title: The search for biomarkers of metastatic seminoma.
abstract: OBJECTIVE
  We screened 90 potential parameters as biomarkers of metastatic seminoma to facilitate detection and eliminate unnecessary therapeutic or diagnostic efforts.
  
  
  METHODS
  A total of 527 men with pure seminoma (diagnosed 2000 to 2011) were followed during therapy. More than 90 demographic/anamnestic (eg age, height, weight) histopathological parameters (testicular/tumor size, testicular intraepithelial neoplasia) and levels of tumor markers (eg α-fetoprotein, β-human chorionic gonadotropin, lactate dehydrogenase) in peripheral blood and testicular vein were collected for analysis via logistic regression. Previously described risk factors (tumors larger than 4 cm, infiltration of rete testis) were assessed separately.
  
  
  RESULTS
  Established parameters such as tumor length (p = 0.0003), involvement of lymphatic (p <0.0001) or vascular channels (p = 0.0009), extent of primary tumor (p <0.0001) and infiltration of the tunica albuginea (p = 0.02) as well as new biomarkers such as absence of testicular intraepithelial neoplasia in tumor bearing testis (p = 0.03), testicular volume (p = 0.04) and tumor volume (p = 0.02) showed a significant association with metastatic disease. This association was also true of lactate dehydrogenase, human chorionic gonadotropin and α-fetoprotein (p <0.0001 at maximum). However, the discriminatory capacity of these biomarkers (concordance or ROC area) did not exceed 65% when examined alone or in combination, and higher values (up to 80%) were detected for enzyme levels. A subset of metastatic seminoma (2% to 27%) was detectable with high accuracy (positive predictive value 92% to 100%) based on enzyme measurements (p <0.0006).
  
  
  CONCLUSIONS
  New biomarkers of metastatic seminoma were identified and previously described risk factors were validated. Further prospective studies of these novel parameters are warranted to verify our findings and to explore a potential use for detecting occult metastases.
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Hamburg, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Ruf
authors.forename: N
authors.initials: N
authors.lastname: Khalili-Harbi
authors.forename: S
authors.initials: S
authors.lastname: Sachs
authors.forename: H
authors.initials: H
authors.lastname: Isbarn
authors.forename: W
authors.initials: W
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Matthies
authors.forename: V
authors.initials: V
authors.lastname: Meineke
authors.forename: M
authors.initials: M
authors.lastname: Fisch
authors.forename: F K
authors.initials: FK
authors.lastname: Chun
authors.forename: M
authors.initials: M
authors.lastname: Abend
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods; D016001:Confidence Intervals; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D018239:Seminoma / Q000097:blood / Q000556:secondary* / Q000628:therapy; D013736:Testicular Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy; D016896:Treatment Outcome; D047368:Tumor Burden; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; D007770:L-Lactate Dehydrogenase
keywords: AFP; HCG; LDH; LH; PLAP; TIN; cS; clinical stage; human chorionic gonadotropin; lactate dehydrogenase; luteinizing hormone; neoplasm metastasis; placental alkaline phosphatase; seminoma; testicular intraepithelial neoplasia; testicular neoplasms; tumor burden; α-fetoprotein