Diagnostic Value of Sialic Acid in Malignant Pleural Effusions* Oktay lmecik, M.D.;t and Faruk Ozer, M.D. In this study, we measured pleural 8uid and serum sialic acid levels in 70 consecutive patients hospitalized with pleural effusions and serum sialic acid concentrations in 20 healthy individuals chosen as control group. The cause of 26 pleural effusions was malignancy, and diseases other than malignant neoplasms were determined as the cause of 44 cases. Mean serum sialic acid levels in the patients with malignancies were higher than the levels in patients with nonmalignant diseases and the control group. Mean sialic acid level in the patients with nonmalignant diseases was increased compared with control group, hut this increase was not as high as that in the patients with malignancies. In the patients with malignant neoplasms, mean pleural
8uid sialic acid content was also higher than that found in other diseases. Sialic acid concentration of pleural 8uid was correlated with serum concentration. However, pleural8uid to serum sialic acid ratio in malignant diseases was greater than that in the others. The specificity and sensitivity of pleural 8uid sialic acid level in excess of 0.075 mglml in distinguishing malignant effusions were 68 percent and 77 percent, respectively. These values for pleural 8uid/serum sialic acid ratio with the cut-ofT level of 0. 7 were 55 percent and 65 percent. Our findings indicate that determination of sialic acid level in malignant pleural effusions has a diag(Chest 1992; 102:1819-22) nostic value.
.l ccumulation of fluid in the pleural space is one of
the most common diagnostic problems encountered by pulmonary specialists. Pleural effusion is frequently the primary manifestation of intrathoracic disease, but it could also be seen in some extrathoracic or systemic diseases. In patients with pleural effusion, a careful and detailed investigation of a sample of the fluid is required to diagnose the etiology. 1 To establish the correct diagnosis, the primary diagnostic step is the identification of the fluid, taken by pleural punction, as either a transudate or an exudate. It is important because such an identification may eliminate some of possible causes in the differential diagnosis. 2 In the exudates, an accurate diagnosis can be made if the cytologic, histologic, biochemical, or bacteriologic results are positive. Despite evaluation of pleural fluid results, sometimes more extensive diagnostic procedures may be needed. However, the cause often presents a difficult diagnostic challenge and remains obscure in 10 to 20 percent of all cases.2 ·3 Differentiation between malignant and nonmalignant effusions is especially important. Accurate diagnosis of malignant effusions is difficult and the presence of malignancy frequently could not be proved.4 Therefore, various biochemical parameters are investigated in the pleural fluid that may be helpful for diagnosis. 5 ·6 An increasing number of biochemical parameters, also called tumor markers, have been available. It was reported that some of these have diagnostic value.
Tumor markers were investigated in the serum earlier, but some authors suggested that may also be useful for diagnosis of malignant serous effusions. s- 12 One of these markers is sialic acid. In the serum samples of patients with certain carcinomas and malignant ascites, sialic acid concentrations have been found elevated. 13-20 Sialic acid, a family of acylated derivatives of neuraminic acid, is widely distributed in mammals. It is a component of cell surface constituents and is usually terminally located at the nonreducing end of carbonhydrate chains of glycoproteins and glycolipids. Sialic acid has been found in elevated concentrations in neoplastic cells derived from lung, breast, stomach, colon, ovary, prostate, and liver tumors. In these malignancies, sialoglycoprotein and sialoglycolipid concentrations are also elevated in the serum, because of shedding or secretion by tumor cells. Elevation of serum sialic acid as reflected by serum total N-acetyl neuraminic acid concentration are not specific for one type of cancer, as elevations have also been reported in patients with lymphoma and malignant melanoma. 14.21·23 We supposed that implants of malignant cells in the pleural space could produce effusion with elevated concentration of sialic acid. We measured sialic acid level in pleural effusions and serum samples of the patients with malignant and nonmalignant diseases to discriminate each other. We also investigated whether there is any relation between serum and pleural fluid sialic acid concentrations.
*From the Sel~uk University, Faculty of Medicine, Department of Chest Diseases, Konya, Turkey. tProfessor of Medicine. Manuscript received October 4; revision accepted April 6.
We studied 70 consecutive patients with pleural effusion and 20 healthy persons chosen as a control group, at the Chest Diseases Department of Sel~uk University Faculty of Medicine, in the years
1"1
MATERIALS AND METHODS
CHEST I 102 I 6 I DECEMBER, 1992
1819
Table 2-Sialic Acid LRvels (Mean±SD)
Table 1-Carues of Pleural EffusionB No. of Cases
Causes Malignant (n = 26) Lungeaneer Pleural mesothelioma Eosophageal neoplasia Mediastinal neoplasia Nonmalignant (n = 44) Tubereulosis Pneumonia Cardiac failure Pulmonary thromboembolism Cirrhosis Chronic renal failure Nonspecific pleuml effusion
Malignant diseases Nonmalignant diseases Control
19 5 1 1 22 6 7 2
5
1989 to 1990. Pleural effusion was malignant in 44 patients and nonmalignant in 26 patients. The diagnosis was based on histologic analysis in every case. The causes are listed in Table 1. A sample of pleural fluid and blood of every patient was taken at the time of admission to the hospital and before beginning any treatment. In the mntrol group, only blood samples were mllected. Blood was obtained by venous arm puncture into 5-ml glass specimen (Vacutainer) tube. allowed to clot at room temperature for 20 min, and was centrifuged at 3,000 rpm for 5 min. Serum was removed with a Pasteur pipette and stored at - 20"C until assayed. All pleural fluids were studied cytologically and stored at - 20"C after centrifugation until evaluated fi>r sialic acid. Pleural biopsy specimens were taken using the technique described by Cope. Sialic acid was measured with "thiobarbituric acid assay," \Varren's method."' Student's t test ";th p w .J
CDC
8uid sialic acid content was also higher than that found in other diseases. Sialic acid concentration of pleural 8uid was correlated with serum concentration. However, pleural8uid to serum sialic acid ratio in malignant diseases was greater than that in the others. The specificity and sensitivity of pleural 8uid sialic acid level in excess of 0.075 mglml in distinguishing malignant effusions were 68 percent and 77 percent, respectively. These values for pleural 8uid/serum sialic acid ratio with the cut-ofT level of 0. 7 were 55 percent and 65 percent. Our findings indicate that determination of sialic acid level in malignant pleural effusions has a diag(Chest 1992; 102:1819-22) nostic value.
.l ccumulation of fluid in the pleural space is one of
the most common diagnostic problems encountered by pulmonary specialists. Pleural effusion is frequently the primary manifestation of intrathoracic disease, but it could also be seen in some extrathoracic or systemic diseases. In patients with pleural effusion, a careful and detailed investigation of a sample of the fluid is required to diagnose the etiology. 1 To establish the correct diagnosis, the primary diagnostic step is the identification of the fluid, taken by pleural punction, as either a transudate or an exudate. It is important because such an identification may eliminate some of possible causes in the differential diagnosis. 2 In the exudates, an accurate diagnosis can be made if the cytologic, histologic, biochemical, or bacteriologic results are positive. Despite evaluation of pleural fluid results, sometimes more extensive diagnostic procedures may be needed. However, the cause often presents a difficult diagnostic challenge and remains obscure in 10 to 20 percent of all cases.2 ·3 Differentiation between malignant and nonmalignant effusions is especially important. Accurate diagnosis of malignant effusions is difficult and the presence of malignancy frequently could not be proved.4 Therefore, various biochemical parameters are investigated in the pleural fluid that may be helpful for diagnosis. 5 ·6 An increasing number of biochemical parameters, also called tumor markers, have been available. It was reported that some of these have diagnostic value.
Tumor markers were investigated in the serum earlier, but some authors suggested that may also be useful for diagnosis of malignant serous effusions. s- 12 One of these markers is sialic acid. In the serum samples of patients with certain carcinomas and malignant ascites, sialic acid concentrations have been found elevated. 13-20 Sialic acid, a family of acylated derivatives of neuraminic acid, is widely distributed in mammals. It is a component of cell surface constituents and is usually terminally located at the nonreducing end of carbonhydrate chains of glycoproteins and glycolipids. Sialic acid has been found in elevated concentrations in neoplastic cells derived from lung, breast, stomach, colon, ovary, prostate, and liver tumors. In these malignancies, sialoglycoprotein and sialoglycolipid concentrations are also elevated in the serum, because of shedding or secretion by tumor cells. Elevation of serum sialic acid as reflected by serum total N-acetyl neuraminic acid concentration are not specific for one type of cancer, as elevations have also been reported in patients with lymphoma and malignant melanoma. 14.21·23 We supposed that implants of malignant cells in the pleural space could produce effusion with elevated concentration of sialic acid. We measured sialic acid level in pleural effusions and serum samples of the patients with malignant and nonmalignant diseases to discriminate each other. We also investigated whether there is any relation between serum and pleural fluid sialic acid concentrations.
*From the Sel~uk University, Faculty of Medicine, Department of Chest Diseases, Konya, Turkey. tProfessor of Medicine. Manuscript received October 4; revision accepted April 6.
We studied 70 consecutive patients with pleural effusion and 20 healthy persons chosen as a control group, at the Chest Diseases Department of Sel~uk University Faculty of Medicine, in the years
1"1
MATERIALS AND METHODS
CHEST I 102 I 6 I DECEMBER, 1992
1819
Table 2-Sialic Acid LRvels (Mean±SD)
Table 1-Carues of Pleural EffusionB No. of Cases
Causes Malignant (n = 26) Lungeaneer Pleural mesothelioma Eosophageal neoplasia Mediastinal neoplasia Nonmalignant (n = 44) Tubereulosis Pneumonia Cardiac failure Pulmonary thromboembolism Cirrhosis Chronic renal failure Nonspecific pleuml effusion
Malignant diseases Nonmalignant diseases Control
19 5 1 1 22 6 7 2
5
1989 to 1990. Pleural effusion was malignant in 44 patients and nonmalignant in 26 patients. The diagnosis was based on histologic analysis in every case. The causes are listed in Table 1. A sample of pleural fluid and blood of every patient was taken at the time of admission to the hospital and before beginning any treatment. In the mntrol group, only blood samples were mllected. Blood was obtained by venous arm puncture into 5-ml glass specimen (Vacutainer) tube. allowed to clot at room temperature for 20 min, and was centrifuged at 3,000 rpm for 5 min. Serum was removed with a Pasteur pipette and stored at - 20"C until assayed. All pleural fluids were studied cytologically and stored at - 20"C after centrifugation until evaluated fi>r sialic acid. Pleural biopsy specimens were taken using the technique described by Cope. Sialic acid was measured with "thiobarbituric acid assay," \Varren's method."' Student's t test ";th p w .J
CDC
