willing to undergo biopsy during their scheduled procedures; less than 10% refused. Specimen preparation for PCNA was acceptable; the mean number of scorable crypts (+/- SE) was 12.99 +/- 0.37. Preparation for BrdUrd labeling was less successful, with a higher proportion of unscorable specimens and a lower mean number of scorable crypts. Among the 54 specimens with both LIs computed, the LI for PCNA was modestly higher than that for BrdUrd LI (4.1 +/- 0.2 and 3.7 +/- 0.2 respectively; P = 0.03). The rank order correlation between the two indices was 0.38). There was variation across centers in the PCNA LIs but few differences according to number of crypts scored. Measurement of rectal mucosal proliferation is feasible among endoscopy patients in large studies if PCNA is used; BrdUrd seems more difficult. The relationship between these two labels requires further study.
authors.affiliation: Dartmouth Medical School, Hanover, New Hampshire 03755.
authors.forename: J A
authors.initials: JA
authors.lastname: Baron
authors.forename: M J
authors.initials: MJ
authors.lastname: Wargovich
authors.forename: T D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: R
authors.initials: R
authors.lastname: Sandler
authors.forename: R
authors.initials: R
authors.lastname: Haile
authors.forename: R
authors.initials: R
authors.lastname: Summers
authors.forename: R
authors.initials: R
authors.lastname: van Stolk
authors.forename: R
authors.initials: R
authors.lastname: Rothstein
authors.forename: J
authors.initials: J
authors.lastname: Weiss
mesh_terms: D000236:Adenoma / Q000517:prevention & control; D001706:Biopsy; D001973:Bromodeoxyuridine / Q000032:analysis; D002119:Calcium Carbonate / Q000627:therapeutic use; D002455:Cell Division; D003113:Colonoscopy; D004311:Double-Blind Method; D004812:Epidemiologic Methods; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010919:Placebos; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012004:Rectal Neoplasms / Q000517:prevention & control; D012007:Rectum / Q000737:chemistry / Q000473:pathology*
chemical_list: D010919:Placebos; D018809:Proliferating Cell Nuclear Antigen; D001973:Bromodeoxyuridine; D002119:Calcium Carbonate