Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  28 February 2005 Version: Date: 
 Stephan A Hahn Reviewer: 
Reviewer's report: 
General 
The study is mainly confirmatory and offers no new insights into the contribution of p16 to pancreatic 
tumorigenesis. The sequencing method (SSCP) is only a screening method and lacks sensitivity. 
Homozygous deletion (HD) analysis on non-microdissected tissues (here tissues of <90% cellularity have been used) is difficult, as 5-10% of contaminating normal tissue are likely to lead in standard 
PCRs to a positive signal, precluding a sensitive assessment of the HD status. The higher frequency 
of methylation positive tumors is in striking disagreement to previously published studies. This 
finding is not adequately discussed and could be a technical problem. At least one important study 
(Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K. M., Wilentz, R. E., Yeo, C. J., Hruban, R. H., 
and Goggins, M. Aberrant methylation of preproenkephalin and p16 genes in pancreatic 
intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol, 160: 1573-1581, 2002) reporting a 27% frequency of methylation positive pancreatic carcinoma is not referenced in the manuscript. 
In summary, the lack of novelty and the drawbacks of the methods applied precludes in my opinion 
the qualification of this manuscript for publication. 
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Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because too small an advance to publish What next?: 
 An article of insufficient interest to warrant publication in a scientific/medical Level of interest: 
journal
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  28 February 2005 Version: Date: 
 Stephan A Hahn Reviewer: 
Reviewer's report: 
General 
The study is mainly confirmatory and offers no new insights into the contribution of p16 to pancreatic 
tumorigenesis. The sequencing method (SSCP) is only a screening method and lacks sensitivity. 
Homozygous deletion (HD) analysis on non-microdissected tissues (here tissues of <90% cellularity have been used) is difficult, as 5-10% of contaminating normal tissue are likely to lead in standard 
PCRs to a positive signal, precluding a sensitive assessment of the HD status. The higher frequency 
of methylation positive tumors is in striking disagreement to previously published studies. This 
finding is not adequately discussed and could be a technical problem. At least one important study 
(Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K. M., Wilentz, R. E., Yeo, C. J., Hruban, R. H., 
and Goggins, M. Aberrant methylation of preproenkephalin and p16 genes in pancreatic 
intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol, 160: 1573-1581, 2002) reporting a 27% frequency of methylation positive pancreatic carcinoma is not referenced in the manuscript. 
In summary, the lack of novelty and the drawbacks of the methods applied precludes in my opinion 
the qualification of this manuscript for publication. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because too small an advance to publish What next?: 
 An article of insufficient interest to warrant publication in a scientific/medical Level of interest: 
journal
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  28 February 2005 Version: Date: 
 Stephan A Hahn Reviewer: 
Reviewer's report: 
General 
The study is mainly confirmatory and offers no new insights into the contribution of p16 to pancreatic 
tumorigenesis. The sequencing method (SSCP) is only a screening method and lacks sensitivity. 
Homozygous deletion (HD) analysis on non-microdissected tissues (here tissues of <90% cellularity have been used) is difficult, as 5-10% of contaminating normal tissue are likely to lead in standard 
PCRs to a positive signal, precluding a sensitive assessment of the HD status. The higher frequency 
of methylation positive tumors is in striking disagreement to previously published studies. This 
finding is not adequately discussed and could be a technical problem. At least one important study 
(Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K. M., Wilentz, R. E., Yeo, C. J., Hruban, R. H., 
and Goggins, M. Aberrant methylation of preproenkephalin and p16 genes in pancreatic 
intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol, 160: 1573-1581, 2002) reporting a 27% frequency of methylation positive pancreatic carcinoma is not referenced in the manuscript. 
In summary, the lack of novelty and the drawbacks of the methods applied precludes in my opinion 
the qualification of this manuscript for publication. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because too small an advance to publish What next?: 
 An article of insufficient interest to warrant publication in a scientific/medical Level of interest: 
journal
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
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