cytoplasmic positivity of TTF-1

eIHC

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

Tumors

 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).