Abstract
Purposeα-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.MethodsWe investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.ResultsAt primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.ConclusionsThe ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.
Highlights
Germ cell cancer (GCC) is rare in the general population, it represents the most frequent malignancy in young Caucasian males, predominantly of the testis, accounting for 60% of all malignancies in these males between 20 and 40 years of age [1]
The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis
The ampTSmiR test is more sensitive than the conventional testicular germ cell cancer (TGCC) protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma
Summary
Germ cell cancer (GCC) is rare in the general population, it represents the most frequent malignancy in young Caucasian males, predominantly of the testis, accounting for 60% of all malignancies in these males between 20 and 40 years of age [1]. The 5-year survival rate of TGCC patients exceeds 96%, patients have a long term risk of developing a second primary TGCC or of progression of the disease [9] They undergo intensive and long-term follow-up after initial diagnosis, including extensive physical examination and monitoring of the levels of the conventional serum protein markers B-HCG, AFP and to a lesser extent LDH, due to its low specificity [10]. B-HCG is predominantly related to the presence of a CH component and AFP to a YST component, whereas they show little sensitivity for the detection of SE and the NS stem cell component EC This explains why a substantial percentage of TGCC patients, predominantly without CH and YST components, can be serum biomarker negative at initial diagnosis or become negative during follow-up, respectively. Our results confirm the power of elevated serum miR-371a-3p, 373-3p and 3673p levels for primary TGCC diagnosis and show the efficacy of the ampTSmiR test for TGCT relapse detection, outperforming conventional serum biomarkers
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