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Thyroid transcription factor-1 (TTF-1) is a member of the NKX2 family of homeodomain transcription factors. Studies have shown that TTF-1 is expressed in epithelial cells of the thyroid gland and lung. TTF-1 has been shown to be a sensitive (62-80%) and specific marker (89-95%) in the majority of primary lung
adenocarcinomas (ADC) (1-7). When combined in a cocktail with a rabbit polyclonal p40, TTF-1 was reported to demonstrate 77% sensitivity for lung ADC, and 100% specificity vs. lung squamous cell carcinoma (SCC) (7).
p40 has been shown to be selectively expressed in lung SCC, offering the potential for increased specificity compared to p63 (8-9). Mouse monoclonal p40 [BC28] recognizes an epitope unique to p40 and has been shown to be sensitive, staining 93% (99/107) of cases of lung SCC and specific, staining 0.8% (1/121) of cases of lung ADC (10).
Chimeric rabbit monoclonal rabbit p40 [BC28/cRM] was designed to replicate the sensitivity and specificity of mouse monoclonal p40 [BC28] as a rabbit antibody that would be suitable for a double-stain procedure. The variable regions of p40 [BC28], which define the binding sensitivity and specificity of the antibody, were cloned and fused with the constant regions of rabbit IgG to provide the chimeric rabbit monoclonal.
p40 [BC28/cRM]. In a side-by-side study on the same tissues, mouse monoclonal p40 [BC28] and chimeric rabbit monoclonal p40 [BC28/cRM] exhibited identical sensitivity (8/10) for lung SCC and specificity versus lung ADC (0/12). PATENT PENDING.
Mouse Monoclonal, Rabbit Monoclonal
Amino Acids 5-17 of p40, TTF-1
Lung adenocarcinoma (TTF-1), Lung SCC (p40)
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versus squamous cell carcinoma. Appl Immunohistochem Mol Morphol. 2012 May;20
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An Evaluation of Sensitivity and Specificity and Correlation of Tumor Grade for Lung
Adenocarcinoma versus Squamous Cell Carcinoma. Mod Pathol. 2011 Feb; 24
3. Tacha D, Zhou D, Henshall-Powell RL. Distinguishing Adenocarcinoma from
Squamous Cell Carcinoma in the Lung Using Multiplex IHC Stains: p63 + CK5 and
TTF-1 + Napsin A. Mod Pathol. 2010 Feb; 23(Supplement 1s):414A.
4. Mukhopadhyay S, Katzenstein AL. Subclassification of non-small cell lung
carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an
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adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg
Pathol. 2010 Dec; 34(12):1805-11.
6. Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1
expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and
malignant mesothelioma. Hum Pathol. 2010 Jan; 41(1):20-5.
7. Brown AF, et al. Tissue-preserving antibody cocktails to differentiate primary
squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of lung. Arch
Pathol Lab Med. 2013 Sep;137(9):1274-81.
8. Bishop JA, et al. p40 is superior to p63 for the diagnosis of pulmonary squamous
cell carcinoma. Mod Pathol. 2012 Mar; 25(3):405-15.
9. Hibi K, et al. AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl
Acad Sci U S A. 2000 May 9; 97(10):5462-7.
10. Tacha D, Bremer R, Haas T, Qi W. An immunohistochemical analysis of a newly
developed, mouse monoclonal p40 (BC28) antibody in lung, bladder, skin, breast,
prostate, and head and neck cancers. Arch Pathol Lab Med. 2014 Oct;138(10):1358-64.
11. Pelosi G, et al. p40 and thyroid transcription factor-1 immunoreactivity on small
biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparingmaterial
approach. J Thorac Oncol. 2012 Feb; 7(2):281-90.
12. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22,
Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove
13. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory
Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition
CLSI document M29-A4 Wayne, PA 2014.