Karyometry in rectal mucosa of patients with previous colorectal adenomas.
OBJECTIVE
To determine whether karyometric measurements taken in biopsies from histologically normal-appearing rectal mucosa could serve as a biomarker for the risk of recurrence of polyps.


METHODS
Biopsies were taken from the rectal mucosa of cases with a prior history of colonic polyps at the baseline of the study. In 57 cases recurrent polyps occurred (R cases); in 72 cases no recurrent disease was found at the end of the study (NR cases). From each biopsy 100 nuclei were recorded at high resolution. After segmentation, feature extraction and selection of a discriminating subset of features, a number of discriminant functions were derived. Also, measures of nuclear abnormality were computed.


RESULTS
The differences in karyometricfeature values for nuclei from biopsies of cases with recurrent or nonrecurrent disease were very small and not notably expressed in the majority of nuclei. It was possible by focusing on nuclei showing clear deviations from normal to derive a discriminant function that exhibited a shift for the NR and R data sets. The distributions of discriminant function scores were then subjected to a second-order discriminant analysis to separate cases according to recurrence status. This function showed a statistically highly significant correlation with recurrence. At one extreme of its score distribution were 11 of 57 cases that had a recurrence, and at the other extreme were 8-10 of 72 cases that had no recurrence. The distributions of nuclear abnormality values for these subsets of cases were drastically different, with an average value of 1.72 for the group that may be at high risk for another recurrence and 1.02 for the group possibly at low risk. All cases with a prior history of colonic polyps showed a nuclear abnormality deviating from normal.


CONCLUSIONS
Measurement of a sample of 100 nuclei from the rectal mucosa will suggest, for approximately 10% of cases, that a high risk for recurrence of adenomatous polyps exists and, for a slightly lower proportion, confirm that the nuclei deviate only slightly from those from individuals with no history of colonic polyps. For the majority of cases with a prior history of adenoma, the nuclei in the biopsy show a notable deviation from normal, but the deviation is practically the same for cases that had a recurrence and those that did not. However, a tentative discriminant function (DF I,3) derived from the characteristics of the extreme cases correctly classified approximately 64% of nonrecurrent and 83% of recurrent cases using a Bayesian decision boundary.
Ranger-Moore
James
J
Department of Public Health and Optical Sciences Center, University of Arizona, Tucson, Arizona 85724, USA.
Frank
Denise
D
Lance
Peter
P
Alberts
David
D
Yozwiak
Michael
M
Bartels
Hubert G
HG
Einspahr
Janine
J
Bartels
Peter H
PH
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy / Q000473:pathology*; D000465:Algorithms; D001499:Bayes Theorem; D015415:Biomarkers; D001706:Biopsy; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016002:Discriminant Analysis; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D019044:Image Cytometry; D007090:Image Interpretation, Computer-Assisted; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D007620:Karyometry; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control; D011379:Prognosis; D012007:Rectum / Q000187:drug effects / Q000473:pathology*; D018709:Statistics, Nonparametric; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid