RETRACTION WATCH & NATIONAL POST ; AMERICAN JOURNAL OF PATHOLOGY has retracted two papers by Princess Margaret Hosp Dr Silvia Lou ASA MD(Tor 77)FRCPC (Anat.Path 82) and her husband Tor Gen Hosp Internist Dr. Shereen Zarif EZZAT MD(Manitoba 84) FRCPC (Int.Med. 1990)

Retraction Watch

Tracking retractions as a window into the scientific process

Head of major diagnostic lab in Canada steps down amid investigation

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A prominent
endocrinologist pathologist has resigned from running the largest hospital diagnostic laboratory in Canada following an investigation that has uncovered evidence of falsified data in two papers, Retraction Watch has learned.
Sylvia Asa was the Program Medical Director of the Laboratory Medicine Program at the University Health Network, affiliated with the University of Toronto, until this past spring when she stepped down, according to UHN spokesperson Gillian Howard:

Our Laboratory Medicine Program has an interim Program Medical Director.  Dr. Sylvia Asa stepped down this past spring from her position as PMD.
Thank you for understanding that a legal process means that we cannot comment on any matter before the courts.

Asa, based at Princess Margaret Cancer Centre, has co-authored nearly 100 papers with Shereen Ezzat, who also works as a researcher at Princess Margaret. According to a 2007 article in a Pituitary Network Association newsletter, they are married and have worked together since 1992.
However, two of their papers are now being retracted by the American Journal of Pathology. The journal will be issuing the same note for both papers, about the genetics of breast cancer. It confirms the existence of a UHN investigation, and the presence of “falsified data” in the papers. It ends with a defense of the work by Ezzat, who asserts that the authors have “confirmed the validity and reproducibility of the findings”:

Following correspondence in September 2012 from a concerned reader regarding the May 2010 article entitled, “Genetic and Epigenetic Mechanisms Down-Regulate FGF Receptor 2 to Induce Melanoma-Associated Antigen A in Breast Cancer” by Xuegong Zhu, Sylvia L. Asa, and Shereen Ezzat (Volume 176, pages 2333e2343; http://dx.doi.org/10.2353/ajpath.2010.091049) and the December 2010 article entitled “Loss of Heterozygosity and DNA Methylation Affect Germline Fibroblast Growth Factor Receptor 4 Polymorphism to Direct Allelic Selection in Breast Cancer” by Xuegong Zhu, Lei Zheng, Sylvia L. Asa, Shereen Ezzat (Volume 177, pages 2860e2869; http://dx.doi.org/10.2353/ajpath. 2010.100509), the Editors of The American Journal of Pathology commenced an inquiry into the validity of results reported. Initial communication between the editorial office and corresponding author Dr. Ezzat failed to resolve the matter. Therefore, in March 2013 the Editors contacted University Health Network, University of Toronto (Toronto, ON, Canada), with which all authors were affiliated, and requested an investigation of the data.
The University Health Network, University of Toronto appointed an investigative committee. Dr. Christopher Paige, Vice-President of Research, University Health Network, and Dr. Charles Chan, Vice-President of Medical Affairs & Quality, University Health Network, informed the Editors in April 2015 that the articles in question contain falsified data. Specifically, in Zhu et al (Am J Pathol 176:2333e2343) Figures 1D, 2C, 4A, 4C, and 5B contain manipulated and/or fabricated data. Original source data for the published images in Figure 2C (top) were unavailable to the committee for review. In Zhu et al (Am J Pathol 177:2860e2869), Figures 1C, 4B, 5B, 5C, and 5D contain manipulated and/or fabricated data. Original source data for the published images in Figures 1C and 5C were unavailable to the committee for review. The articles are therefore being retracted from The American Journal of Pathology by the American Society for Investigative Pathology (the owner and publisher) with the concurrence of the co-authors. Dr. Ezzat states, “On behalf of all of the other authors, we wish to state that we have collectively confirmed the validity and reproducibility of the findings reported in these articles. Nevertheless, we request that these papers be retracted.”

(Due to a publisher production error, an earlier version of the notice is posted to the site, but should be fixed shortly, we understand.)
The first paper, “Genetic and Epigenetic Mechanisms Down-Regulate FGF Receptor 2 to Induce Melanoma-Associated Antigen A in Breast Cancer,” has been cited 14 times and the second, “Loss of Heterozygosity and DNA Methylation Affect Germline Fibroblast Growth Factor Receptor 4 Polymorphism to Direct Allelic Selection in Breast Cancer,” has been cited four times, according to Thomson Scientific’s Web of Knowledge.
In response to our questions about the UHN investigation, the editor in chief of the journal told us:

These concerns have been evaluated and addressed following the procedures described in the American Journal of Pathology scientific integrity policy.  The results from this process will be published in the August issue of the Journal.

Scientists have raised other questions about the couple’s research, including commenters on PubPeer who pointed out problems with several other papers authored by Asa and Ezzat.
One of those papers, in Molecular Endocrinology, issued a correction in May for a “typographical error”:

In the article “FGFR4 Polymorphic Variants Modulate Phenotypic Features of Cushing Disease” by Tae Nakano-Tateno, Toru Tateno, Maw Maw Hlaing, Lei Zheng, Katsuhiko Yoshimoto, Shozo Yamada, Sylvia L. Asa, and Shereen Ezzat (Mol Endocrinol 28:525–533, 2014; doi: 10.1210/me.2013-1412) the authors report the following typographical error in the published paper: The graphs in Figures 1B and 3, B and D, should have been labeled on the right vertical axes, as presented below. This allows a clearer appreciation that the statistical comparisons are within each group as indicated by the horizontal bars. The authors regret this error.

We’ve asked for updates on the other papers flagged by PubPeer commenters from each journal.
When contacted regarding potential issues with papers authored by Asa and Ezzat, a spokesperson for the Endocrine Society, the publisher of Molecular Endocrinology, said that they were waiting for the results of the investigation.

The Endocrine Society is cooperating with University of Toronto’s University Health Network and awaiting the results of its investigation.

We’ve called and emailed Asa and Ezzat for comment. We’re unable to find contact information for first author Xuegong Zhu. We’ll update with any response.