Reviewer's report
Title:Heterogeneity of Amplification of HER2, EGFR, CCND1 and MYC in
Gastric Cancer
Version:2Date:28 October 2014
Reviewer: Claudio Luchini
Reviewer's report:
Reviewer’s report
MINOR ESSENTIAL REVISIONS
1. Page 5th, 1st-3rd row. In the Literature, tumor genetic heterogeneity is NOT
rarely analyzed in systematic studies. I suggest to change the phrase starting
with “Nevertheless” with this phrase: “Nevertheless, even in many relevant
cancer types and for highly promising diagnostic and therapeutic molecules,
intratumor genetic heterogeneity is not analyzed in systematic studies as well as
its importance could require”. In other sections of this paper this concept is
already well expressed.
2. Page 5th, 22nd row: The average number of tumor containing blocks was 3.7
(range: 1-9). How can the authors explain that some cases have only one block
from a gastrectomy with tumor? Small tumors? Under-sampling? This passage
could influence the search of tumor heterogeneity and has to be clarified in this
point.
3. Page 6th, 5-6th row: multiple punches were taken from one or several tumor
blocks: have the Authors made the selection of these blocks random or on the
basis of histopathologic and/or of morphological criteria?
4. Page 9th, 14th row: I suggest to put a picture even for the
immunohistochemistry and not only for FISH. In this way even the clinical doctors
can familiarize with this kind of analysis, well-known above all by pathologists.
5. Page 11th, 6th row: please change “Heterogeneous” with “heterogeneous”.
6. Page 12th, 4th row: “….TMA analysis of one sample each from nine different
tumor-containing blocks…”. But the range of the blocks was 1-9, so I think this
passage has to be changed, writing that the blocks are not always 9.
7. Page 12th, 14th row: “HER2 was found amplified in 19 of 109 cancers,
including 16 cancers with 3+ positivity by IHC at least in one TMA spot”. In the
paper you have always put the percentage to describe the results for other
genes, so please put the percentage even in this point. I suggest: “HER2 was
found amplified in 19 of 109 (17,4%) cancers, including 16 cancers with 3+
positivity by IHC at least in one TMA spot”.
8. Page 13th, 15th row: the subject of the sentence is “interrelation”, so you have
to change “highlight” with “highlights”.
DISCRETIONARY REVISIONS
1. Page 3rd, 15-16th row: maybe it could be a good idea to put between brackets
the percentages. I suggest: “Intra-tumor heterogeneity was found in the primary
tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with
CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.1%) cancers with
MYC amplification.” I think that the information has to be immediately
understandable, above all in the abstract. In the paper the percentages are
present.
2. Page 4th, 18th row: I suggest to remove the first comma, between “advantage”
and “that”: in this way the phrase is more fluent.
3. Page 4th, 25th row: I suggest to put “small biopsy material” and remove “a
biopsy”. Small biopsy material is more descriptive and more appropriate in
comparison to “a biopsy” to indicate this type of specimen.
4. Page 5th, 4th row. I suggest to change the present phrase with this more
fluent phrase: ”Thus, the aim of our study was to deepen genomic heterogeneity
in gastric cancer in a larger scale”.
5. Page 5th, 11th row: I suggested to put “are sampled” at the end of the phrase.
6. Page 12th, 25th row: I suggest to remove the comma between “drawback” and
“that”.
7. Page 12th, 26th row: I suggest to put a comma between “areas” and “and”.
8. Page 13th, 10th row: I suggest to remove the comma between “question” and
“whether”.
9. Page 14th, 7th row: I suggest to remove the comma between “unclear” and
“to”.
10. Page 14th, 10th row: I suggest to change “fit well” with “fit very well” better to
distinguish the results of EGFR to the results of HER2, for which you have written
the same “fit well”.
11. Page 15th, 3rd row: I suggest to put between brackets the phrase “a
monoclonal antibody to EGFR”.
12. Page 16th, 5th row: I suggest to put a comma between “Markedly” and
“higher”.
13. Page 17th, 9th row: I suggest to change the word “findings” with “conclusion”
for semantic reasons.
14. Page 17th, 22nd row: I suggest to change “are rare but exist” with “are rare
but represent an existing category: they may open new
therapy……………………….”.
15. For all the tables: check this sentence, that is present in all the tables: “Bold
black outline in the “metastases spots” highlight spots……………………”. Is
correct highlight or is correct “highlights”?
Level of interest: An article of importance in its field
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
Reviewer's report
Title:Heterogeneity of Amplification of HER2, EGFR, CCND1 and MYC in
Gastric Cancer
Version:2Date:28 October 2014
Reviewer: Claudio Luchini
Reviewer's report:
Reviewer’s report
MINOR ESSENTIAL REVISIONS
1. Page 5th, 1st-3rd row. In the Literature, tumor genetic heterogeneity is NOT
rarely analyzed in systematic studies. I suggest to change the phrase starting
with “Nevertheless” with this phrase: “Nevertheless, even in many relevant
cancer types and for highly promising diagnostic and therapeutic molecules,
intratumor genetic heterogeneity is not analyzed in systematic studies as well as
its importance could require”. In other sections of this paper this concept is
already well expressed.
2. Page 5th, 22nd row: The average number of tumor containing blocks was 3.7
(range: 1-9). How can the authors explain that some cases have only one block
from a gastrectomy with tumor? Small tumors? Under-sampling? This passage
could influence the search of tumor heterogeneity and has to be clarified in this
point.
3. Page 6th, 5-6th row: multiple punches were taken from one or several tumor
blocks: have the Authors made the selection of these blocks random or on the
basis of histopathologic and/or of morphological criteria?
4. Page 9th, 14th row: I suggest to put a picture even for the
immunohistochemistry and not only for FISH. In this way even the clinical doctors
can familiarize with this kind of analysis, well-known above all by pathologists.
5. Page 11th, 6th row: please change “Heterogeneous” with “heterogeneous”.
6. Page 12th, 4th row: “….TMA analysis of one sample each from nine different
tumor-containing blocks…”. But the range of the blocks was 1-9, so I think this
passage has to be changed, writing that the blocks are not always 9.
7. Page 12th, 14th row: “HER2 was found amplified in 19 of 109 cancers,
including 16 cancers with 3+ positivity by IHC at least in one TMA spot”. In the
paper you have always put the percentage to describe the results for other
genes, so please put the percentage even in this point. I suggest: “HER2 was
found amplified in 19 of 109 (17,4%) cancers, including 16 cancers with 3+
positivity by IHC at least in one TMA spot”.
8. Page 13th, 15th row: the subject of the sentence is “interrelation”, so you have
to change “highlight” with “highlights”.
DISCRETIONARY REVISIONS
1. Page 3rd, 15-16th row: maybe it could be a good idea to put between brackets
the percentages. I suggest: “Intra-tumor heterogeneity was found in the primary
tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with
CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.1%) cancers with
MYC amplification.” I think that the information has to be immediately
understandable, above all in the abstract. In the paper the percentages are
present.
2. Page 4th, 18th row: I suggest to remove the first comma, between “advantage”
and “that”: in this way the phrase is more fluent.
3. Page 4th, 25th row: I suggest to put “small biopsy material” and remove “a
biopsy”. Small biopsy material is more descriptive and more appropriate in
comparison to “a biopsy” to indicate this type of specimen.
4. Page 5th, 4th row. I suggest to change the present phrase with this more
fluent phrase: ”Thus, the aim of our study was to deepen genomic heterogeneity
in gastric cancer in a larger scale”.
5. Page 5th, 11th row: I suggested to put “are sampled” at the end of the phrase.
6. Page 12th, 25th row: I suggest to remove the comma between “drawback” and
“that”.
7. Page 12th, 26th row: I suggest to put a comma between “areas” and “and”.
8. Page 13th, 10th row: I suggest to remove the comma between “question” and
“whether”.
9. Page 14th, 7th row: I suggest to remove the comma between “unclear” and
“to”.
10. Page 14th, 10th row: I suggest to change “fit well” with “fit very well” better to
distinguish the results of EGFR to the results of HER2, for which you have written
the same “fit well”.
11. Page 15th, 3rd row: I suggest to put between brackets the phrase “a
monoclonal antibody to EGFR”.
12. Page 16th, 5th row: I suggest to put a comma between “Markedly” and
“higher”.
13. Page 17th, 9th row: I suggest to change the word “findings” with “conclusion”
for semantic reasons.
14. Page 17th, 22nd row: I suggest to change “are rare but exist” with “are rare
but represent an existing category: they may open new
therapy……………………….”.
15. For all the tables: check this sentence, that is present in all the tables: “Bold
black outline in the “metastases spots” highlight spots……………………”. Is
correct highlight or is correct “highlights”?
Level of interest: An article of importance in its field
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
Please review this paper.
user
Reviewer's report
Title:Heterogeneity of Amplification of HER2, EGFR, CCND1 and MYC in
Gastric Cancer
Version:2Date:28 October 2014
Reviewer: Claudio Luchini
Reviewer's report:
Reviewer’s report
MINOR ESSENTIAL REVISIONS
1. Page 5th, 1st-3rd row. In the Literature, tumor genetic heterogeneity is NOT
rarely analyzed in systematic studies. I suggest to change the phrase starting
with “Nevertheless” with this phrase: “Nevertheless, even in many relevant
cancer types and for highly promising diagnostic and therapeutic molecules,
intratumor genetic heterogeneity is not analyzed in systematic studies as well as
its importance could require”. In other sections of this paper this concept is
already well expressed.
2. Page 5th, 22nd row: The average number of tumor containing blocks was 3.7
(range: 1-9). How can the authors explain that some cases have only one block
from a gastrectomy with tumor? Small tumors? Under-sampling? This passage
could influence the search of tumor heterogeneity and has to be clarified in this
point.
3. Page 6th, 5-6th row: multiple punches were taken from one or several tumor
blocks: have the Authors made the selection of these blocks random or on the
basis of histopathologic and/or of morphological criteria?
4. Page 9th, 14th row: I suggest to put a picture even for the
immunohistochemistry and not only for FISH. In this way even the clinical doctors
can familiarize with this kind of analysis, well-known above all by pathologists.
5. Page 11th, 6th row: please change “Heterogeneous” with “heterogeneous”.
6. Page 12th, 4th row: “….TMA analysis of one sample each from nine different
tumor-containing blocks…”. But the range of the blocks was 1-9, so I think this
passage has to be changed, writing that the blocks are not always 9.
7. Page 12th, 14th row: “HER2 was found amplified in 19 of 109 cancers,
including 16 cancers with 3+ positivity by IHC at least in one TMA spot”. In the
paper you have always put the percentage to describe the results for other
genes, so please put the percentage even in this point. I suggest: “HER2 was
found amplified in 19 of 109 (17,4%) cancers, including 16 cancers with 3+
positivity by IHC at least in one TMA spot”.
8. Page 13th, 15th row: the subject of the sentence is “interrelation”, so you have
to change “highlight” with “highlights”.
DISCRETIONARY REVISIONS
1. Page 3rd, 15-16th row: maybe it could be a good idea to put between brackets
the percentages. I suggest: “Intra-tumor heterogeneity was found in the primary
tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with
CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.1%) cancers with
MYC amplification.” I think that the information has to be immediately
understandable, above all in the abstract. In the paper the percentages are
present.
2. Page 4th, 18th row: I suggest to remove the first comma, between “advantage”
and “that”: in this way the phrase is more fluent.
3. Page 4th, 25th row: I suggest to put “small biopsy material” and remove “a
biopsy”. Small biopsy material is more descriptive and more appropriate in
comparison to “a biopsy” to indicate this type of specimen.
4. Page 5th, 4th row. I suggest to change the present phrase with this more
fluent phrase: ”Thus, the aim of our study was to deepen genomic heterogeneity
in gastric cancer in a larger scale”.
5. Page 5th, 11th row: I suggested to put “are sampled” at the end of the phrase.
6. Page 12th, 25th row: I suggest to remove the comma between “drawback” and
“that”.
7. Page 12th, 26th row: I suggest to put a comma between “areas” and “and”.
8. Page 13th, 10th row: I suggest to remove the comma between “question” and
“whether”.
9. Page 14th, 7th row: I suggest to remove the comma between “unclear” and
“to”.
10. Page 14th, 10th row: I suggest to change “fit well” with “fit very well” better to
distinguish the results of EGFR to the results of HER2, for which you have written
the same “fit well”.
11. Page 15th, 3rd row: I suggest to put between brackets the phrase “a
monoclonal antibody to EGFR”.
12. Page 16th, 5th row: I suggest to put a comma between “Markedly” and
“higher”.
13. Page 17th, 9th row: I suggest to change the word “findings” with “conclusion”
for semantic reasons.
14. Page 17th, 22nd row: I suggest to change “are rare but exist” with “are rare
but represent an existing category: they may open new
therapy……………………….”.
15. For all the tables: check this sentence, that is present in all the tables: “Bold
black outline in the “metastases spots” highlight spots……………………”. Is
correct highlight or is correct “highlights”?
Level of interest: An article of importance in its field
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
assistant