TTF-1 is a member of the NKX2 family of homeodomain transcription factors found in epithelial cells of the thyroid gland and lung. TTF-1 has been shown to stain approximately 65-70% of cases of lung adenocarcinomas (ADC), with a small number of cases of lung squamous cell carcinoma (SCC) also positive for TTF-1 (1-4).
Napsin A is an aspartic proteinase expressed in type II pneumocytes and in adenocarcinomas of the lung (1). Napsin A has been found to be a sensitive and specific marker of lung ADC. Napsin A has been shown to positively stain 85-90% of cases of lung ADC, while negative staining has been observed in nearly all cases of lung SCC (1-6).
The antibody cocktail of TTF-1 + Napsin A has demonstrated a sensitivity of 91% (105/115) for lung ADC and 95% specificity (5/95) versus lung SCC (2). In cases where TTF-1 and Napsin A are both positive, specificity versus lung squamous cell carcinoma has been shown to be 100% (2).
1. Ueno T, Linder S, Steterger G. Aspartic proteinase napsin is a useful marker for
diagnosis of primary lung adenocarcinoma. Br J Cancer. 2003 Apr 22; 88(8):1229-33.
2. Tacha D, et al. A 6-antibody panel for the classification of lung adenocarcinoma
versus squamous cell carcinoma. Appl Immunohistochem Mol Morphol. 2012 May; 20
3. Mukhopadhyay S, Katzenstein AL. Subclassification of non-small cell lung
carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an
immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6. Am J Surg
Pathol. 2011 Jan; 35(1):15-25.
4. Turner BM, et al. Napsin A, a new marker for lung adenocarcinoma, is
complementary and more sensitive and specific than thyroid transcription factor 1 in
the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by
tissue microarray. Arch Pathol Lab Med. 2012 Feb; 136(2):163-71.
5. Hirano T, et al. Usefulness of TA02 (Napsin A) to distinguish primary lung
adenocarcinoma from metastatic lung adenocarcinoma. Lung Cancer. 2003 Aug; 41
6. Suzuki A, et al. Napsin A is useful to distinguish primary lung adenocarcinoma from
adenocarcinomas of other organs. Pathol Res Pract. 2005; 201(8-9):579-86.
7. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22,
Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove
8. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory
workers from occupationally Acquired Infections; Approved guideline-Third Edition
CLSI document M29-A3 Wayne, PA 2005