Classification and Risk Assessment of Individuals with Familial Polyposis, Gardner's Syndrome, and Familial Non-Polyposis Colon Cancer from [3H]Thymidine Labeling Patterns in Colonic Epithelial Cells

Martin Lipkin, William A. Blattner, Eldon J. Gardner, Randall W. Burt, Henry T. Lynch, Eleanor Deschner, Sidney Winawer, Joseph F. Fraumeni

Research output: Contribution to journalArticle

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Abstract

A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [3H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance.

Original languageEnglish
Pages (from-to)4201-4207
Number of pages7
JournalCancer Research
Volume44
Issue number9
StatePublished - Sep 1 1984
Externally publishedYes

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Gardner Syndrome
Adenomatous Polyposis Coli
Colonic Neoplasms
Thymidine
Epithelial Cells
Mucous Membrane
Population
Pedigree
Observation
Biopsy
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Classification and Risk Assessment of Individuals with Familial Polyposis, Gardner's Syndrome, and Familial Non-Polyposis Colon Cancer from [3H]Thymidine Labeling Patterns in Colonic Epithelial Cells. / Lipkin, Martin; Blattner, William A.; Gardner, Eldon J.; Burt, Randall W.; Lynch, Henry T.; Deschner, Eleanor; Winawer, Sidney; Fraumeni, Joseph F.

In: Cancer Research, Vol. 44, No. 9, 01.09.1984, p. 4201-4207.

Research output: Contribution to journalArticle

Lipkin, Martin ; Blattner, William A. ; Gardner, Eldon J. ; Burt, Randall W. ; Lynch, Henry T. ; Deschner, Eleanor ; Winawer, Sidney ; Fraumeni, Joseph F. / Classification and Risk Assessment of Individuals with Familial Polyposis, Gardner's Syndrome, and Familial Non-Polyposis Colon Cancer from [3H]Thymidine Labeling Patterns in Colonic Epithelial Cells. In: Cancer Research. 1984 ; Vol. 44, No. 9. pp. 4201-4207.
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abstract = "A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [3H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92{\%}. Further application of the method to asymptomatic family members believed to be at 50{\%} risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance.",
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