PSMA Expression in Differentiated Thyroid Cancer: Association With Radioiodine, 18FDG Uptake, and Patient Outcome

J Clin Endocrinol Metab. 2021 Nov 19;106(12):3536-3545. doi: 10.1210/clinem/dgab563.

Abstract

Context: Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC).

Objective: We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (18FDG) uptake, and patient outcome.

Design, setting, and patients: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center.

Main outcome measure(s): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and 18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 ± 3.7 years.

Results: Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS ≥ 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥ 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS ≥ 9) was associated with shorter progression-free survival (PFS).

Conclusions: Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.

Keywords: PSMA staining; differentiated thyroid cancer; immunohistochemistry; poorly differentiated thyroid cancer; prostate-specific membrane antigen; radioiodine-refractory.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Antigens, Surface / metabolism*
  • Biomarkers, Tumor / metabolism
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Follow-Up Studies
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Iodine Radioisotopes / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Positron Emission Tomography Computed Tomography
  • Prognosis
  • Radiopharmaceuticals / metabolism
  • Retrospective Studies
  • Survival Rate
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / mortality*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II