Tuberc Respir Dis.  2014 Jan;76(1):15-22.

The Significance of Caspase-Cleaved Cytokeratin 18 in Pleural Effusion

• Lee KS
• Chung JY
• Jung YJ
• Chung WY
• Park JH
• Sheen SS
• Lee KB
• Park KJ

Abstract

BACKGROUND
Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion.
METHODS
A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30.
RESULTS
The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1+/-1,467.3 U/mL) than in patients with lung cancer (956.5+/-618.5 U/mL), parapneumonic effusion (689.9+/-413.6 U/mL), and transudates (273.6+/-144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues.
CONCLUSION
Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.

Keyword

Pleural Effusion; Apoptosis; Tuberculosis, Pleural; Cytoskeleton; Epithelioid Cells

MeSH Terms

Apoptosis
Biomarkers
Cytoskeleton
Enzyme-Linked Immunosorbent Assay
Epithelial Cells
Epithelioid Cells
Exudates and Transudates
Granuloma
Humans
Immunohistochemistry
Keratin-18*
Keratins*
Lung Neoplasms
Pleural Effusion*
ROC Curve
Tuberculosis
Tuberculosis, Pleural
Keratin-18
Keratins

Figure

• 

  Figure 1 Comparison of M30 levels in serum (A) and pleural fluid (B) among patients with malignant pleural effusion, parapneumonic effusion, tuberculous pleural effusion, and transudate. The horizontal bar represents the median values. *p<0.01 compared to transudate group, **p<0.01 compared to all other groups.

• 

  Figure 2 Correlation of level of M30 in pleural fluids with total cell count (A), lymphocyte count (B), total protein level (C), and adenosine deaminase level (D).

• 

  Figure 3 Receiver operating characteristic analysis of M30 and adenosine deaminase (ADA) levels in pleural fluid for differentiating tuberculous pleural effusion from all other effusions.

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  Figure 4 Immunohistochemical staining for M30 in pleural tissues of lung cancer and parapneumonic effusion. M30 is mainly expressed in cancer cells of squamous cell carcinoma (A), adenocarcinoma (B), and small cell carcinoma (C). (D) Parapneumonic effusion showed weak expression. The inset in panel A shows the perinuclear staining pattern (A-D, ×200).

• 

  Figure 5 Immunohistochemical staining for M30 in pleural tissue of tuberculous pleural effusion. M30 is mainly expressed in the epithelioid cells (×200).

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