Immunohistochemical marker panels for distinguishing between epithelioid mesothelioma and lung adenocarcinoma

The distinction between epithelioid mesothelioma and lung adenocarcinoma remains an important diagnostic challenge for surgical pathologists. The aim of the present study was to select a limited and appropriate panel of antibodies that can differentiate between epithelioid mesothelioma and lung adenocarcinoma. Specimens of 90 epithelioid mesotheliomas and 51 lung adenocarcinomas obtained from Japanese cases were examined using calretinin, WT1, AE1/AE3, CAM5.2, cytokeratin (CK) 5/6, vimentin, epithelial membrane antigen (EMA), thrombomodulin, CEA, CA19-9, and CA125. Ninety-six percent of epithelioid mesotheliomas were positive for calretinin; 99% for WT1; 100% for AE1/AE; 97% for CAM5.2; 70% for CK 5/6; 91% for vimentin; 96% for EMA; 71% for thrombomodulin; 77% for mesothelin; 7% for CEA; 17% for CA19-9; and 85% for CA125. In contrast, 33% of lung adenocarcinomas were positive for calretinin; 16% for WT1; 100% for AE1/AE3, CAM5.2, and EMA; 41% for CK 5/6; 47% for vimentin; 20% for thrombomodulin; 69% for mesothelin; 98% for CEA; 73% for CA19-9; and 80% for CA125. For distinguishing between epithelioid mesothelioma and lung adenocarcinoma, the combination of CEA, calretinin and each WT1 or thrombomodulin was suggested to be the best panel of immunohistochemical markers.     

Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.     

The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas

AIMS: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies. METHODS AND RESULTS: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin. CONCLUSION: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.     

间皮相关抗体在胸膜恶性间皮瘤和胸膜转移癌鉴别诊断中的作用

目的　探讨calretinin、CK5 / 6、mesothelialcell(MC)、CEA和vimentin在胸膜恶性间皮瘤及胸膜转移性肺腺癌中的表达及其在鉴别诊断中的作用。方法　用免疫组化EnVision二步法检测 13例胸膜恶性间皮瘤和 13例胸膜转移性肺腺癌中的calretinin、CK5 / 6、MC、CEA、vimentin的表达情况。结果　calretinin、CK5 / 6、CEA在恶性间皮瘤与胸膜转移性肺腺癌中表达差异有显著性 (P <0 0 5 )。MC、vimentin在恶性间皮瘤和胸膜转移性肺腺癌中表达差异无显著性 (P >0 0 5 )。结论　间皮相关抗体calretinin、CK5 / 6及癌抗体CEA对鉴别胸膜恶性间皮瘤及胸膜转移性肺腺癌有诊断价值。     

Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour

AIMS: To investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma. METHODS AND RESULTS: Immunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ssE12, epithelial membrane antigen, MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma-associated antigens (thrombomodulin, HBME-1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ssE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME-1 and OC 125 in a membranous distribution. p53 protein expression was not detected. CONCLUSIONS: The immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.     

The combination of CEA, EMA, and BerEp4 and hyaluronan analysis specifically identifies 79% of all histologically verified mesotheliomas causing an effusion

A previously tested antibody panel identified three criteria of major importance for distinguishing between mesothelioma and adenocarcinoma (ACA): carcinoembryonic antigen (CEA), BerEp4, and epithelial membrane antigen (EMA) accentuated at the cell membrane. An extended panel, consisting of CEA, BerEp4, EMA, vimentin, mesothelioma antibody (HBME-1), thrombomodulin, Ca125, and sialyl-Tn was applied to effusions from 86 ACAs and 21 mesotheliomas. The specificities and sensitivities of the previously identified reactivity patterns were tested on the new material and the effect of the added antibodies was evaluated. Further, hyaluronan analysis was added as a parameter.The previously selected criteria remained fully predictive for mesothelioma and ACA, respectively, also in the extended material (in all, 139 ACAs and 57 mesotheliomas). With the addition of the hyaluronan value, 79% of the cases was identified with 100% specificity. Among the new antibodies sialyl-Tn seemed the most promising because it specifically identified ACAs not expressing CEA.     

Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity.

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.     

HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma

AIMS: To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained. CONCLUSIONS: Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.     

Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma

The aim of this study was to examine the expression of three putative mesothelioma-binding antibodies, thrombomodulin, OV 632 and HBME-1 in 42 malignant mesotheliomas (27 pleural and 15 peritoneal) and 32 pulmonary adenocarcinomas. Evaluation of their use in differentiating between the mesotheliomas and pulmonary adenocarcinomas was assessed. Thrombomodulin was expressed by 22 of 42 (52%) mesotheliomas but was seen in eight of 12 pure epithelial-type mesotheliomas of the pleura and in all four papillary epithelial peritoneal mesotheliomas. For pure epithelial mesotheliomas thrombomodulin was 75% sensitive. Only two of 32 pulmonary adenocarcinomas were immunoreactive yielding a 94% specificity for thrombomodulin. In comparison, OV 632 and HBME-1 showed 67% and 62% antibody sensitivity, respectively, for malignant mesothelioma but this was accompanied by low specificity (OV 632, 37%; HBME-1, 28%). Both OV 632 and HBME-1 are considered unsuitable for use in differentiating between mesotheliomas and pulmonary adenocarcinomas. We advocate the use of thrombomodulin as a mesothelioma-binding antibody in the standard panel of antibodies used in the evaluation of malignant mesothelioma.     

Immunohistochemistry in the differential diagnosis of mesothelioma and adenocarcinoma. Evaluation of 5 new antibodies and 6 traditional antibodies

The aim of this study was to evaluate three recently marketed putative mesothelioma-binding antibodies, calretinin, HBME-1 and thrombomodulin, and two putative adenocarcinoma-binding antibodies, AUA1 and MOC31, on paraffin sections from 28 mesotheliomas and 30 adenocarcinomas. Moreover, the expression of ACE, BerEP4, CA125, CA19.9, LeuM1 and vimentin was assessed. Calretinin, HBME-1 and thrombomodulin, which showed a 100%, 89% and 43% sensitivity, and a 50%, 70% and 87% specificity for mesothelioma respectively, were less efficient than vimentin (100% specificity and 67% sensitivity) for the positive identification of mesothelioma. AUA1, BerEP4 and MOC31 were 100% sensitive to adenocarcinoma, with BerEP4 and MOC31 having the highest specificity (86% each). The immunophenotype "vimentin-positive, ACE-negative, CA19.9-negative" yielded 100% sensitivity and 97% specificity for diagnosis of mesothelioma. We advocate the use of the four-marker panel of ACE, CA19.9, MOC31 (or BerEP4) and vimentin for differentiating mesothelioma from adenocarcinoma.     

Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura

AIMS: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC-31 and HBME-1 and compared the results with others from the literature. METHODS AND RESULTS: A multi-antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC-31) and mesothelial cell (HBME-1). Positivity for MOC-31 and Ber-EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and specificity (86.3% both antibodies) for carcinoma. Positive staining for HBME-1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and specificity (91.3% and 60%, respectively) for mesothelioma. A two-marker antibody panel with HBME-1 and MOC-31 was the most efficient for the distinction between carcinoma and malignant pleural mesothelioma. Conclusion: A combination of MOC-31 (an anti- epithelial marker) and HBME-1 (an anti-mesothelial marker) has a diagnostic efficiency of 76.1% for the distinction between carcinoma and mesothelioma in pleura.     

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.     

Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura.

Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adenocarcinoma-associated antibodies. However, several "mesothelium-associated" antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers--thrombomodulin, cytokeratin 5/6, calretinin, and CD44H--to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.     

Lymphohistiocytoid Mesothelioma: A Clinical,Immunohistochemical and Ultrastructural Study of Four Cases and Literature Review

Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31–73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2–20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.     

Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review

Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31-73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2-20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.     

Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.