Caveolin‐1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma

Amatya, Vishwa Jeet; Takeshima, Yukio; Kohno, Hidekazu; Kushitani, Kei; Yamada, Taketo; Morimoto, Chikao; Inai, Kei

doi:10.1111/j.1365-2559.2009.03322.x

Cited by 32 publications

(39 citation statements)

References 33 publications

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“…Napsin A is a recently available lung adenocarcinoma marker that, similar to TTF-1, has also been reported to be frequently expressed in these tumors (B60-90%). 51,53,[58][59][60] All four of the signet-ring cell adenocarcinomas of the lung that were stained for napsin A in the present study exhibited strong positivity for this marker. To my knowledge, this is the first study on napsin A expression in signet-ring cell adenocarcinomas of the lung.…”

Section: Markermentioning

confidence: 87%

“…In those instances in which this differential diagnosis arises, immunohistochemical studies for lungassociated markers, such as TTF-1 50 and napsin A, 51 can greatly facilitate this distinction as these markers have been reported to be frequently expressed in lung adenocarcinomas, but absent in mesotheliomas. [52][53][54] The percentage of TTF-1 expression reported in signet-ring cell lung Table 3 Immunohistochemical results…”

Section: Discussionmentioning

confidence: 99%

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Mesothelioma with signet-ring cell features: report of 23 cases

Ordóñez

2013

Modern Pathology

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Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signetring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features. Modern Pathology (2013) 26, 370-384; doi:10.1038/modpathol.2012.172; published online 5 October 2012Keywords: electron microscopy; immunohistochemistry; signet-ring cell carcinoma; signet-ring cell mesotheliomaThe finding of occasional vacuolated cells exhibiting signet-ring-like morphology is not rare in mesotheliomas; however, epithelioid mesotheliomas having a large number of such cells are relatively uncommon and have been subclassified as signet-ring cell mesotheliomas. 1 Signet-ring cell carcinomas can arise in a wide variety of organs, including lung, 2-6 stomach, 7,8 colon, 8-10 breast, 8,11,12 urinary bladder, 13-17 pancreas, 18 salivary glands, 19 and prostate. [20][21][22][23][24][25][26][27][28] The signet-ring configuration seen in adenocarcinomas has traditionally been associated with the accumulation of large amounts of intracytoplasmic mucin. It can also occur as a result of the formation of a true intracytoplasmic lumen with displacement of the nucleus toward the periphery of the cell, in which case, spe...

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Section: Markermentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Mesothelioma with signet-ring cell features: report of 23 cases

Ordóñez

2013

Modern Pathology

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“…Thus, EM-D were epithelioid mesothelioma showing papillotubular pattern, micropapillary pattern, and/or microcystic pattern and EM-LD showing solid nest, trabecular pattern, signet-ring cell-like appearance and/or single cell infiltration pattern. One representative tissue block was used for immunohistochemical confirmation of mesothelioma using positive and negative antibody panels mentioned in our previous publications (21)(22)(23)(24)(25). This study consisted of 81 cases of epithelioid mesothelioma (EM) (61%), 34 cases of sarcomatoid mesothelioma (SM) (25%) and 19 cases of biphasic mesothelioma (BM) (14%).…”

Section: Methodsmentioning

confidence: 99%

Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines

et al. 2011

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Abstract. Mesothelioma, a highly aggressive cancer with poor prognosis and refractory to currently available therapies show increasing trends of its incidence in Japan and other developing countries. Although surgery is a gold standard for patients with early mesothelioma, most patients with advanced disease are not suitable for surgical resection and have option of palliative chemotherapy alone. One of the new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonal antibody therapy is under development. CD26, a 110-kDa transmembrane glycoprotein with known dipeptidyl peptidase IV activity, plays a role in tumor development and its expression was reported in various human malignancies. This study determined the preliminary selection criteria for humanized monoclonal anti-CD26 antibody therapy. Eighty-one epithelioid (49 differentiated and 32 less differentiated), 34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell lines were immunohistochemically examined using 8 different commercially available anti-CD26 antibodies for membranous and cytoplasmic expression. The cytoplasmic expression of CD26 was observed in all histological types of mesothelioma, while the membranous expression of CD26 was found in 88% of differentiated and 69% of less differentiated epithelioid mesothelioma, and none of sarcomatoid mesothelioma with anti-CD26 antibodies with rabbit polyclonal anti-DPP4 antibody and similar results were also obtained with goat polyclonal anti-DPP4/CD26 antibody. These antibodies absorbed with soluble human CD26 proteins do not show CD26 expression in mesothelioma tissue, suggesting these two antibodies localize true CD26 protein. Seven mesothelioma cell lines, including sarcomatoid types, also showed membranous expression of CD26 in cellblock preparation.CD26 vector transfection to CD26-negative MSTO-211H cells showed membranous expression of CD26 by flow cytometry, but not in tumor developed in NOD/SCID mice with inoculation of CD26 vector transfected MSTO-211H cells. We found that both rabbit and goat polyclonal antibodies are suitable for immunohistochemical evaluation of membranous expression of CD26 in mesothelioma.

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“…It is frequently expressed in all histologic types of mesothelioma, in contrast to other commonly used mesothelioma markers such as keratin 5/6, Wilms tumor 1 (WT1) protein, and podoplanin, which are often expressed in epithelioid mesotheliomas but usually absent in sarcomatoid mesotheliomas. The percentage of calretinin expression reported in epithelioid mesotheliomas has ranged from about 55% to 100% of the cases [2,[4][5][6][7][8][9][10][11][12][13][14][15][16]. This broad range in the percentage of calretinin positivity has been attributed to the type of antibody used in some studies [6].…”

Section: Calretininmentioning

confidence: 99%