Review for 10.1186/1471-230X-8-1 (2008)

Reviewer's report
Title:Multilayered epithelium in a rat model and human Barrett's esophagus:
Expression patterns of transcription factors and differentiation markers
Version: 1Date:26 September 2007
Reviewer: kausilia K krishnadath
Reviewer's report:
This report by Xiaoxin Chen et al: Multilayered epithelium in a rat model and
human Barrett's esophagus: Expression patterns of transcription factors and
differentiation markers, attempts to find more evidence that multilayered
epithelium is a precursor lesion of Barrett's esophagus by studying its
appearance in a surgical rat Barrett esophagus model. The finding confirms the
existence of this type of epithelium in the Barrett model but still does not provide
evidence that this is truly a precursor lesion of Barrett, but rather an incomplete
differentiation showing features of both squamous and columnar epithelium.
The paper in general is well written and easy to follow. There is however some
major comments that need to be addressed.
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Major Compulsory Revisions (that the author must respond to before a decision
on publication can be reached)
1. The finding confirms the existence of MLE in the Barrett model but still does
not provide evidence that this is truly a precursor lesion of Barrett (thus precedes
development of BE), but it seems to be rather an incomplete differentiation
showing features of both squamous and columnar epithelium. Therefore, it is not
justified to refer to these lesions as 'precursor' lesions. It would make more sense
to refer to these lesions as an incomplete or multi-directional differentiation type
or junctional type of epithelium. Also most of these lesions are found at the
transition zone between squamous and the IM. How do the authors know that
this is not simply an artifact that is a result of tangentional cutting of the tissues??
2. Since the authors presume that the MLE is the precursor for BE, it would have
sense to sacrifice the model animals at different time points for sequential
studying development of these lesions and proof that these lesions develop prior
to the development of intestinal metaplasia resembling Barrett's. The question is
whether the authors looked into this matter and why this set up was not followed.
3. The authors do not see any CDX-2 in the rat MLE, but do see Villin expression
in up to 27%. Since CDX-2 is the transcriptional regulator of Villin expression,
this discrepancy should be discussed.
4. From these results the authors conclude that the finding of MLE strongly
support the existence of pluripotent stem cells in the esophagus. Again there is
no causal or direct evidence in this study that MLE precedes IM development,
therefore this remark (last sentence of discussion) should be softened.
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Minor Essential Revisions (such as missing labels on figures, or the wrong use of
a term, which the author can be trusted to correct)
1. The discussion section is somewhat long. The description of the different
factors can be shortened and there should be more discussion on the results
(see above)
2. In the result section it is misleading tot state that all human samples contained
MLE, since these samples were selected for MEL. Better is that by selection all
human samples contained MLE.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'