Top

Published in:

Open Access 01-12-2011 | Research

Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

Authors: Nobuhiko Nagata, Yasuhiko Kitasato, Kentaro Wakamatsu, Masaharu Kawabata, Kazuo Fukushima, Akira Kajiki, Yoshinari Kitahara, Kentaro Watanabe

Published in: Diagnostic Pathology | Issue 1/2011

Abstract

Background

It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP) and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs).

Objectives

This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs.

Methods

We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK), and epithelial membrane antigen (EMA) in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells.

Results

In patients with usual interstitial pneumonia (UIP), the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio) in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP), many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis.

Conclusions

The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative/hyperplastic alveolar epithelial cells) may predict a worse prognosis for patients with IIPs, especially patients with UIP. A prospective study is needed to confirm these results.

Available only for authorised users

Wells AU, Hansell DM, Rubens MB, Cullinan P, Black CM, du Bois RM: The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis. Am Rev Respir Dis. 1993, 148: 1076-1082.CrossRefPubMed

Schwarz DA, Helmers RA, Galvin JR, Van Fossen DS, Frees KL, Dayton CS, Burmeister LF, Hunninghake GW: Determinants of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1994, 149: 450-454.CrossRef

Erbes R, Schaberg T, Loddenkemper R: Lung function tests in patients with idiopathic pulmonary fibrosis: are they helpful for predicting outcome?. Chest. 1997, 111: 51-57. 10.1378/chest.111.1.51.CrossRefPubMed

Gay SE, Kazerooni EA, Toews GB, Lynch JP, Gross BH, Cascade PN, Spizarny DL, Flint A, Schork MA, Whyte RI, Popovich J, Hyzy R, Martinez FJ: Idiopathic pulmonary fibrosis; predicting response to therapy and survival. Am J Respir Crit Care Med. 1998, 157: 1063-1072.CrossRefPubMed

American Thoracic Society/European Respiratory Society: Idiopathic pulmonary fibrosis: diagnosis and treatment, international consensus statement. Am J Respir Crit Care Med. 2000, 161: 646-664.CrossRef

King TE, Schwarz MI, Brown K, Tooze JA, Colby TV, Waldron JA, Flint A, Thurlbeck W, Cherniack RM, Idiopathic pulmonary fibrosis: Relationship between histopathologic features and mortality. Am J Respir Crit Care Med. 2001, 164: 1025-1032.CrossRefPubMed

Rudd RM, Prescott RJ, Chalmers JC, Johnston ID: British Thoracic Society study on cryptogenic fibrosing alveolitis: response to treatment and survival. Thorax. 2007, 62: 62-66. 10.1136/thx.2005.045591.PubMedCentralCrossRefPubMed

McCormack FX, King TE, Voelker DR, Robinson PC, Mason RJ: Idiopathic pulmonary fibrosis. Abnormalities in the bronchoalveolar lavage content of surfactant protein A. Am Rev Respir Dis. 1991, 144: 160-166.CrossRefPubMed

McCormack FX, King TE, Bucher BL, Nielsen L, Mason RJ: Surfactant protein A predicts survival in idiopathic pulmonary fibsosis. Am J Respir Crit Care Med. 1995, 152: 751-759.CrossRefPubMed

10.

Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S: Serum surfactant protein A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000, 162: 1109-1114.CrossRefPubMed

11.

Greene KE, King TE, Kuroki Y, Bucher-Bartelson B, Hunninghake GW, Newman LS, Nagae H, Mason RJ: Serum surfactant protein-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J. 2002, 19: 439-446. 10.1183/09031936.02.00081102.CrossRefPubMed

12.

Kinder BW, Brown KK, McCormack FX, Ix J, Kervitsky A, Schwarz MI, King TE: Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. 2009, 135: 1557-1563. 10.1378/chest.08-2209.PubMedCentralCrossRefPubMed

13.

Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N: Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology. 2006, 164-168. 10.1111/j.1440-1843.2006.00834.x.

14.

Takahashi H, Shiratori M, Kanai A, Chiba H, Kuroki Y, Abe S: Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D. Respirology. 2006, S51-S54. 10.1111/j.1440-1843.2006.00809.x.

15.

Hinata N, Takemura T, Ikushima S, Yanagawa T, Ando T, Okada J, Oritsu M, Koike M: Phenotype of regenerative epithelium in idiopathic interstitial pneumonias. J Med Dent Sci. 2003, 50: 213-224.PubMed

16.

American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med. 2002, 165: 277-304.

17.

Aherne WA, Dunnill MS: Preparation of tissues: sampling. Edited by: Aherne WA, Dunnill MS. 1982, Morphometry. London: Edward Arnold Ltd, 19-32.

18.

Nicholson AG, Fulford LG, Colby TV, du Bois RM, Hansell DM, Wells AU: The relationship between individual histologic features and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002, 166: 173-177. 10.1164/rccm.2109039.CrossRefPubMed

19.

Noth I, Martinez FJ: Recent advances in idiopathic pulmonary fibrosis. Chest. 2007, 132: 637-650. 10.1378/chest.06-1927.CrossRefPubMed

20.

Harrod KS, Trapnell BC, Otake K, Korfhagen TR, Whitsett JA: SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection. Am J Physiol. 1999, 277: L580-L588.PubMed

21.

Hickling TP, Sim RB, Malhotra R: Induction of TNF- release from human buffy coat cells by Pseudomonas aeruginosa is reduced by lung surfactant protein A. FEBS Lett. 1998, 437: 65-69. 10.1016/S0014-5793(98)01200-9.CrossRefPubMed

22.

Quintero OA, Korfhagen TR, Wright JR: Surfactant protein A regulates surfactant phospholipid clearance after LPS-induced injury in vivo. Am J Physiol Lung Cell Mol Physiol. 2002, 283: L76-L85.CrossRefPubMed

23.

Honda Y, Tsunematsu K, Suzuki A, Akino T: Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases. Lung. 1988, 166: 293-301. 10.1007/BF02714060.CrossRefPubMed

24.

Hughes DA, Haslam PL: Changes in phosphatidylglycerol in bronchoalveolar lavage fluids from patients with cryptogenic fibrosing alveolitis. Chest. 1989, 95: 82-89. 10.1378/chest.95.1.82.CrossRefPubMed

25.

Robinson PC, Watters LC, King TE, Mason RJ: Idiopathic pulmonary fibrosis: abnormalities in bronchoalveolar lavage fluid phospholipids. Am Rev Respir Dis. 1988, 137: 585-591.CrossRefPubMed

26.

Low RB: Bronchoalveolar lavage lipids in idiopathic pulmonary fibrosis. Chest. 1989, 95: 3-5. 10.1378/chest.95.1.3.CrossRefPubMed

27.

Burkhardt A: Alveolitis and collapse in the pathogenesis of pulmonary fibrosis. Am Rev Respir Dis. 1989, 140: 513-524.CrossRefPubMed

Title: Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias
Authors: Nobuhiko Nagata
Yasuhiko Kitasato
Kentaro Wakamatsu
Masaharu Kawabata
Kazuo Fukushima
Akira Kajiki
Yoshinari Kitahara
Kentaro Watanabe
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-6-25

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

Abstract

Background

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2011

Follicular bronchiolitis and lymphocytic interstitial pneumonia in a Japanese man

Atypical burkitt's lymphoma transforming from follicular lymphoma

Challenges to diagnose metaplastic carcinoma of the breast through cytologic methods: an eight-case series

Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases

Lymphoepithelioma-like carcinoma of the vulva, an underrecognized entity? Case report with a single inguinal micrometastasis detected by sentinel node technique

ABCG2 is associated with HER-2 Expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma