Premium
Nuclear morphometry as a biomarker for bronchial intraepithelial neoplasia: Correlation with genetic damage and cancer development
Author(s) -
Guillaud Martial,
le Riche Jean C.,
Dawe Chris,
Korbelik Jagoda,
Coldman Andy,
Wistuba Ignacio I.,
Park InWon,
Gazdar Adi,
Lam Stephen,
MacAulay Calum E.
Publication year - 2005
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.20101
Subject(s) - histopathology , biomarker , pathology , intraepithelial neoplasia , cancer , loss of heterozygosity , biology , surrogate endpoint , medicine , allele , prostate cancer , genetics , gene
Background Bronchial carcinomas are preceded by epithelial morphologic changes. The variation in interpretation of these grades of intraepithelial neoplasia makes it difficult to determine its natural history and utility of histopathology as a surrogate endpoint biomarker. The objective of this study was to quantitate morphologic changes of intraepitherlial neoplasia and validate its utility through correlation with histopathology, allelic loss, and cancer development. Methods Quantitative nuclear morphometry was performed on 47 normal bronchial biopsies and 28 invasive cancer to generate a morphometry index (MI) that was applied to 1,096 bronchial biopsies from 230 volunteers who were current smokers (≥25 pack‐years) and 30 patients who had cancer. In a subset of 631 biopsies, MI was correlated with frequency of loss of heterozygosity at nine chromosomal regions (14 polymorphic markers). Results A significant correlation was found between MI and allelic loss in six of nine chromosomal regions. As part of patient long‐term follow‐up, 12 sites that progressed to cancer were identified and had significantly increased MIs relative to nonprogressing sites. Significant overlap in the MIs was found between most grades of intraepithelial neoplasia. Conclusions In chemoprevention trials, nuclear morphometry can supplement histopathology as a Surrogate Endpont Biomarker (SEB) because it is quantitative, collelates well with genetic damage, and may predict cancer development. © 2004 Wiley‐Liss, Inc.