lewis-x-antigen and Mesothelioma

Immunohistochemistry is frequently employed to aid the distinction between mesothelioma and pulmonary adenocarcinoma metastatic to the pleura, but there is uncertainty as to which antibodies are most useful. We analysed published data in order to establish sensitivity and specificity of antibodies used to distinguish between these tumours with a view to defining the most appropriate immunohistochemical panel to use when faced with this diagnostic problem.. A systematic analysis of the results of 88 published papers comparing immunohistochemical staining of a panel of antibodies in mesothelioma with epithelioid areas, and pulmonary adenocarcinoma metastatic to the pleura. Results for a total of 15 antibodies were analysed and expressed in terms of sensitivity and specificity. The most sensitive antibodies for identifying pulmonary adenocarcinoma were MOC-31 and BG8 (both 93%), whilst the most specific were monoclonal CEA (97%) and TTF-1 (100%). The most sensitive antibodies to identify epithelioid mesothelioma were CK5/6 (83%) and HBME-1 (85%). The most specific antibodies were CK5/6 (85%) and WT1 (96%).. No single antibody is able to differentiate reliably between these two tumours. The use of a small panel of antibodies with a high combined sensitivity and specificity is recommended.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Biomarkers, Tumor; Cadherins; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin; Vimentin

Although it is generally accepted that immunohistochemistry can assist in distinguishing between epithelial mesotheliomas and metastatic adenocarcinomas to the serosal membranes, a great deal of controversy exists regarding not only the practical value of some of the markers currently used, but also which should be included as part of the routine diagnostic panel. Until recently, these panels consisted primarily of antibodies that stained adenocarcinomas but not mesotheliomas. Over the last few years, however, markers that are commonly expressed in mesotheliomas but not in adenocarcinomas have been recognized. The focus of this review is on those markers for which there is an indication that they have a practical use in the diagnosis of mesothelioma. Special emphasis is placed on those which have been most recently recognized.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Cadherins; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; DNA-Binding Proteins; Humans; Hyaluronan Receptors; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Thrombomodulin; Transcription Factors; WT1 Proteins

Topics: Biomarkers, Tumor; Humans; Lewis X Antigen; Male; Mesothelioma; Microscopy, Electron; Testicular Neoplasms

Most reports on antibodies that claimed to separate mesothelioma from pulmonary adenocarcinoma originated from academic centers or specialized immunohistochemistry laboratories, but little is known about how such stains perform in general practice laboratories. The Canadian Immunohistochemistry Quality Control program circulates tissue array slides to laboratories across Canada; these are stained and then interpreted by the local laboratory and by a set of experienced reviewers. For Canadian Immunohistochemistry Quality Control run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A total of 736 results (cores) were interpretable. If 3 of 4 staining results concordant with the diagnosis was accepted as definitive, 166/192 (86.4%) mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly diagnosed. However, if 4 of 4 concordant markers were required, then 93/192 (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of 4 marker results were discordant with the diagnosis). We conclude that, in a study based on results from nonspecialized laboratories, the combination of CEA, CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate when separating pulmonary adenocarcinomas from mesotheliomas; however, single negative or incorrect results are common, therefore the panel is only useful diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.

Topics: Adenocarcinoma; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; False Positive Reactions; Fucosyltransferases; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Quality Assurance, Health Care; Reproducibility of Results; S100 Calcium Binding Protein G; Sensitivity and Specificity; Tissue Array Analysis

Immunohistochemistry with panels of antibodies is a standard procedure to distinguish between malignant mesothelioma and metastatic adenocarcinoma. Most studies assess only the sensitivity and specificity for single antibodies, even when the paper concludes by recommending an antibody panel. It was the aim of this study to use a novel statistical approach to identify a minimal panel of antibodies, which would make this distinction in the majority of cases.. Two hundred consecutive cases of pleural malignancy (173 pleural mesotheliomas of epithelial type and 27 cases of secondary adenocarcinoma) were investigated using a standard panel of 12 antibodies (CAM5.2, CK5/6, calretinin, HBME-1, thrombomodulin, WT-1, EMA, CEA, CD15, B72.3, BG8, and TTF-1). Regression and classification tree-based methods were applied to select the best combination of markers. The modelling procedures used employ successive, hierarchical predictions computed for individual cases to sort them into homogeneous classes.. Labelling for calretinin and lack of labelling for BG8 were sufficient for definite correlation with a diagnosis of malignant mesothelioma. CD15 provided further differentiating information in some cases.. A panel of three antibodies was sufficient in most cases to diagnose, or to exclude, epithelial mesothelioma. Calretinin exhibits the strongest correlative power of the antibodies tested.

Topics: Adenocarcinoma; Antibodies; Biomarkers, Tumor; Cadherins; Diagnosis, Differential; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Mesothelioma; Regression Analysis; Sensitivity and Specificity

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Calbindin 2; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Ovarian Neoplasms; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

To see the distribution of Calretinin, thrombomodulin, CK5/6 and HBME-1 markers in various subtypes of mesotheliomas and extend the published data on this topic. The positivity of adenocarcinoma specific markers (CEA and BerEP4) in malignant mesotheliomas have also been evaluated.. Various markers in 173 cases of malignant mesotheliomas received over a period of 8 years were evaluated by immunohistochemistry.. In majority of malignant mesotheliomas i.e., epithelioid and biphasic types, the positive staining patterns complement the gold standard histologic diagnosis. However, in a small minority mainly sarcomatoid variant, heavy reliance cannot be placed on these markers. CEA and BerEP4 are useful negative markers of mesotheliomas, although occasionally these are positive in clear cut mesotheliomas.. Specificity of various markers in malignant mesotheliomas should be assessed according to histologic subtypes. The existing generation of markers is not reliable in diagnosis of sarcomatoid mesotheliomas. Fortunately this forms only a small group of mesothelial malignancy. In common epithelioid and biphasic variants calretinin, thrombomodulin, CK5/6, HBME-1 are sensitive positive markers whereas CEA and BerEP4 are negative markers of malignant mesotheliomas.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Coloring Agents; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma, Synovial; Soft Tissue Neoplasms; Thrombomodulin

To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum.. Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.. Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; CA-125 Antigen; Calbindin 2; Carcinoembryonic Antigen; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Diagnosis, Differential; Epithelium; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratin-5; Keratins; Lewis X Antigen; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Predictive Value of Tests; S100 Calcium Binding Protein G; Thrombomodulin

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns o

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calbindin 2; Child; DNA-Binding Proteins; Female; Humans; Immunoenzyme Techniques; Lewis X Antigen; Male; Mesothelioma; Middle Aged; S100 Calcium Binding Protein G; Sarcoma, Synovial; Soft Tissue Neoplasms; Thrombomodulin; Transcription Factors; WT1 Proteins

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.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Mucin-1; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

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.

Topics: Adenocarcinoma; Antigens, Surface; ATP Binding Cassette Transporter, Subfamily B; Biomarkers; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Mesothelioma; Mucin-1; Neoplasm Metastasis; Peritoneal Neoplasms; Pleural Neoplasms; Receptor, Platelet-Derived Growth Factor beta; S100 Calcium Binding Protein G; Thrombomodulin; Tumor Suppressor Protein p53; Vimentin

Anti-CEA, anti-vimentin, CAM5.2, BerEp4, Leu-M1 and anti-EMA were applied to effusions from 36 mesotheliomas, 53 adenocarcinomas and 24 reactive mesothelial proliferations. Stepwise logistic regression analysis selected three criteria of major importance for distinguishing between adenocarcinoma and mesothelioma: BerEp4, CEA and EMA accentuated at the cell membrane (mEMA), these three being of similar diagnostic value. The pattern BerEp4-, CEA- and mEMA+ was fully predictive for mesothelioma (sensitivity 47%), whereas the opposite pattern was fully predictive for adenocarcinoma (sensitivity 80%). Only EMA seemed to distinguish between mesotheliosis and mesothelioma. Comparison of reactivity in cytological and histological material from the same mesotheliomas showed similar staining frequencies for CEA and CAM5.2, with some random variation for Leu-M1 and EMA, whereas vimentin and BerEp4 reactivity was more frequent in cytological specimens.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Lewis X Antigen; Logistic Models; Lung Neoplasms; Mesothelioma; Mucin-1; Neoplasm Proteins; Pleural Effusion, Malignant; Sensitivity and Specificity; Vimentin

To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung.. 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.. 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.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calcium-Binding Proteins; Calreticulin; Diagnosis, Differential; DNA-Binding Proteins; Evaluation Studies as Topic; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Ribonucleoproteins; Transcription Factors; WT1 Proteins

Localized malignant mesothelioma is an extremely rare form of presentation of malignant mesotheliomas. Only six cases have been reported. A 66-year-old male, former smoker, with occupational exposure to asbestos for 35 years, presented complaining of increasing fatigability, low-grade fever and anorexia for 4 weeks. The chest radiography showed a left lung mass. The computed tomography showed a 5-cm left posterior mass. The biopsy showed malignant cells. The patient underwent a surgical en bloc resection of the tumor. Pathology revealed a localized, poorly differentiated mesothelioma. Immunohistochemistry was positive for cytokeratin and vimentin while negative for carcinoembryonic antigen and Leu-M1. The final diagnosis was localized malignant mesothelioma. Aggressive resection of the tumor has shown to increase survival in previous reports, although the biological behavior of such tumors is still difficult to predict.

Topics: Aged; Anorexia; Asbestos; Biopsy; Carcinoembryonic Antigen; Fatigue; Fever; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Occupational Exposure; Pleural Neoplasms; Prognosis; Smoking; Survival Rate; Tomography, X-Ray Computed; Vimentin

We report a 50-year-old man with a history of malignant pleural mesothelioma diagnosed 1 year previously and treated with pneumonectomy and radiotherapy who presented with an erythematous eruption on the left chest wall. A skin biopsy showed a proliferation of malignant epithelioid cells lining irregular clefts in the dermis. Some groups of cells were observed filling vascular lumina. Immunohistochemically, the tumor cells expressed cytokeratins (with antibodies AE1/AE3, MNF 116, and CAM 5.2), and epithelial membrane antigen (EMA), and were negative with Ulex europaeus (UE) and for carcinoembryonic antigen (CEA), CD34, CD15 (with LeuM1 antibody), and factor VIII-related antigen (FVIIIra). The histologic features and immunohistochemical profile were comparable to those observed in the primary pleural mesothelioma. This is the first reported case in which malignant mesothelioma metastatic to the skin presented as "inflammatory carcinoma." Although a very uncommon presentation, mesothelioma should be considered in the differential diagnosis of erythematous eruptions on the chest.

Topics: Adenocarcinoma; Antigens, CD34; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Mesothelioma; Middle Aged; Mucin-1; Pleural Neoplasms; Skin Neoplasms; Thorax; von Willebrand Factor

Recently, we have recommended immunocytochemistry on serous effusions with the monoclonal antibodies Ber-EP4 and EMA to be used as a routine procedure. In this study, our earlier defined immunocytochemical profiles were tested in daily diagnostic work for a period and the profiles were applicated on the corresponding cell blocks from the effusions, too. It is concluded that routine use of the benign, malignant epithelial, and malignant mesothelial immunocytochemical profiles is valuable and superior to cytomorphology alone. Additionally, immunocytochemical staining of smears proved slightly more sensitive than immunohistochemistry performed on sections from the cell blocks.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Renal Cell; Diagnosis, Differential; Exudates and Transudates; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Paraffin Embedding; Predictive Value of Tests; Vaginal Smears

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesothelioma. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulo-papillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thrombomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms; Lewis X Antigen; Mesothelioma; Mucoproteins; Pleural Neoplasms; Thrombomodulin; Uromodulin

Topics: ABO Blood-Group System; Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Neoplasm; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Lewis X Antigen; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms

Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

Topics: Adenocarcinoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Cycle; Diagnosis, Differential; Humans; In Situ Hybridization; Lewis X Antigen; Lung; Lung Neoplasms; Mesothelioma; Receptors, Cell Surface; Receptors, Thrombin; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Tumor tissues obtained from 5 cases of malignant mesothelioma and from 5 cases of primary adenocarcinoma of the lung have been studied on staining with the sialyl SSEA-1 antibody by the PAP method. Results in all cases of a malignant mesothelioma (both Epithelioid and Sarcomatous pattern) were absolutely negative. All cases of lung cancer, however, were positive, though in differing degrees. In evaluating a malignant mesothelioma, many reports have indicated that the negativity of CEA staining is useful in achieving the differential diagnosis from lung cancer. The sensitivity of the staining by sialyl SSEA-1 was found to be far better than that of CEA in examining either malignant mesothelioma or lung cancer. Thus, we found that not only CEA but also sialyl SSEA-1 antigen staining was useful for the diagnosing of a malignant mesothelioma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Male; Mesothelioma; Staining and Labeling

Monoclonal antibodies made against gastrointestinal carcinoma antigen (GICA) and stage specific embryonic antigen (SSEA) were evaluated for their ability to distinguish normal mesothelial cells present in pleural and peritoneal fluids from adenocarcinoma cells in tissue and cytology specimens. The presence of GICA was documented in a high percentage of adenocarcinomas from the gastrointestinal tract (75/98) and in 52% of pulmonary (15/29) and 29% of ovarian (6/21) adenocarcinomas. GICA was found infrequently in breast carcinoma (1/18) and not in mesotheliomas (0/16). A similar pattern of GICA expression was seen in malignant effusions from adenocarcinomas (18/47) and mesotheliomas (0/6). SSEA was found in a high percentage of adenocarcinomas derived from the gastrointestinal tract (47/56) and the lung (26/29). SSEA was detected in breast carcinoma (8/15) more often than GICA. SSEA was detected rarely in mesotheliomas (1/16). Reactivities for epithelial membrane antigen, keratin, carcinoembryonic antigen, GICA and SSEA in adenocarcinoma and mesotheliomas were compared.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Breast Neoplasms; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms