Surfactant proteins

Pulmonary surfactant contains a number of proteins including the 10 kD Clara cell protein and surfactant proteins A, B, C and D. As markers of primary pulmonary adenocarcinoma, they are inferior to TTF-1.

Surfactant apoprotein A appears to be a major constituent of giant lamellar bodies.

PE-10 is a monoclonal antibody against components of human surfactant proteins4. Staining may be a combination of cytoplasmic and nuclear inclusions12. It is said to have high specificity for adenocarcinoma of the lung when compared to the results obtained with polyclonal antibodies5.

Immunoreactivity

 

PE-10

Sp-A

Sp-B

TTF-1

primary lung tumours

adenocarcinoma

6/164, 18/7512, 13/2113

25/461

29/461, 52%6, 119/20911

35/461, 158/20911

squamous cell carcinoma

0/84, 0/512

2/101

0/101, 0/10111

0/101, 0/10111

adenosquamous carcinoma

 

1/11

1/11

1/11

small cell carcinoma

0/54, 0/112

 

 

 

large cell carcinoma

0/64, 0/812

 

12/6111

16/6111

pleomorphic carcinoma

 

19/552

 

 

Malignant mesothelioma

0/913

 

0/9511

0/9511

primary breast carcinoma

 

4/511

0/511

0/511

breast carcinoma metastatic to lung

1/64

6/131

6/131

0/131

carcinoma metastatic to lung

1/144

 

 

 
         

Papilllary and bronchoalveolar carcinoma of the lung may show apparent nuclear positivity, which is attributable to the presence of nuclear inclusions containing material with the antigenicity of surfactant A7. Such nuclear inclusions have been shown to co-express TTF-17.

It appears that breast tumour cells metastatic to the lung incorporate pulmonary surfactant proteins, which are therefore of little value if differentiating metastatic breast carcinoma from primary pulmonary adenocarcinoma1.

The pattern of staining for surfactant A is different in primary pulmonary adenocarcinoma and mesothelioma, but there are many more informative antibodies.

 

adenocarcinoma

mesothelioma

Surfactant A

35/35 (9 membranous, 26 cytoplasmic)3

40/41 (33 membranous, 7 cytoplasmic)3

Surfactant B

6/2410

2/1310

Diagnostic utility

Surfactant is exclusively produced by the lung such that one might expect it to provide be a good lung-specific marker. However, this does not appear to be the case. Although displaying some specificity for lung and lung tumors, antibodies to surfactants used for immunohistochemistry lack sensitivity and specificity. According to some authors, only 63% of primary lung carcinomas stain with surfactant protein A and B while 46% of metastatic carcinomas, including primary breast cancers, stain with surfactant A and B antibodies9.

References

1 Bejarano, P. A., Baughman, R. P., Biddinger, P. W. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol 1996;9:445-452.

2 Rossi, G., Cavazza, A., Sturm, N., Migaldi, M., Facciolongo, N., Longo, L., Maiorana, A. and Brambilla, E. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol 2003;27:311-24.

3 Abutaily, A.S., Addis, B.J. and Roche, W.R. Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 2002;55:662-8.

4 Chhieng DC, Cangiarella JF, Zakowski MF, et al. Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens. Cancer 2001; 93:330-6 FULL TEXT

5 Goldmann T, Galle J, Wiedorn KH, et al. Diagnostic value of immunohistochemically detected surfactant--apoprotein-A in malignant tumors located in the lungs: report of two cases. Ann Diagn Pathol 2001; 5:84-90

6 Zou SM, Lin DM, Lu N, et al. [Use of thyroid transcription factor-1, surfacfant protein-B, cytokeratin 7 and cytokeratin 20 in discrimination between primary and metastatic adenocarcinoma of lung]. Zhonghua Yi Xue Za Zhi 2003; 83:1350-2

7 Lu SH, Ohtsuki Y, Nonami Y, et al. Ultrastructural study of nuclear inclusions immunohistochemically positive for surfactant protein A in pulmonary adenocarcinoma with special reference to their morphogenesis. Med Mol Morphol 2006; 39:214-20

9 Jagirdar J. Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008; 132:384-96 FULL TEXT

10 Bakir K, Kocer NE, Deniz H, et al. TTF-1 and surfactant-B as co-adjuvants in the diagnosis of lung adenocarcinoma and pleural mesothelioma. Ann Diagn Pathol 2004; 8:337-41

11 Khoor A, Whitsett JA, Stahlman MT, et al. Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. Hum Pathol 1999; 30:695-700.

12 Mizutani Y, Nakajima T, Morinaga S, et al. Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas. Cancer 1988; 61:532-7

13 Noguchi M, Nakajima T, Hirohashi S, et al. Immunohistochemical distinction of malignant mesothelioma from pulmonary adenocarcinoma with anti-surfactant apoprotein, anti-Lewisa, and anti-Tn antibodies. Hum Pathol 1989; 20:53-7

Nicholson AG, McCormick CJ, Shimosato Y, et al. The value of PE-10, a monoclonal antibody against pulmonary surfactant, in distinguishing primary and metastatic lung tumours. Histopathology 1995; 27:57-60

Di Loreto C, Di Lauro V, Puglisi F, et al. Immunocytochemical expression of tissue specific transcription factor-1 in lung carcinoma. J Clin Pathol 1997; 50:30-2

*** to be done ***

 

This page last revised 21.11.2008.

©SMUHT/PW Bishop