Reviewer ’s report  
 
Title: Asso ciation between HER2 status in gastric cancer and clinicopathological features: a  
retrospective study using whole -tissue sections  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Lorenzo Nicol e 
 
Reviewer's report:  
 
Gastric Cancer (GC), remain a major health problem in developing countries where principal risk 
factors are largely diffuse. Advanced s tage management are limited to palliative supporting care, 
however larger worldwide metanalysis showed that about 18% of patients present a gastric 
cancer expressing Her -2 receptors that are a predictive factor of response to tyrosine kinase 
inhibitors suc h as trastuzumab. Use of trastuzumab in combination with chemotherapy has 
proved effective in improving survival in non -operable patients expressing Her -2. However, to 
date, prevalence of Her -2 expressing GC and related clinicopathological features in Braz ilian 
patients is still unknown, and the use of tyrosine kinase inhibitors is not yet adopted. The authors 
of this studies analyzed retrospectively with an immunohistochemical approach the prevalence of 
Her-2 expressing GCs, as well as correlation between Her-2 expression status and main 
clinicopathologial characteristics of GC. They have demonstrated in according with international 
data a relevant percentage of Her -2 positive GCs and thus, suggesting the appropriateness of the 
introduction of tyrosine kina se inhibitors in treatment of Her -2 positive patients with 
advanced/metastatic stage GC. The study is well conduct, however, I have some minor concerns 
that the authors should address:  
 
* I suggest adding a table summarizing data obtained from international  metanalysis that 
reported prevalence about Her -2 status in GCs and its correlation (where possible) with main 
clinicopathological features.  
 
* The paper could be improved by the addition of images of all techniques adopted for this 
study (SISH).  
 
 
 
 
 
 
 
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer re view policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Asso ciation between HER2 status in gastric cancer and clinicopathological features: a  
retrospective study using whole -tissue sections  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Lorenzo Nicol e 
 
Reviewer's report:  
 
Gastric Cancer (GC), remain a major health problem in developing countries where principal risk 
factors are largely diffuse. Advanced s tage management are limited to palliative supporting care, 
however larger worldwide metanalysis showed that about 18% of patients present a gastric 
cancer expressing Her -2 receptors that are a predictive factor of response to tyrosine kinase 
inhibitors suc h as trastuzumab. Use of trastuzumab in combination with chemotherapy has 
proved effective in improving survival in non -operable patients expressing Her -2. However, to 
date, prevalence of Her -2 expressing GC and related clinicopathological features in Braz ilian 
patients is still unknown, and the use of tyrosine kinase inhibitors is not yet adopted. The authors 
of this studies analyzed retrospectively with an immunohistochemical approach the prevalence of 
Her-2 expressing GCs, as well as correlation between Her-2 expression status and main 
clinicopathologial characteristics of GC. They have demonstrated in according with international 
data a relevant percentage of Her -2 positive GCs and thus, suggesting the appropriateness of the 
introduction of tyrosine kina se inhibitors in treatment of Her -2 positive patients with 
advanced/metastatic stage GC. The study is well conduct, however, I have some minor concerns 
that the authors should address:  
 
* I suggest adding a table summarizing data obtained from international  metanalysis that 
reported prevalence about Her -2 status in GCs and its correlation (where possible) with main 
clinicopathological features.  
 
* The paper could be improved by the addition of images of all techniques adopted for this 
study (SISH).  
 
 
 
 
 
 
 
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer re view policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Asso ciation between HER2 status in gastric cancer and clinicopathological features: a  
retrospective study using whole -tissue sections  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Lorenzo Nicol e 
 
Reviewer's report:  
 
Gastric Cancer (GC), remain a major health problem in developing countries where principal risk 
factors are largely diffuse. Advanced s tage management are limited to palliative supporting care, 
however larger worldwide metanalysis showed that about 18% of patients present a gastric 
cancer expressing Her -2 receptors that are a predictive factor of response to tyrosine kinase 
inhibitors suc h as trastuzumab. Use of trastuzumab in combination with chemotherapy has 
proved effective in improving survival in non -operable patients expressing Her -2. However, to 
date, prevalence of Her -2 expressing GC and related clinicopathological features in Braz ilian 
patients is still unknown, and the use of tyrosine kinase inhibitors is not yet adopted. The authors 
of this studies analyzed retrospectively with an immunohistochemical approach the prevalence of 
Her-2 expressing GCs, as well as correlation between Her-2 expression status and main 
clinicopathologial characteristics of GC. They have demonstrated in according with international 
data a relevant percentage of Her -2 positive GCs and thus, suggesting the appropriateness of the 
introduction of tyrosine kina se inhibitors in treatment of Her -2 positive patients with 
advanced/metastatic stage GC. The study is well conduct, however, I have some minor concerns 
that the authors should address:  
 
* I suggest adding a table summarizing data obtained from international  metanalysis that 
reported prevalence about Her -2 status in GCs and its correlation (where possible) with main 
clinicopathological features.  
 
* The paper could be improved by the addition of images of all techniques adopted for this 
study (SISH).  
 
 
 
 
 
 
 
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer re view policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant