Download Gene expression Profiling of Duodenal Biopsies

Gene Expression Profiling vs. histopathologic assessment
comparative analysis using a simplified classification scheme
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Hanna Bragde, Ulf Jansson, Ingvar Jarlsfelt, Jan Söderman
Division of Medical Diagnostics [H.B., I.J., J.S.], Department of Pediatrics [U.J.],
Ryhov County Hospital, Jönköping, SE-551 85, Sweden.
Objectives: Celiac disease (CD) is identified by histopathologic changes in the small
intestine which normalise during a gluten-free diet. The histopathologic assessment
(HA) is usually routine, but can be problematic. We have recently described
discriminant analysis (DA) of gene expression in duodenal biopsies, for diagnosis
and monitoring of CD (accepted for publication). Here we extend the results by
building the algorithms using a larger cohort of patients, and examine their
performance in relation to routine, clinical HA.
Methods: DA was based on gene expression of eight genes selected to reflect crypt
hyperplasia (MAD2L1, MKI67), villous atrophy (APOC3, CYP3A4), inflammatory
response (CXCL11, IL17A, CTLA4), and intestinal permeability (OCLN). The
classification algorithms were derived by fitting gene expression values to a simplified
histopathologic classification (Corazza et al. (2005, 2007)) of biopsies (assessed by a
single pathologist) from 53 paediatric cases. Performance of DA was investigated in
relation to a set of cases assessed during routine, clinical practice.
Results: DA correctly classified all cases (except grade A) present in the model using
leave-one-out cross-validation. There were too few grade A cases for crossvalidation, but the model resulted in distinct posterior probabilities for these biopsies.
Among 10 cases with primary, diagnostic biopsies there were four cases with a
normal mucosa and six cases with a lesioned mucosa according to routine, clinical
HA. For one of the cases with a histologically lesioned mucosa, DA disagrees.
However, for this case, DA presented a rather high posterior probability for grade B1
and reduced expression of villi genes was observed. Among five cases with
histologically normalised mucosa, assessed after gluten-free diet, one was classified
as grade A according to DA.
Conclusion: Using more cases per grade, it seems possible to establish DA as a
useful tool for assessing biopsies from patients investigated for CD.