Validation of Tissue Microarrays for Immunohistochemical Profiling of Cancer Specimens Using the Example of Human Fibroblastic Tumors

Hoos, Axel; Urist, Marshall J.; Stojadinovic, Alexander; Mastorides, Stephen; Dudás, Mária; Leung, Denis H. Y.; Kuo, David; Brennan, Murray F.; Lewis, Jonathan J.; Cordon‐Cardo, Carlos

doi:10.1016/s0002-9440(10)64075-8

Cited by 349 publications

(296 citation statements)

References 10 publications

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“…Tissue microarrays were assembled using a Manual Tissue Arrayer I (Beecher Instruments, Sun Prairie, WI, USA) as described previously. 4,5 A representative area of each case was identified on the conventional sections, and at least three cylinders per tissue were arrayed using a punch biopsy (needles with a diameter of 0.6 mm).…”

Section: Thyroid Epithelial Neoplasmsmentioning

confidence: 99%

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

et al. 2008

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Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation. Compared with TTF-1, the other two markers have scarcely been investigated in surgical pathology. The goal of this study is to evaluate the expressions of these markers in thyroid tumors of the full spectrum of differentiation, with special emphasis on anaplastic carcinomas. A total of 94 cases of thyroid neoplasms were studied: 17 papillary carcinomas, 18 follicular adenomas, 16 follicular carcinomas, 7 poorly differentiated carcinomas, 28 anaplastic carcinomas, and 8 medullary carcinomas. Immunostains for these three markers were performed. The antibodies to Pax8 and TTF-2 were also applied on 147 lung carcinomas as well as a variety of normal tissues and malignant tumors. All three markers were seen in papillary carcinomas, follicular adenomas and carcinomas, and poorly differentiated carcinomas in a diffuse manner, whereas their expressions in medullary carcinomas were variable. Pax8 was expressed in 79% of anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of the lung. Pax8 was expressed in renal tubules, fallopian tubes, ovarian inclusion cysts, and lymphoid follicles as well as renal carcinoma, nephroblastoma, seminoma, and ovarian carcinoma, but not in normal tissue and carcinomas of the lung. Pax8 is a useful marker for the diagnosis of anaplastic carcinomas, particularly when the differential diagnosis includes pulmonary carcinoma. In differentiated thyroid neoplasms, no significant difference in expression was seen in all the three transcription factors.

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Section: Thyroid Epithelial Neoplasmsmentioning

confidence: 99%

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

et al. 2008

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“…Tissue microarrays have proven highly representative in comparison with traditional evaluation through methods on large tissue samples. [40][41][42][43][44][45][46][47][48][49][50][51] …”

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confidence: 99%

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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“…One concern may be whether a 0.6 mm core of tissue used for the microarray can represent the whole tissue section and some articles have already addressed this issue. [30][31][32] A recent study by Camp et al 32 showed that a two-fold redundancy per case can lead to more than 95% concordance between tissue microarrays 32 Indeed, we recently found that maspin expression in non-small cell lung cancers was very heterogeneous, and tissue microarrays well represented this heterogeneity. 33 Another benefit of using the tissue microarray is that it provides a large data matrix.…”

Section: Discussionmentioning

confidence: 91%

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data

et al. 2004

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The tissue organization of the salivary gland is complex, and a large number of salivary gland tumor entities with a broad morphologic spectrum are listed, creating tumor classification schema for the salivary glands that are difficult to understand. In the present study, we attempted to examine how the anatomical components of the salivary gland are associated with morphological subtypes of tumors. We selected a panel of 12 molecules, which labeled one or some of the components, with all of the markers covering every component of the salivary glands. Using tissue microarray, expression profiles of these molecules were examined in four representative spots from each of 88 salivary gland tumors. The resulting large data matrix was analyzed using principle component analysis (PCA). We considered the first three eigenvectors to be significant; as the eigenvalues were more than 1.0 and the cumulative proportion achieved was 67%. Comparison with expression patterns in normal tissue suggested that the three components represented myoepithelial differentiation, and luminal and basal cell phenotypes. Then, we compared the PCA results with individual morphologic subtypes. Individual subtypes were clustered among the three dimensions of the components. This implies that salivary gland tumors may be well characterized by using only three components.

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Validation of Tissue Microarrays for Immunohistochemical Profiling of Cancer Specimens Using the Example of Human Fibroblastic Tumors

Cited by 349 publications

References 10 publications

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

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

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data

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