Prognostic significance of β-human chorionic gonadotropin and PAX8 expression in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy with a median survival of five months. Multimodality treatment is associated with some improvement in survival, but patients are only infrequently curable. Although β-hCG secretion has been reported in many neoplasms, it has never been described in ATC. The objectives of this study were to report a case of β-hCG-secreting ATC and to study the expression and significance of β-hCG and PAX8 in an institutional cohort of ATC.

The sentinel case was characterized and then immunohistochemistry was performed for β-hCG and PAX8 on 30 ATC patients. Clinical follow-up was obtained by chart review.

The sentinel patient with β-hCG-secreting ATC had a dramatic response to chemotherapy and radiation. After surgical excision of residual disease, the patient developed a regional recurrence of differentiated thyroid carcinoma at 18 months. However, she is now, 30 months after initial therapy, with no evidence of disease and no detectable serum β-hCG or thyroglobulin. Five of the 30 (17%) total ATCs were positive for β-hCG and 18 (60%) for PAX8. Outcomes for the β-hCG-positive cases were not significantly different from those for negative ones. However, none of the other four β-hCG-positive ATC patients received treatment with either chemotherapy or radiation. Interestingly, PAX8 positivity correlated with statistically significantly better overall survival (p=0.019).

β-hCG is expressed in a minority of ATCs. Although only a single case in the study had diffuse immunohistochemical expression, the response it showed to aggressive multimodality therapy and the resulting favorable outcome suggest that β-hCG-positive ATC may be a unique tumor subtype, or possibly even a unique entity. PAX8 is a useful marker of ATC and may be helpful in the differential diagnosis with other malignant neoplasms.