Ber-EP4 staining in effusion cytology: A potential source of false positives.

The distinction between reactive mesothelium and carcinoma in serous effusions can be very difficult. Immunocytochemistry (ICC) is the most widely used tool to improve the diagnostic accuracy of body fluid cytology, with several ICC markers being proposed. Ber-EP4 antibody has shown high sensitivity and specificity rates for diagnosing metastatic carcinoma. In our department, we have detected Ber-EP4 positivity in mesothelium in some cytological specimens. We reviewed all articles on Ber-EP4 staining in effusion cytology, summarized current findings and analyzed the staining pattern of all cases expressing Ber-EP4. Some cases showing Ber-EP4 positivity in mesothelium have been reported, most of which showed only weak Ber-EP4 staining or staining of less than 50% of mesothelial cells. However, some cases may show strong positivity both in cytological and histological specimens. Clinicians and pathologists should be aware of this source of misdiagnosis, and ICC results in mesothelium should be always interpreted cautiously and correlated with clinical tests, other ICC markers and patient's previous history.

P16 as a marker of carcinoma in effusions and peritoneal washing.

BACKGROUND: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68. RESULTS: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%. CONCLUSION: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

Cholesterol pericarditis associated with rheumatoid arthritis: A rare case report.

BACKGROUND: Cholesterol pericarditis (CP) is a special type of pericarditis. It is characterized by chronic pericardial effusion with high cholesterol concentration and with or without the formation of crystals in pericardial effusion. METHODS: In this case report, we described a 74-year-old male with massive pericardial effusion. He presented with no symptoms. However, he had 8-year history of rheumatoid arthritis medicated with methotrexate, celecoxib, and prednisone, and 5-year history of hypertension medicated with amlodipine besylate. On admission, transthoracic echocardiography revealed a large pericardial effusion. RESULTS: We performed pericardiocentesis for this patient and a lot of cholesterol crystals were found in pericardial effusion under the microscope. A successful operation of thoracoscopic pericardiectomy was proceeded, and the diagnosis was confirmed by surgical pathology. The patient was well recovered and discharged on the tenth day after surgery. It could be predicted that pericardiectomy under video-assisted thoracoscope could be a promising therapy for CP. CONCLUSION: Rheumatoid arthritis may cause CP with no symptoms. Pericardiectomy could be a promising therapy for CP.

Differentiation between Transudate and Exudate in Pericardial Effusion has almost no Diagnostic Value in Contemporary Medicine.

BACKGROUND: The biochemical analysis of pericardial fluid for differentiating transudate from exudate is often ordered and interpreted according to the criteria extrapolated from pleural effusions. However, the validity of this discrimination when applied to pericardial effusion is under question. METHODS: Patients who underwent pericardiocentesis between January 2004 and February 2014 were identified. Among them, 216 had essential medical records available and constituted the study population. The parameters specifically analyzed were the following: lactate dehydrogenase, total protein and glucose concentrations in both pericardial fluid and serum; pericardial fluid/serum ratios of lactate dehydrogenase and total protein content; and pH and specific gravity of pericardial fluid. RESULTS: Eighty-one percent of pericardial effusions were classified as exudate according to Light's criteria. Both exudate and transudate fluid characteristics were possible for all etiological causes except for tuberculosis in which all were exudates. Although multiple cutoff points for all parameters were tested, significant overlap between different causes persisted (all having an area under the receiver operating characteristic curve of < 0.7). Thus, a reasonable accuracy to differentiate one cause from another could not be achieved. CONCLUSIONS: Although often ordered, the biochemical analysis of pericardial fluid has almost no diagnostic value to distinguish among causes of pericardial effusion in contemporary medicine.

Poor Penetration of Antibiotics Into Pericardium in Pericardial Tuberculosis.

Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardial fluid in TB pericarditis have never been measured before. We recruited two cohorts of patients with TB pericarditis, and left a pigtail catheter in-situ for serial drug concentration measurements over 24 h. Altogether, 704 drug concentrations were comodeled for pharmacokinetic analyses. The drug concentrations achieved in pericardial fluid were compared to the minimum inhibitory concentrations (MICs) of clinical Mycobacterium tuberculosis isolates. The total rifampicin concentration pericardial-to-serum ratios in 16 paired samples were 0.19 ± 0.33. The protein concentrations of the pericardial fluid in TB pericarditis were observed to be as high as in plasma. The non-protein bound rifampicin concentrations in pericardial fluid were 4-fold lower than rifampicin MICs in the pilot study, and the peak concentration was 0.125 versus 0.208 mg/L in the second (p = 0.001). The rifampicin clearance from pericardial fluid was 9.45 L/h versus 7.82 L/h in plasma (p = 0.002). Ethambutol peak concentrations had a pericardial-to-plasma ratio of 0.55 ± 0.22; free ethambutol peak concentrations were 2.30-lower than MICs (p < 0·001). The pericardial fluid pH was 7.34. The median pyrazinamide peak concentrations were 42.93 mg/L versus a median MIC of 800 mg/L at pH 7.34 (p < 0.0001). There was no significant difference between isoniazid pericardial fluid and plasma concentrations, and isoniazid peak concentrations were above MIC. This is the first study to measure anti-TB drug concentrations, pH and protein in the pericardial TB fluid. Pericardial concentrations of the key sterilizing drugs for TB were below MIC, which could contribute to poor outcomes. A new regimen that overcomes these limitations might need to be crafted.

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study.

BACKGROUND: Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP. METHODS: From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points. RESULTS: Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001). CONCLUSIONS: uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

BACKGROUND: The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. METHODS: Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. RESULTS: Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. CONCLUSIONS: GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration.

Endocan measurement for the postmortem diagnosis of sepsis.

The vascular endothelium has been shown to play a pivotal role in the pathophysiology of sepsis through the expression of surface proteins and secretion of soluble mediators. Endocan (endothelial cell-specific molecule-1), a 50-kDa dermatan sulfate proteoglycan, is expressed by endothelial cells in lung and kidney and can be detected at low levels in the serum of healthy subjects. Increased concentrations were described in patients with sepsis, severe sepsis and septic shock compared to healthy individuals, with serum concentrations related to the severity of illness. In the present study, we investigated endocan, procalcitonin and C-reactive protein in postmortem serum from femoral blood in a series of sepsis-related fatalities and control individuals who underwent medicolegal investigations. Endocan was also measured in pericardial fluid. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases with documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various noninfectious causes of death. Postmortem serum endocan concentrations were significantly higher in the sepsis group, with values ranging from 0.519 ng/ml to 6.756 ng/ml. In the control group, endocan levels were undetectable in eleven out of sixteen cases. The results of the data analysis revealed similar endocan concentrations in the pericardial fluid of both studied groups. Endocan can be considered a suitable biological parameter for the detection of sepsis-related deaths in forensic pathology routine.

Automated quantification of DNA aneuploidy by image cytometry as an adjunct for the cytologic diagnosis of malignant effusion.

DNA aneuploidy is a cancer biomarker, which may have a potential diagnostic value in body effusion specimen. DNA aneuploidy is determined by measuring the DNA content of tested cells and comparing them with diploid cells (2c). In order to assess the value of automated DNA image cytometry (DNA-ICM) in the cytologic diagnosis of effusion, we measured DNA ploidy using an automated DNA-ICM analysis system in 126 consecutive effusion specimens and followed the cases for histologic diagnosis. Half of each effusion specimen was used to prepare cytologic smears for conventional cytologic diagnosis, while the other half was used to prepare a monolayer slide stained by Feulgen stain for automated ICM. By using Youden index, we found that 4 cells exceeding 2.5c is the optimal cut off value for aneuploidy, which has a sensitivity of 88.3% and specificity of 100% for diagnosis of malignant effusion. We also found that the DNA aneuploidy thresholds used for other types of cytologic specimens cannot be used in the diagnosis of effusion specimens. Our study demonstrated that automated DNA image cytometry is a simple, practical and cost-effective method for adjunct diagnosis of malignant effusion.

Diagnostic value of interferon-gamma assay in tuberculosis pericardial effusions: study on a cohort of Iranian patients.

Tuberculosis pericarditis as a potentially fatal complication of tuberculosis requires effective diagnosis and treatment. We evaluated the efficacy of interferon-gamma (IFN-gamma) and adenosine deaminase (ADA) for diagnosing tuberculosis pericarditis in a cohort of Iranian patients presenting with pericarditis. We enrolled 38 patients with presentation of pericarditis. All patients underwent diagnostic and therapeutic pericardiostomy with drainage and biopsy. Adenosine deaminase and interferon-gamma levels were determined in pericardial fluid samples of all patients. Pericardial tissue samples were submitted for histopathologic and microbiologic studies. Polymerase chain reaction (PCR) was performed on all pericardial fluid samples to detect Mycobacterium tuberculosis. From 38 patients with pericarditis, 7 cases were diagnosed as having tuberculosis pericarditis (18.4%). Mean concentration of interferon-gamma in tuberculosis group was significantly higher compared to non-tuberculosis group (69257 pg/l [range: 26600-148000] vs. 329 pg/l [range: 0-2200], P<0.000). Receiver operating characteristic (ROC) curve showed a value of 14400 pg/l as the cutoff point with a sensitivity of 100% and specificity of 100% for diagnosing tuberculosis pericardial effusion. Adenosine deaminase was not found to be significantly higher in tuberculosis group in comparison with non-tuberculosis causes of pericardial effusion (35.7 [range: 9-69] vs. 36.03 [range: 8-420], P=0.28). In this study interferon-gamma showed to be a valuable diagnostic test for detection of tuberculosis pericarditis among a cohort of Iranian patients. We suggest using interferon-gamma to diagnose tuberculosis pericarditis to make diagnose in case of suspicion. While in this study, adenosine deaminase measurement did not prove to have the characteristics of an accurate diagnostic test for tuberculosis pericarditis.

Postmortem analyses of gaseous and volatile substances in pericardial fluid and bone marrow aspirate.

A previous study suggested the usefulness of pericardial fluid (PCF) and bone marrow aspirate (BMA) for the postmortem analysis of ethanol. The present study reviewed forensic autopsy cases (n = 2,983), which included 683 cases with the following positive toxicological findings, to reassess ethanol distribution and to investigate other gaseous and volatile substances in blood, PCF and BMA. Toxicological analyses detected ethanol (>10 mg/dL, n = 345), acetone (>0.01 mg/dL, n = 402), cyanide (n = 282), toluene (n = 47), liquefied petroleum gas (LPG, n = 1), cresol (n = 1), trichloroethylene (TCE, n = 1) and hydrogen sulfide (H2S, n = 5) in 683 cases. Ethanol and acetone levels showed good correlations among right heart/peripheral blood, PCF and BMA with a few exceptions. Inhaled cyanide in a fire fatality and H2S in suicidal inhalation were substantially lower in PCF than in blood and BMA; however, ingested cyanide showed a higher level in PCF. Distribution of inhaled toluene largely varied by case; however, BMA levels were about twice as high as blood levels in abusers (n = 7). Inhaled LPG and TCE were also higher in BMA than in blood, whereas ingested cresol showed similar distributions in blood and PCF. These observations suggest the usefulness of PCF and BMA as alternatives to blood for postmortem toxicological analysis. The inclusion of these materials in routine analysis may be also useful to investigate pharmacokinetics and toxicokinetics in the death process and the influence of postmortem redistribution/diffusion.

Diagnosis of malignant pericarditis: a single centre experience.

BACKGROUND: Malignancy is the most common cause of effusive pericarditis with a haemodynamically significant amount of pericardial fluid. Early diagnosis and management of malignant pericarditis may significantly improve outcomes. AIM: To evaluate retrospectively the rate and clinical presentation of malignant pericarditis among patients undergoing invasive treatment, with a view to identification of optimal diagnostic modalities to distinguish this group among other patients. METHODS: We studied 191 patients (100 men and 91 women, median age 57 years, range 19-88 years) with effusive pericarditis who underwent invasive treatment in the National Institute of Tuberculosis and Lung Diseases in Warsaw in 1982- -2008 due to a significant amount of pericardial fluid and/or echocardiographic evidence of cardiac tamponade. Pericardiocentesis was performed in 93 cases, pericardioscopy in 61 cases, and substernal pericardiotomy in 37 cases. Pericardial fluid was sent for examination in all patients, and a pericardial specimen was obtained in 96 patients. The patients were divided into 3 groups: Group 1 included patients with malignant pericarditis (malignant cells found in the cytological examination of the pericardial fluid and/or neoplastic infiltration in the histological examination of the pericardial specimen), Group 2 included patients with probable malignant pericarditis (pericardial fluid without malignant cells with histologically confirmed malignancy at some other location), and Group 3 included patients with non-malignant pericarditis (negative cytological examination of pericardial fluid and histological examination of the pericardial specimen, with no evidence of malignancy during hospitalization and one-year follow-up). RESULTS: Malignancy was found in 111 (58%) of 191 patients, including 66 (35%) patients with definite malignant pericarditis and 45 (23%) patients with probable malignant pericarditis. Lung cancer, including adenocarcinoma, was the most common type of malignancy, present in 44 (67%) patients. Non-malignant pericarditis was found in 80 (42%) patients. Among patients with the diagnosis of malignancy (Groups 1 and 2), a positive result of the cytological examination of the pericardial fluid was obtained in 52 cases (sensitivity of 46%). Among patients without malignancy, a negative result of the cytological examination of the pericardial fluid was obtained in all 80 cases (specificity of 100%). Malignant infiltration was found in 20 of 44 patients with the diagnosis of malignancy (sensitivity of 46%) and in none among 52 patients without malignancy (specificity of 100%). Compared to patients with non-malignant pericarditis, patients with malignant pericarditis significantly more commonly presented with tachycardia of >100 bpm in a resting electrocardiogram (ECG) (in 77% of patients with malignant pericarditis vs. 43% of patients with non-malignant pericarditis, p = 0.01), low QRS amplitude (52% vs. 34%, respectively, p = 0.03), electrical alternans (19% vs. 3%, respectively, p = 0.001), echocardiographic evidence of cardiac tamponade (67% vs. 34%, respectively, p = 0.0001), enlarged mediastinal lymph nodes by chest computed tomography (CT) (90% vs. 29%, respectively, p <0.00001), pericardial thickness >8 mm by chest CT (62% vs. 16%, respectively, p <0.0001), and bloody pericardial effusion (94% vs. 43%, respectively, p <0.0001). Levels of carcinoembryonic antigen (CEA) and cytokeratin fragment-19 (CYFRA 21-1) in the pericardial fluid were higher in patients with malignant pericarditis compared to patients with non-malignant pericarditis, with median values of 40.8 ng/mL vs. 0.9 ng/mL, p <0.0001, and 162.85 ng/mL vs. 13.35 ng/mL, p <0.0001, respectively. CONCLUSIONS: 1. Malignancy was found in 58% of patients undergoing invasive treatment due to large pericardial effusion. 2. Cytological examination of the pericardial fluid and histological examination of a pericardial specimen showed high specificity (100%) but low sensitivity (46%) in the diagnosis of malignant pericarditis. 3. The most important predictors of malignant pericarditis included tachycardia of >100 bpm as revealed by the physical examination and ECG, echocardiographic evidence of cardiac tamponade, presence of enlarged mediastinal lymph nodes (>1 cm) and thickened pericardium (>8 mm) by chest CT, bloody pericardial effusion, and elevated levels of CEA (>5 ng/mL) and CYFRA 21-1 (>50 ng/mL) in the pericardial fluid.

[Treatment strategy of cardiac rupture due to blunt trauma].

Cardiac trauma is common in blunt injuries of the chest. However, survival after a cardiac rupture is not common, and only a certain percentage of the patients reach the hospital alive. We report on 3 cases of successful treatment of cardiac rupture due to blunt trauma; one by emergency surgical repair, and the others, conservative medical treatment. Echocardiography and computed tomography demonstrated pericardial effusion in all cases, and emergency pericardial drainage was performed. Gas analyses of arterial blood and pericardial effusion were made simultaneously. When the oxygen saturation levels of the pericardial effusion were lower than those of the arterial blood, we suspected the cardiac injury to be right-sided. When they were almost at the same level, we suspected it to be left-sided. Simultaneous gas analysis of arterial blood and pericardial effusion is considered to be an easy and useful diagnostic method to decide not only treatment strategy, but also operative approach and procedure in patients suffering from cardiac tamponade following cardiac injuries.

Rapid diagnosis of tuberculous pericarditis by ELISPOT assay.

We describe a case in which the rapid diagnosis of tuberculous pericarditis was made using the Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay on pericardial effusion mononuclear cells (PEMCs). The analysis of MTB-specific T-cells in PEMCs by ELISPOT may be useful for rapid decision-making in anti-tuberculous treatment.

[Morphology of acute myocardial infarction at prenecrotic stage].

We studied morphological changes of myocardium and content of glucose, potassium, calcium, sodium in pericardial fluid in persons who died suddenly of myocardial infarction at its prenecrotic stage at prehospital phase. It was established that acute myocardial infarction at prenecrotic stage can run in 2 morphological forms - either with transmural or with subendo- or epicardial localization of ischemic process in left ventricular wall. Transmural injury is characterized by large volume of ischemic damage of the left ventricle, generalized spasm of arterial system of the heart, changes of cardiomyocytes with derangement of their energy metabolism and contractile capacity. In subendo- or epicardial localization foci of ischemic injury alternated with areas of normal blood supply. Similar character of disturbances of rheological properties of blood with thrombosis of microcirculatory bed and of number of markers of ventricular fibrillation between these two forms create preconditions for increase of the zone of necrosis in myocardium and cause high risk of development of rhythm disorders.

The roles of natriuretic peptides in pericardial fluid in patients with heart failure.

BACKGROUND: It is well known that the plasma concentrations of atrial and brain natriuretic peptides, as cardiac hormones, are elevated in heart failure. HYPOTHESIS: Pericardial fluid in patients with various heart diseases contains both natriuretic peptides that are released into the pericardial fluid. However, it is unknown whether these peptides reflect cardiac function in patients with various heart diseases, more than both the peptides in blood. METHODS: Plasma and pericardial fluid samples were obtained from 22 patients undergoing cardiac surgery for the measurement of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in plasma and pericardial fluid. RESULTS: The ANP levels in pericardial fluid were higher in patients with impaired left ventricular systolic function (ejection fraction<50% versus>or=50%; 77.0+/-4.9 versus 14.0+/-50.9, p=0.017), but not BNP.However, BNP levels in pericardial fluid were significantly higher in patients with left ventricle dilatation (left ventricular diastolic dimension54 mm; 130.3+/-68.9: 709.7+/-324.7, p=0.0168). Moreover, BNP levels in pericardial fluid were significantly higher in Grade III than Grade II and I (Grade I: echo-free space<5 mm, Grade II: 5-10 mm, Grade III: >10 mm). CONCLUSION: These results suggest that BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular diastolic dysfunction, and that increased BNP levels in pericardial fluid may have an important pathophysiologic role in heart failure as a cardiocyte-derived antifibrotic factor.

Utility of anti-L523S antibody in the diagnosis of benign and malignant serous effusions.

BACKGROUND: Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor mRNA-binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions. METHODS: Seventy-six cases with paraffin-embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6. RESULTS: Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma. CONCLUSIONS: Anti-L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining.