Alpha-fetoprotein (AFP) is the Marker that Distinguishes Non-seminoma from Seminoma
Alpha-fetoprotein (AFP) is the definitive marker that distinguishes non-seminomatous germ cell tumors from pure seminomas, as seminoma cells do not produce AFP. 1
Tumor Marker Characteristics in Germ Cell Tumors
AFP in Seminoma vs. Non-seminoma
- AFP is exclusively produced by non-seminomatous germ cell tumors (NSGCTs) 1
- Pure seminomas do not produce AFP; any elevation above normal range indicates presence of non-seminomatous elements 1, 2
- The presence of AFP in a patient with presumed seminoma contradicts the diagnosis of pure seminoma and indicates a non-seminomatous component 3
Other Tumor Markers
- Human chorionic gonadotropin (hCG) can be elevated in both seminomas and non-seminomas 1
- Lactate dehydrogenase (LDH) can be elevated in both seminoma and non-seminoma 1
- AFP has a half-life of 5-7 days 1
Clinical Applications
Diagnostic Implications
- When evaluating a testicular mass, AFP elevation definitively rules out pure seminoma 1, 2
- AFP levels up to 200 IU/L may correlate with pure seminoma, but extremely high levels suggest non-seminomatous elements 3
- According to ASCO guidelines, serum markers should be measured before and after orchiectomy 1
Staging and Risk Assessment
- The IGCCCG risk classification incorporates serum marker values for staging metastatic disease 1
- For non-seminomas, AFP, hCG, and LDH should be measured before and after orchiectomy and before chemotherapy 1
- For seminomas with preorchiectomy elevations, hCG and LDH should be measured postorchiectomy 1
Monitoring
- AFP and hCG should be monitored every 3-4 months for the first 3 years, every 6 months for years 4-7, and annually thereafter 4
- Rising AFP after treatment indicates disease progression or recurrence 4
Pitfalls and Caveats
- Some studies have detected AFP mRNA in seminomas using highly sensitive techniques (RT-PCR), suggesting potential for differentiation into non-seminomatous elements 5
- Approximately 23% of non-seminomas may have neither AFP nor hCG elevation in tumor tissue or serum 2
- False elevations of AFP can occur in liver disease and other non-malignant conditions 1
- Placental alkaline phosphatase (PLAP) has been investigated as a marker for seminoma but is not as specific as AFP is for non-seminoma 6
In conclusion, when distinguishing between seminoma and non-seminoma, AFP is the definitive marker, as its elevation conclusively indicates the presence of non-seminomatous elements, while hCG and LDH can be elevated in both types of germ cell tumors.