Vancouver Prostate Centre and SWOG AYA, Prevention and Surveillance and SWOG YI Award, Vancouver, BC, Canada
Lucia Nappi , Marisa Thi , Bernhard J. Eigl , Kim N. Chi , Martin Gleave , Alan I. So , Daniel Khalaf , Peter C. Black , Craig R. Nichols , Christian K. Kollmannsberger
Background: The pathological constitution of post-chemotherapy residual disease (PCRD) or enlarged nodes in clinical stage I (CSI) patients (pts) with germ cell tumor (GCT) is guesswork, especially when tumor markers (β-HCG, AFP, LDH) are negative. Currently, accurate assessment requires clinical follow-up with imaging to establish patterns of growth or pathological confirmation with RPLND. A blood-based approach reliably to identify patients with non teratoma viable GCT (NTVGCT) would be valuable. Methods: miR371 extracted from plasma of 44 pts with GCT was analyzed by RT-PCR and relative expression calculated by the 2-ΔΔCt method. Plasma from healthy male volunteers was used as negative control while miR-93-5p as internal positive control. The sensitivity and specificity of miR371 were calculated correlating miR371 overexpression to the presence of relapsed/residual NTVGCT. Results: Fifty eight samples (20 CSI, 20 metastatic, 18 PCRD) were analyzed. Ten CSI pts presented with suspicious enlarging nodes (≥ IIA) and miR371 was overexpressed in 5/6 pts with confirmed tumor relapse. Neither CSI pts with unconfirmed enlarging nodes (n = 4) or with no signs of relapse (n = 10) presented high miR371 levels. miR371 was overexpressed in all the pre-chemotherapy metastatic pts (n = 10) and negative after chemotherapy (n = 10), with 4 pts presenting PCRD. miR371 was negative in all the pts with PCRD and no residual NTVGCT was detected in those pts by either pathology (n = 10) or clinical follow-up (n = 8). Sensitivity and specificity were 93.3% and 100%, respectively. Conclusions: Elevated plasma levels of miR371 correlate with the presence of NTVGCT and may lead to biological rather than radiographic assessment of active GCT. Since chemotherapy is first line option for NTVGCT while is inactive in teratoma, miR371 status may be used to select pts for chemotherapy or surgery. These encouraging findings inform upcoming North American trials for further definition of miR371 operating characteristics in all stages, sites of origin, gender and age specific GCTs.
Stage | Samples (n) | Histology | miR371 + | miR 371 - | NTVGCT | |
---|---|---|---|---|---|---|
S | NS | |||||
I | 20 | 11 | 9 | 5 | 15 | 6 |
PCRD | 18 | 2 | 16 | 0 | 18 | 0 |
Metastatic | 20 | 4 | 16 | 10a | 10b | 0b |
a prechemo b postchemo
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