Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies

Abutaily, AS; Addis, B. J.; Roche, William R.

doi:10.1136/jcp.55.9.662

Cited by 118 publications

(122 citation statements)

References 32 publications

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“…The immunohistochemical detection for the nuclear expression of TTF-1 is considered as a useful marker in favor of lung or thyroid origin because of its high specificity (95-100%). [9][10][11][12] In the literature, TTF-1 expression in nuclei has been shown in rare cases of adenocarcinomas arising outside from lung or thyroid: one weakly positive case of metastatic ovarian carcinoma 13 and one focal positive case of endometrial carcinoma. 14 Recently, our group has shown one positive adenocarcinoma of colorectal origins, 8 whereas no such positivity was reported in literature ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

et al. 2005

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Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastra's antibody and 56 cases (65%) with Dako's. Significant discordance was observed (Po 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibody's clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas. Keywords: TTF-1; lung; carcinoma; metastasis; colorectal Thyroid transcription factor-1 (TTF-1) is a tissuespecific transcription factor expressed in the epithelial cells of thyroid and lung (type II pneumocytes and Clara cells). Carcinomas arising from lung and thyroid also show frequent TTF-1 expression. 1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma. 7 Two main commercial available clones of monoclonal antibodies have been raised against TTF-1 for immunohistochemical use, 8G7G1/1 and SPT24, their diagnostic value in determining the lung or thyroid origin of adenocarcinoma has not yet been compared. Most of the studies show the high specificity of TTF-1 detection and have been published used the 8G7G1/1 clone. We previously reported one case of lung metastasis of colorectal origin, which showed a focal nuclear staining with the anti-TTF-1 antibody (clone SPT24)...

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Section: Discussionmentioning

confidence: 99%

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

et al. 2005

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“…Calretinin is expressed in both the cytoplasm and nucleus. According to the literature, its expression in malignant mesothelioma varies, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] but most authors report frequent expression in epithelioid malignant mesothelioma, with only few studies reporting expression below 90%. Interestingly, calretinin expression has been described in a wide variety of cells, including steroid-producing cells of the testis and ovary, adipocytes, eccrine-glands, keratinizing thymic epithelial cells and numerous tumors, for example Merkel cell carcinoma, Leydig cell tumors of the testis, esthesioneuroblastoma, adenomas of the adrenal gland, small cell carcinoma of the lung and adenomatoid tumor.…”

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confidence: 99%

“…The few publications that have evaluated calretinin expression in the three most frequent types of malignant mesothelioma separately present data that diverge from 18 to 100% positivity in sarcomatoid malignant mesothelioma, and 8 to 100% in biphasic malignant mesothelioma. 5,7,15,[18][19][20]33 The D2-40 staining frequency is also controversial in sarcomatoid and biphasic malignant mesothelioma. Whereas Chu et al 23 reported staining in all types of malignant mesothelioma, Ordóñ ez 24 did not detect any D2-40 staining in either sarcomatoid malignant mesothelioma or sarcomatoid areas of biphasic malignant mesothelioma.…”

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D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

et al. 2007

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Anti-calretinin antibodies are useful to differentiate adenocarcinomas from malignant mesotheliomas of the lung. Therefore, calretinin expression is rarely reported for sarcomatoid mesotheliomas. Anti-podoplanin antibodies (eg D2-40) react with lymphatic endothelia, Kaposi's sarcoma, lymphangioma and mesotheliomas. For the interpretation of spindle cell lesions of the pleura, knowledge of calretinin and D2-40 expression frequencies in sarcomatoid mesothelioma is desirable. To systematically investigate the sensitivity of calretinin and D2-40 antibodies in epithelioid and sarcomatoid areas of malignant mesotheliomas, a tissue microarray with 341 malignant mesotheliomas, including 112 epithelioid, 46 sarcomatoid and 183 biphasic tumors was constructed. Epithelioid and sarcomatoid differentiated tumor areas were clearly separated within the tissue microarray. Expression of calretinin and D2-40 was separately studied in epithelioid and sarcomatoid areas by immunohistochemistry. Calretinin expression was found in 91% of epithelioid and 57% of sarcomatoid tumor areas. D2-40 immunostaining was present in 66% of the epithelioid and 30% of the sarcomatoid tumor areas. A combination of calretinin and D2-40 increased the sensitivity in epithelioid tumor areas to 0.96 and in sarcomatoid tumor areas to 0.66. These data indicate that a combination of calretinin and D2-40 will improve diagnostic accuracy for spindle cell lesions of the pleura, whereas almost all epithelioid mesotheliomas are identified by calretinin alone. Modern Pathology (2007) 20, 248-255.

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“…Most of these markers, such as BerEP4, CD15, the thyroid transcription factor (TTF-1) and carcinoembryonic antigen (CEA) stain adenocarcinomas whereas calretinin and CK5/6 are positive in both benign and malignant mesothelial cells. [3][4][5][6][7][8] An appropriate panel of antibodies is useful to differentiate between mesothelioma and adenocarcinoma. Among markers of adenocarcinomas whatever their origin (CEA, BerEP4, CD15), BerEP4 is the most sensitive (80%) but at the same time is the least specific.…”

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confidence: 99%

“…Furthermore, 22% of mesotheliomas are stained with anti-E-cadherin antibody. 3,16 MOC-31 immunostaining is also a useful marker of lung adenocarcinomas although positive immunostaining in a limited number of cells has been described in malignant mesotheliomas. 18 The mesothelioma markers group includes CK5/6 and calretinin.…”

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Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

et al. 2004

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The distinction between pleural malignant mesothelioma and pleural infiltration by adenocarcinomas has complex therapeutic and medicolegal implications. Although the panel of adenocarcinoma-associated antibodies and one or two mesothelioma markers is useful in this purpose, most of these antibodies are not totally specific. We determined the diagnostic value of MUC4 immunostaining in this issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR. MUC4 is a membrane-bound mucin that has been suggested to be implicated in malignant progression in humans and rats. The MUC4 gene is expressed in various normal epithelial tissues of endodermic origin and carcinomas. In the respiratory tract, MUC4 transcripts have been detected in normal respiratory epithelium and lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that could be useful in diagnostic practice in the distinction between malignant mesothelioma and adenocarcinoma.

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Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies

Cited by 118 publications

References 32 publications

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

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