Review for 10.1186/1471-230X-8-56 (2008)

Reviewer's report
Title:Loss of PTEN expression is associated with colorectal cancer liver
metastasis and poor patient survival
Version: 1Date:2 June 2008
Reviewer: Milo Frattini
Reviewer's report:
In the manuscript “Loss of PTEN expression is associated with colorectal cancer
liver metastasis and poor patient survival” by Sawai et al, the Authors analyzed
69 primary colorectal cancers and related liver metastasis, and 70 primary
colorectal cancers without distant metastases, for the expression of PTEN
protein through immunohistochemistry. The Authors found a normal expression
in 62.9% of patients without liver metastases, and 24.6% of patients with liver
metastasis. Furthermore, the Authors reported that the 5-year survival rate was
higher in patients with PTEN normal expression with respect to those with PTEN
loss, in patients with liver metastasis (P=0.012). Therefore, the Authors
concluded that PTEN expression may be a prognostic marker for colorectal
cancer patients.
The work is well conceived and generally well written, with discussion and
colcusions supported by the data. However, some major and minor clarifications
are strictly required.
Major Compulsory Revisions
- The type of fixative used, the time of fixation and the time between tissue cut
and immunohistochemistry may have an influence on immunohistochemical
results: the Authors must describe this in details.
- What is the dilution of PTEN primary antibody? What is the type and the clone
of the primary antibody?
- The role of PTEN in colorectal cancer has acquired high relevance due to a
recent work, where it has been matched the level of PTEN protein expression
through immunohistochemistry and the clinical response to anti-EGFR targeted
therapies. In that paper (Frattini et al, BJC 2007), by applying a type of primary
antibody, immunohistochemical conditions and evaluation criteria already used
(for example, in breast cancer – Saal et al, Cancer Res 2005), it has been shown
that the loss of PTEN expression is observed in 40% of primary colorectal cancer
patients with synchronous or metachronous metastatic lesion (Frattini et all did
not report what type of metastatic lesion occurred, but we can assume that 80%
of cases showed a distant lesion located in the liver, according to the frequency
of liver metastasis occurrence in colorectal cancer patients). Therefore, the data
of the reported paper are not consistent with those of Saway and colleagues,
who, however, used a different type of primary antibody and different evaluation
criteria. The Authors must use the same evaluation criteria of the paper reporting
the relationship between PTEN expression and anti-EGFR therapies, and then
they have to verify the new percentages of PTEN loss. In case of discrepancies
with published data, the Authors must re-analyze their cohort of patients with the
published anti-PTEN primary antibody. If confirmed, the Authors should explain,
or at least hypothesize, the reason of this discrepancy.
Minor Essential Revisions
- In patients with liver metastasis, is the metastatic lesion synchronous or
metachronous?
- The Authors must discuss their data according to the published reports on
PTEN expression in colorectal cancers, especially to the previously cited paper.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.