SUO 2018: Development of Serum MicroRNA as a Novel and Better Tumor Marker for Testicular Germ Cell Tumor than HCG and AFP

Phoenix, Arizona (UroToday.com) In this first talk by Dr. Kollmannsberger, the focus is on serum micro-RNA’s (miRNA) as a novel and potentially superior tumor marker for testicular germ cell tumors (GCTs) than HCG and AFP.

First, he started by acknowledging the limitations of the current diagnostic tools – serum tumor markers (AFP, HCG, LDH) and imaging (CT A/P).
  • Imaging: CT imaging is 70% sensitive and 60% specific. Limited by size criteria of an “abnormal node” – the larger the cutoff, the less sensitive.
  • Tumor Markers: only useful if they are expressed to begin with. Many tumors (seminoma) do not express tumor markers.
  • Not expressed in teratoma
  • False positives confuse the picture as well
By no means are these perfect tests, but they have served as the basis of management for decades!

MicroRNA’s – short (20-23 base-pairs), endogenous, single-stranded RNA molecules that regulate gene expression. Non-coding. Stable (unlike DNA). Regulate expression of various oncogenes and tumor suppressor genes. Can be measured by qPCR of serum or plasma. There are only 31 miRNAs expressed by stem cells.
In GCT setting, there are 2 clusters of miRNAs that are very specific to GCTs.
  • miR-371-373
  • miR-302
However, it should be noted that they are NOT exressed by teratoma – but are expressed by all GCT histologic subtypes.

He then reviewed the current data on miR and what makes them so promising! He focused primarily on miR371, as that has more literature supporting it.

miR371 correlates with stage and disease activity
  • Higher stage show higher levels
  • Treatment results in decreasing levels 
Rapid elimination after orchiectomy (half-life 12 hours, so reaches nadir in 48 hours)

Not expressed in teratoma

This is summarized in the slide below:
Figure 1

In his mind, there are 3 clinical scenarios with unmet need, as detailed below:
Figure 2
miR371, at least in some of the studies so far, may have begun to fill those gaps – but further studies are required.

In some of his group’s work, miR371 has served as a predictive biomarker of disease, both in CS1 relapsers and in patients with metastatic disease which has been treated:
Figure 3
(ASCO GU 2018)

In one of the most impressive slides, he notes that the AUC curve for miR371 is “almost perfect” when compared to other biomarkers for GCT:
Figure 4
These results have been repeatable and reproducible amongst independent cohorts
Correlates with the presence of viable tumor on imaging

Future trials will hopefully validate its utility prospectively.

Below are his take home points about one of the most promising new developments in testicular cancer management!
Figure 5
One such study is the SWOG S1823 study to evaluate 1175 patients with Clinical Stage 1 GCT patients.

Presented By: Christian Kollmannsberger, MD, FRCPC

Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @TjuUrology, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona
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