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cytoplasmic positivity of TTF-1

Wednesday 22 May 2013

cytoplasmic positivity of TTF1


Cytoplasmic staining with TTF-1 has been little studied. This cytoplasmic staining is due to a cross-reacting antigen of 160 kd, which is not an alternative splicing product of TTF-115.

In a large series of consecutive cases, about 6% (23/361) of all tumours from a variety of sites showed cytoplasmic staining.

- hepatocellular carcinoma
- a minority of pulmonary adenocarcinomas show coarse granular cytoplasmic staining
- occasionally in squamous carcinomas of the lung, head, neck and cervix
- occasional positivity in oncocytic thyroid tumours
- some gastrointestinal and pancreatic carcinoids
- colonic adenocarcinoma
- rather commonly in decalcified bone

- perinuclear staining in :

  • small and large intestine
  • pancreatic ductal and acinar cells


- hepatocellular carcinoma

  • The binding of both thyroid transcription factor-1 and HepPar1 is to mitochondrial proteins in hepatocytes.
  • The staining is usually granular.
  • Staining is seen with a biotin-free protocol8, although several authors used a biotin-based system in combination with HIER: false perinuclear positivity due to endogenous biotin may sometimes appear.
  • The diffuse cytoplasmic staining of hepatocytes (and hepatocellular carcinoma) is seen only with clone 8G7G3/1 (DakoCytomation and others), not with clone SPT24 (NovoCastra).