TROP-2 immunohistochemistry: a highly accurate method in the differential diagnosis of papillary thyroid carcinoma

Pathology. 2016 Aug;48(5):425-33. doi: 10.1016/j.pathol.2016.04.002. Epub 2016 Jun 14.

Abstract

We aimed to evaluate the diagnostic utility of the novel immunohistochemical marker TROP-2 on thyroid specimens (226 tumours and 207 controls). Whole slide immunohistochemistry was performed and scored by automated digital image analysis. Non-neoplastic thyroid, follicular adenomas, follicular carcinomas, and medullary carcinomas were negative for TROP-2 immunostaining. The majority of papillary thyroid carcinoma (PTC) specimens (94/114, 82.5%) were positive for TROP-2; however, the pattern of staining differed significantly between the histopathological variants. All papillary microcarcinomas (mPTC), PTC classic variant (PTC cv), and tall cell variant (PTC tcv) were TROP-2 positive, with mainly diffuse staining. In contrast, less than half of the PTC follicular variant specimens were positive for TROP-2, with only focal immunoreactivity. TROP-2 could identify PTC cv with 98.1% sensitivity and 97.5% specificity. ROC curve analysis found that the presence of >10% of TROP-2 positive cells in a tumour supported a diagnosis of PTC. The study of intratumoural heterogeneity showed that low-volume cytological samples of PTC cv could be adequately assessed by TROP-2 immunostaining. The TROP-2 H-score (intensity multiplied by proportion) was significantly associated with PTC variant and capsular invasion in encapsulated PTC follicular variant (p<0.001). None of the baseline (age, gender) and clinical (tumour size, nodal disease, stage) parameters were correlated with TROP-2 expression. In conclusion, TROP-2 membranous staining is a very sensitive and specific marker for PTC cv, PTC tcv, and mPTC, with high overall specificity for PTC.

Keywords: TROP-2; automated image analysis; differential diagnosis; immunohistochemistry; papillary thyroid carcinoma; thyroid.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / biosynthesis*
  • Area Under Curve
  • Biomarkers, Tumor / analysis*
  • Carcinoma / diagnosis*
  • Carcinoma, Papillary
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / biosynthesis*
  • Child
  • Diagnosis, Differential
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Immunohistochemistry
  • Male
  • Middle Aged
  • ROC Curve
  • Sensitivity and Specificity
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis*
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • TACSTD2 protein, human