TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities

Virchows Arch. 2024 Nov;485(5):815-828. doi: 10.1007/s00428-024-03926-1. Epub 2024 Oct 8.

Abstract

Thyroid transcription factor 1 (TTF-1) immunohistochemistry (IHC) is routinely used for the distinction of primary pulmonary adenocarcinomas. However, TTF-1 can also occur in other malignancies. A tissue microarray containing 17,772 samples from 152 different tumor types was analyzed. Napsin-A, CK20, SATB2, FABP1, and Villin-1 IHC data were available from previous studies. TTF-1 staining was seen in 82 of 152 tumor categories including thyroidal cancers (19-100%), adenocarcinomas (94%), neuroendocrine tumors (67%) of the lung, small cell neuroendocrine carcinomas (71-80%), mesenchymal tumors (up to 42%), and thymomas (39%). Comparative analysis of TTF-1 and Napsin-A revealed a sensitivity/specificity of 94%/86% (TTF-1), 87%/98% (Napsin-A), and 85%/99.1% (TTF-1 and Napsin-A) for the distinction of pulmonary adenocarcinomas. Combined analysis of TTF-1 and enteric markers revealed a positivity for TTF-1 and at least one enteric marker in 22% of pulmonary adenocarcinomas but also a TTF-1 positivity in 6% of colorectal, 2% of pancreatic, and 3% of gastric adenocarcinomas. TTF-1 is a marker of high sensitivity but insufficient specificity for pulmonary adenocarcinomas. A small fraction of TTF-1-positive gastrointestinal adenocarcinomas represents a pitfall mimicking enteric-type pulmonary adenocarcinoma. Combined analysis of TTF-1 and Napsin-A improves the specificity of pulmonary adenocarcinoma diagnosis.

Keywords: Diagnosis; Immunohistochemistry; Pulmonary adenocarcinomas; TTF-1; Tissue microarray.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aspartic Acid Endopeptidases
  • Biomarkers, Tumor* / analysis
  • Humans
  • Immunohistochemistry*
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism
  • Sensitivity and Specificity*
  • Thyroid Neoplasms* / diagnosis
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology
  • Thyroid Nuclear Factor 1* / analysis
  • Thyroid Nuclear Factor 1* / metabolism
  • Tissue Array Analysis*
  • Transcription Factors* / analysis
  • Transcription Factors* / metabolism

Substances

  • Biomarkers, Tumor
  • Transcription Factors
  • Thyroid Nuclear Factor 1
  • NKX2-1 protein, human
  • NAPSA protein, human
  • Nuclear Proteins
  • Aspartic Acid Endopeptidases