E‐cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma

Leers, Math P.G.; Aarts, M. M. J.; Theunissen, P. H. M. H.

doi:10.1046/j.1365-2559.1998.00349.x

Cited by 104 publications

(108 citation statements)

References 23 publications

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“…3,6,26,30 In the present investigation, all of the mesotheliomas exhibited diffuse strong positivity for calretinin, thus confirming the findings of previous studies. 8,16,18,22,25,26,31 A total of 12 (40%) of the squamous carcinomas in the current study exhibited calretinin positivity and even though the staining was focal in most instances, in three of the cases, it was strong and diffuse.…”

Section: Discussionmentioning

confidence: 66%

“…16,17 In 1996, Doglioni et al 16 reported strong calretinin expression in all 36 epithelioid mesotheliomas, but only focal staining was found in 28 (10%) of 294 adenocarcinomas of various origins and in 10 (18%) of 55 squamous carcinomas also of various origins. While many subsequent investigations have confirmed the usefulness of calretinin immunostaining in the differential diagnosis between mesotheliomas and lung adenocarcinomas, 8,[18][19][20][21][22][23][24][25][26][27][28][29] only a relatively few studies have been published on the expression of this marker in squamous carcinomas of the lung. 3,6,26,30 In the present investigation, all of the mesotheliomas exhibited diffuse strong positivity for calretinin, thus confirming the findings of previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…53 The percentage of Ber-EP4 reactivity reported in lung adenocarcinomas has ranged from 96 to 100%, 8,21,22 and from 0 to 35% 8,22,25,54,55 in epithelioid mesotheliomas. Only a few studies have been published on the reactivity of Ber-EP4 in squamous carcinomas of the lung and the percentage of positivity has ranged from 29 to 100% of the cases.…”

Section: Discussionmentioning

confidence: 99%

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The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis y ), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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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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Cytologic differential diagnosis among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma

Kitazume

Kitamura

Mukai

et al. 2000

Cancer

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BACKGROUND The differential diagnosis between reactive mesothelial cells (RMs), malignant mesotheliomas (MMs), and adenocarcinomas (ACs) is often difficult in cytologic specimens, and the utility of various immunohistochemical markers have been explored. Because recent immunohistologic studies have suggested that E‐cadherin (E‐cad) and calretinin (Cal) may be useful markers for epithelial and mesothelial differentiations, respectively, the authors investigated their utility in cytologic diagnosis. METHODS In this retrospective study, immunostaining was performed on smears retrieved from Papanicolaou‐stained slides of effusions using the labeled streptavidin‐biotin method. Sixteen cases of RM, 9 cases of MM, and 52 cases of AC from various sites, including 13 pulmonary primaries, were examined with primary antibodies against E‐cad and Cal. RESULTS The positive rates for E‐cad and Cal, respectively, were as follows: RM, 0/16 (0%) and 16/16 (100%); MM, 9/9 (100%) and 8/8 (100%); and AC, 45/52 (86.5%) and 0/51 (0%). The E‐cad expression by neoplastic cells was strongest in the intercellular junctions, and poorly differentiated neoplastic cells in the single cell form showed the weakest expression. CONCLUSIONS In contrast to the results of previous immunohistochemical studies, the current study indicates that MMs constantly express E‐cad, whereas RMs lack its expression in cytologic specimens, which would be useful in the differential diagnosis between the two. On the other hand, E‐cad expression is not reliable for distinguishing AC from MM. The Cal expression can be a very useful marker for the distinction between AC and the mesothelial lineage. The combined immunostaining for E‐cad and Cal has utility in differential diagnosis among RM, MM, and AC. Cancer (Cancer Cytopathol) 2000;90:55–60. © 2000 American Cancer Society.

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E‐cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma

Abstract: The combination of E-cadherin/calretinin appears to be a suitable panel for distinguishing metastatic carcinomas and mesotheliomas in pleural lesions. The additional value of other markers is limited.

Cited by 104 publications

References 23 publications

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

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

Cytologic differential diagnosis among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma

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