Validation of AGR2 and KRT19 as specific proteins being significantly and differentially expressed in teratoma compared to necrosis in retroperitoneal lymph node resections after chemotherapy (pcRPLND).

Authors

null

Tim Nestler

Department of Urology, University Hospital of Cologne, Cologne, Germany

Tim Nestler , Lara Kremer , Melanie von Brandenstein , Maike Wittersheim , Svenja Wagener-Ryczek , Pia Paffenholz , Stefan Mueller , Alexander Quaas , Martin Hellmich , Margarete Odenthal , David Pfister , Axel Heidenreich

Organizations

Department of Urology, University Hospital of Cologne, Cologne, Germany, Institute of Pathology, University Hospital of Cologne, Cologne, Germany, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany, Institute of Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany

Research Funding

Other
Research Grant by the German Department of Defense

Background: Metastatic non-seminomatous testicular tumor patients with residual retroperitoneal tumor masses > 1cm after chemotherapy are treated with pcRPLND. The goal of pcRPLND is to remove viable tumors (V) and teratoma (T), which are present in approximately 10% and 40% of cases, respectively. However, histopathologically, only scar/necrosis (N) is identified in the remaining 50% of patients. In those patients, surgical therapy is not necessary, resulting in a relevant overtreatment. So far, no adequate distinction between the histologies exists preoperatively. Recently, the first biomarker was described with miR371a-3p in serum, which is highly specific for V, but not for T. In 2022 we reported AGR2 and KRT19 to be significantly and differentially expressed in teratoma compared to necrosis in pcRPLND tissue on protein and mRNA level. The aim of this study was to validate these proteins on an independent cohort. Methods: All consecutive pcRPLND patients from 2021 who were treated in the University Hospital of Cologne, Germany, were selected (n=66). All patients had residual masses > 1 cm and normalized or plateaued tumor markers. For immunohistochemistry, the monoclonal antibodies KRT19 and AGR2 were applied to representative Formalin-Fixed Paraffin-Embedded tissue. To quantify the results, the H-score was used. The investigators were blinded to the final pathohistological results. Results: The cohort was composed of 66 patients, 23 patients with T, 24 patients with V and 19 patients with N. Significantly higher H-scores were shown for AGR2 and KRT19 when comparing T vs. N and T vs. V (both p < 0.0001). The discriminatory ability of the two proteins AGR2 and KRT19 was calculated by AUCs for T vs. N and was 1.0 in each case with a corresponding sensitivity and specificity for T of 100%. Conclusions: With AGR2 and KRT19, we could validate the two proteins that are significantly and differentially expressed in the pcRPLND specimen in the clinically relevant groups T vs. N. In perspective, these proteins could be targeted by radiolabeled ligands as a tracer in order to reliably distinguish patients with teratoma from those with necrosis by means of functional imaging. Thus, overtreatment with pcRPLND of patients with N could be safely reduced.

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer,Urethral Cancer

Sub Track

Diagnostics and Imaging

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 412)

DOI

10.1200/JCO.2023.41.6_suppl.412

Abstract #

412

Poster Bd #

L14

Abstract Disclosures