Biomarkers to distinguish necrosis from teratoma before pcRPLND in testicular cancer

Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) is overtreatment for metastatic non-seminomatous testicular cancer in about half the cases. Differential expression of AGR2 and KRT19 in teratoma and necrotic tissue could be used to reliably distinguish patients with teratoma from those with necrosis and reduce overtreatment.

Metastatic non-seminomatous testicular tumour patients with residual retroperitoneal tumour masses >1 cm after chemotherapy are treated with pcRPLND to remove viable tumours and teratoma, which are present in approximately 10% and 40% of cases, respectively. However, histopathology only identifies scar tissue/necrosis in up to 50%. In those patients, surgical therapy is not necessary, resulting in a relevant overtreatment. So far, no adequate pre-operative distinction between the histologies exists. Recently, the first biomarker was described with miR371a-3p in serum, which is highly specific for viable testicular germ cell tumours (GCT) but not for teratoma and/or necrosis [1].

Dr Tim Nestler (University of Cologne, Germany) presented results from a study aimed to identify mRNAs and proteins that are differentially expressed between viable tumours, teratoma, and necrosis in pcRPLND-resected cells [2]. Included were 48 patients, 16 in each histology subgroup. Representative regions were micro-dissected and subjected to mRNA analysis and a comprehensive proteomics analysis.

For the comparison of teratoma and necrosis, 84 mRNAs and 25 proteins were significantly differentially expressed. Only 2 proteins, anterior gradient 2 (AGR2) and cytokeratin 19 (KRT19), had significantly differential expressions on both levels.

“With AGR2 and KRT19, we have identified 2 proteins with their corresponding genes that are significantly and differentially expressed in the pcRPLND specimen in the clinically relevant groups teratoma and necrosis,” concluded Dr Nestler. “In perspective, these proteins could be targeted by radiolabelled 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 necrosis could be safely reduced.”

1. Diekman KP, et al. J Clin Oncol. 2019;37:1412–1423.
2. Nestler T, et al. Differentially expressed mRNA/proteins can distinguish viable germ cell tumors and teratomas from necrosis in retroperitoneal lymph node resections after chemotherapy (pcRPLND). Abstract 408, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 2022