Author's response to reviews Title: Increased expression of Transcription Factor TFAP2 alpha correlates with chemosensitivity in advanced bladder cancer Authors:

Thank you for reviewing our manuscript entitled " Increased expression of Transcription Factor TFAP2α correlates with chemosensitivity in advanced bladder cancer " and for giving us the opportunity to submit a revised version. We have now included a 'Competing interests' section and correctly placed the Author's contributions and Acknowledgement section. We have found the comments from the reviewers very constructive and inspiring and have tried to address all points in the revised manuscript. The manuscript was corrected for language and the abstract section has been reformulated. We hope you will find the manuscript suitable for publication in BMC Cancer. Reviewer's report: Overall this paper by Nordentoft and colleagues attempts to understand chemosensitivity in advanced bladder cancer by studying the expression of a transcription factor known as TFAP2 alpha. Since response rates to cisplatin based chemotherapy are only about 50%, this is an important area of study. However, this paper was somewhat difficult to follow. Major compulsory Revisions 1. Introduction Page 3, Line 3: Further details should be provided about the other predictive markers BIRC5 and BSG. We have added further details about this and we now write: "BIRC5 (survivin) and BSG (emmprin) were validated by immunohistochemistry in an independent material of 124 patients with locally advanced (T 4b and N 2-3) or metastatic (M 1) disease receiving cisplatin-containing therapy as independent predictive markers for response and survival after cisplatin-containing chemotherapy " Reviewer: 2. Discussion a)Line 4: There needs to be discussion as to why high levels of TFAP2alpha protein expression predict a better outcome in lymph node invasive dz vs. non-lymph node invasive subgroup. For example, other than actual involvement of the lymph nodes are there other molecular differences known to exist between lymph node+ and negative cancers that could explain this? Specifically with respect to to p53/p21? b)There is a fair amount of information about other cancers, as opposed to a more detailed discussion about bladder cancer itself. c)There should be some discussion about future directions of this research, and how these results could be further validated. a)We added the following sections to the discussion: 1 Interestingly, node positive colorectal cancers showed significant losses for p21 and E-cadherin compared to node negative cancer. TFAP2α directly binds to the promoter of E-cadherin, where it has been previously reported to act as a transcriptional activator. High E-cadherin expression has been reported to increase cisplatinand gemcitabine sensitivity in pancreatic cancer. 2 In …