TTF-1 monoclonal comparison

Early studies used polyclonal antibodies. The monoclonal antibody SPT24 appears to have greater sensitivity, at the expense of loss of specificity, by comparison with the clone 8G7G3/1. Most published studies have used the latter clone. I am only aware of one paper reporting staining with each of the clones BGX-397A5 and 1-2.A5.97, none for another commercially available clone, SPM150.

Immunohistochemical expression

SPT24 shows more intense staining of pneumocytes than does 8G7G1/11 and stains airways cells more extensively:

  Reference 9 SPT24 8G7G3/1  
alveolar and bronchiolar cells more cells some cells
bronchi lobulares and segmetales some cells, mainly basal and submucosal glands negative
neuroendocrine cells positive negative
     

 

 

 

scoring

SPT24 (from Novocastra)

8G7G3/1 (from Dako)

BGX-397A

 

Pulmonary small cell carcinoma

7/84, 16/199  

7/84, 14/199  

 

Pulmonary  carcinoid

14/238

4/238

 

Pulmonary atypical carcinoid

5/54, 2/109  

2/54, 0/109  

 

Pulmonary typical carcinoid

5/114, 15/419  

1/114, 4/419  

 

Primary pulmonary adenocarcinoma

72/861, 12/174, 134/1858

56/861, 11/174, 121/1858

 

Pulmonary large cell carcinoma

6/124, 22/478

5/124, 17/478

 

Pulmonary large cell neuroendocrine carcinoma

10/139  

4/139  

 

Pulmonary squamous cell carcinoma

2/144, 14/978

1/144, 1/978

 

Pulmonary carcinoma unclassified

10/228

7/228

 

Squamous cell carcinoma of head and neck

0/388

0/388

 

Salivary gland

1/568

1/568

 

Gastric adenocarcinoma

1/124, 1/1108

0/124, 1/1108  

 

Primary colorectal carcinoma

4/901, 3/62, 1/174, 3/1208

0/901, 0/62, 0/174, 3/1208

 

Lung metastases from primary colorectal adenocarcinoma

4/411

0/411

 

Nodal metastasis from colorectal carcinoma

13

13

 

Liver metastasis from colorectal carcinoma

13

13

 

Lung metastases from renal carcinoma

0/61

0/61

 

Gastric carcinoid

0/69

0/69

 

Intestinal carcinoid

0/28, 0/5494

0/284, 0/549

 

Pancreatic carcinoid

0/269

0/269

 

non-pulmonary poorly differentiated neuroendocrine carcinoma

8/459

5/459

 

Pancreas adenocarcinoma

0/54, 0/1108

0/54, 0/1108

 

Breast adenocarcinoma

0/144, 0/21, 0/348

0/144, 0/21, 0/348

 

Bladder, invasive urothelial carcinoma

5/988

5/988

 

Prostatic adenocarcinoma

0/84, 2/1608

0/84, 2/1608

 

Ovarian serous carcinoma

1/64, 1/205, 6/365

1/64, 0/205, 2/365

1/205

Ovarian clear cell carcinoma

0/54, 2/205, 1/75

0/54, 0/205, 1/75

2/205

Ovarian endometrioid carcinoma

0/54, 2/205, 0/75

0/54, 1/205, 0/75

2/205

Ovarian mucinous carcinoma

1/205, 1/35

0/205, 0/35

1/205

Ovarian poorly differentiated carcinoma

0/205

0/205

0/205

Ovarian serous cystadenoma

0/45

0/45

0/45

Ovarian mucinous cystadenoma

1/35, 0/25

0/35, 0/25

1/35

Ovarian malignant mixed Mullerian tumour

1/25

0/25

 

Uterine serous carcinoma

4/185

1/185

 

Uterine endometrioid carcinoma

4/185

1/185

 

Uterine malignant mixed Mullerian tumour

9/115

0/115

 

Glioblastoma multiforme

14/286

0/286

 

Gliosarcoma

0/16

0/16

 

Overall rate of anomalous positivity (i.e. excluding pulmonary, thyroid and small cell tumours) 73/1211 (6.0%) 20/1211 (1.6%)  

a: using the automated Envision+ HRP detection and the Dako autostainer
b: using the automated Bond Max system from Vision Systems

 

Comparison of TTF-1 clones and staining machines for assorted gynaecological carcinomas selected for their positivity5:

 

8G7G3/1

SPT24

Vision system

9/18

17/18

Dako autostainer

2/18

9/11

 

 

Comparison of primary and metastatic neuroendocrine pulmonary tumours shows that metastases retain their rate of positivity irrespective of the TTF-1 clone used9:

 

8G7G3/1

SPT24

  primary metastatic primary metastatic
typical carcinoid 0/3 0/3 1/3 1/3
atypical carcinoid 0/1 0/1 0/1 0/1
large cell neuroendocrine carcinoma 3/8 4/8 6/8 6/8
small cell carcinoma 5/7 5/7 6/7 6/7
Total 8/19 9/19 13/19 13/19

Gynaecological tumours stained for TTF-2 and surfactant B were negative5

References

1 Comperat E, Zhang F, Perrotin C, et al. Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin. Mod Pathol 2005; 18:1371-6

2 Penman D, Downie I,Roberts F. Positive immunostaining for thyroid transcription factor-1 in primary and metastatic colonic adenocarcinoma: a note of caution. J Clin Pathol 2006; 59:663-4

3 Wong NA, Kamel H, Sheffield EA, et al. Positive immunostaining for thyroid transcription factor-1 in colorectal adenocarcinoma using the 8G7G3/1 monoclonal antibody. J Clin Pathol 2008; 61:1070-1

4 Nordic immunohistochemistry Quality Control web site: this data has not been published in a journal. [uing multissue blocks: cut-off value for positivity: 10 % unequivocally stained nuclei]

5 Zhang PJ, Gao HG, Pasha TL, et al. TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems. Int J Gynecol Pathol 2009; 28:10-8

6 Galloway M,Sim R. TTF-1 staining in glioblastoma multiforme. Virchows Arch 2007; 451:109-11

7 Harlamert HA, Mira J, Bejarano PA, et al. Thyroid transcription factor-1 and cytokeratins 7 and 20 in pulmonary and breast carcinoma. Acta Cytol 1998; 42:1382-8

8 Matoso A, Singh K, Jacob R, Greaves WO, Tavares R, Noble L, et al. Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol. 2010 Mar;18(2):142-9.

9 La Rosa S, Chiaravalli AM, Placidi C, Papanikolaou N, Cerati M, Capella C. TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies. Virchows Arch. 2010 Oct;457(4):497-507.

This page last revised 29.1.2011.

©SMUHT/PW Bishop