Inhibin Alpha Expression in Human Tumors: A Tissue Microarray Study on 12,212 Tumors
, Viktor Reiswich 1, David Dum 1, Anne Menz 1, Viktoria Chirico 1, Claudia Hube-Magg 1, Christoph Fraune 1, Ahmed Abdulwahab Bawahab 1,2, Christian Bernreuther 1, Ronald Simon 1,*, Till S. Clauditz 1, Guido Sauter 1, Andrea Hinsch 1, Simon Kind 1, Frank Jacobsen 1, Stefan Steurer 1, Sarah Minner 1, Eike Burandt 1, add
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Round 1
Reviewer 1 Report
Michael and co-workers detected inhibin alpha expression in a tissue microarray containing 15012 samples from 134 different tumor types and subtypes. The results showed that INHA positivity in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex- cord stroma tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas and 44% of carcinomas of the adrenal cortex, and in 46.7% of 15 pancreatic acinar cell carcinomas. An at least weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. All these results are important and helpful to understand the inhibin alpha expression in tumor tissue for tumor diagnostic. However, there are some issues need to be addressed.
1, The author should expand the introduction and clearly and amply expand the background for detection of inhibin alpha expression in the tumor tissue. The author should highlight the importance of detection the inhibin alpha in multiple tumor samples, the advantage for the tumor microarray.
2, The author should show the scale bar in the Figures 1 and 2.
3, The INHA positive was also seen in normal tissues, is that mean the alpha-inhibin is not specific for the tumor cells. The corresponding H&E staining is necessary for comparison. Or the author should demonstrate the specific of the tumor cells
4, The author should separate the data from previous literature and the data in these studies in Figure 3. In addition, the author should cite the previous literature.
5, the author should describe the TMA manufacturing process in the manuscript. It will be convenient to help readers to understand the method.
How the author get the tissue spot smaller as 0.6 mm? how to transmit hundreds samples into one slide one time? How to get the images?
Author Response
Dear Reviewer,
Please find enclosed our revised manuscript entitled „Inhibin alpha expression in human tumors: A tissue microarray study on 12,223 tumors.”.
We would like to thank the reviewers for their comments on how to improve the manuscript. Please find below our point-by-point responses to all reviewers’ comments.
In reply to reviewer #1:
Michael and co-workers detected inhibin alpha expression in a tissue microarray containing 15012 samples from 134 different tumor types and subtypes. The results showed that INHA positivity in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex- cord stroma tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas and 44% of carcinomas of the adrenal cortex, and in 46.7% of 15 pancreatic acinar cell carcinomas. An at least weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. All these results are important and helpful to understand the inhibin alpha expression in tumor tissue for tumor diagnostic. However, there are some issues need to be addressed.
1, The author should expand the introduction and clearly and amply expand the background for detection of inhibin alpha expression in the tumor tissue. The author should highlight the importance of detection the inhibin alpha in multiple tumor samples, the advantage for the tumor microarray.
Reply: We have now better described the reasons prompting for our analysis in the introduction, lines 43-47.
2, The author should show the scale bar in the Figures 1 and 2.
Reply: We have added scale bars to Figures 1 and 2.
3, The INHA positive was also seen in normal tissues, is that mean the alpha-inhibin is not specific for the tumor cells. The corresponding H&E staining is necessary for comparison. Or the author should demonstrate the specific of the tumor cells
Reply: We have now explained that the slides were analyzed by an experienced pathologist and that HE stained sections were used for comparison (page 2, lines 93-95).
4, The author should separate the data from previous literature and the data in these studies in Figure 3. In addition, the author should cite the previous literature.
Reply: The data from this study are represented by the “+” sign in Figure 3. Following the reveiwer’s suggestion, we have collected the literature and raw data corresponding to Figure 3 in supplement table 1.
5, the author should describe the TMA manufacturing process in the manuscript. It will be convenient to help readers to understand the method. How the author get the tissue spot smaller as 0.6 mm? how to transmit hundreds samples into one slide one time? How to get the images?
Reply: We now better explained that there was not one huge TMA block but a set of 48 “regular” TMA blocks containing all these cancers (page 2, lines 67-69).
We are grateful for the time and effort taken to review our manuscript.
With kind regards,
On behalf of the authors
Ronald Simon
Author Response File: 
Author Response.doc
Reviewer 2 Report
In this study, Soren et al. did a comprehensive study to characterize the tissue/tumor type distribution of INHA expression. The authors have collected a unique resources. But, I feel this unique dataset has not been utilized to its full potential. The paper was written in a clear and logical manner, and the analysis and discussion are thorough. However, from the personal viewpoint of the reviewers, there are 2 points that could be improved.
1, Demographic information on patient cohort is quite deficient.
2, the authors are sugguested that build a website with summary information, original images and annotation information. This will be very helpful for research community.
Author Response
Dear Reviewer,
Please find enclosed our revised manuscript entitled „Inhibin alpha expression in human tumors: A tissue microarray study on 12,223 tumors.”.
We would like to thank the reviewers for their comments on how to improve the manuscript. Please find below our point-by-point responses to all reviewers’ comments.
In reply to reviewer #2:
In this study, Soren et al. did a comprehensive study to characterize the tissue/tumor type distribution of INHA expression. The authors have collected a unique resources. But, I feel this unique dataset has not been utilized to its full potential. The paper was written in a clear and logical manner, and the analysis and discussion are thorough. However, from the personal viewpoint of the reviewers, there are 2 points that could be improved.
1, Demographic information on patient cohort is quite deficient.
Reply: We have now added the available demographic data on page 2, lines 66-68.
2, the authors are suggested that build a website with summary information, original images and annotation information. This will be very helpful for research community.
Reply: We agreed that result summaries and example images will be displayed on the antibody vendor’s website (see https://ms-validatedantibodies.com) once the study is published.
We are grateful for the time and effort taken to review our manuscript.
With kind regards,
On behalf of the authors
Ronald Simon
Author Response File: Author Response.doc
