Representative duplicate cores of 0.6?mm were utilized for tissue microarray construction after careful selection based on H&E and CD30-stained Amezinium methylsulfate sections, as previously described [12, 13]. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 main cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK?+?ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that this absence of staining around the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to Amezinium methylsulfate the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol. Keywords: ALK, Anaplastic large cell lymphoma, Immunohistochemistry Introduction The oncogene plays a critical role in the pathogenesis of a wide variety of both hematolymphoid and non-hematolymphoid neoplasms. Many aberrations involving the oncogene are rearrangements that lead to the fusion of the catalytic tyrosine kinase domain name of to a partner that leads to inappropriate expression of the ALK protein, which is normally only expressed in a subpopulation of cells in the developing embryonic and neonatal brain [1]. The detection of rearrangements or expression of the protein has become the standard of care to diagnose a variety of tumors and to predict responsiveness to therapies that target Amezinium methylsulfate the ALK tyrosine kinase. Among anaplastic large cell lymphomas (ALCLs), the separation of ALK-positive from ALK-negative tumors is required because the end result of ALK-positive ALCL is generally superior to that of most ALK-negative ALCL subtypes [2C5]. ALK expression is also useful to distinguish main cutaneous ALCL, which is usually ALK-negative, from cutaneous involvement by a systemic ALK-positive ALCL. Therefore, a sensitive immunodiagnostic assay to detect ALK protein is usually of high clinical relevance. In order to detect diagnostically and therapeutically relevant ALK abnormalities, many centers, including ours, perform immunohistochemical and/or cytogenetic studies. Detection of expression by immunohistochemistry has been shown to be a reliable surrogate for rearrangements and thus represents a useful tool in the routine diagnostic classification of tumors. Numerous antibodies are commercially available, and several of them have Mouse monoclonal antibody to NPM1. This gene encodes a phosphoprotein which moves between the nucleus and the cytoplasm. Thegene product is thought to be involved in several processes including regulation of the ARF/p53pathway. A number of genes are fusion partners have been characterized, in particular theanaplastic lymphoma kinase gene on chromosome 2. Mutations in this gene are associated withacute myeloid leukemia. More than a dozen pseudogenes of this gene have been identified.Alternative splicing results in multiple transcript variants been compared in prior studies, with some variability in sensitivity and specificity [6C11]. Our clinical immunodiagnostic lab has used an immunohistochemical stain protocol based on the ALK01 clone to detect ALK expression in hematolymphoid tumors. Based on a conversation with laboratory directors at other institutions, the ALK01 clone has been a commonly used antibody for the detection of ALK expression in ALK-positive anaplastic large-cell lymphoma. Though the ALK01 clone is the predominant clone utilized for the detection of ALK expression in ALK-positive anaplastic large cell lymphoma, it is well documented that it is less sensitive than other protocols for the detection of ALK expression in non-hematolymphoid tumors such as non-small cell lung malignancy [7]. This has led some laboratories to validate and maintain a separate ALK stain using a high-sensitivity ALK protocol for use in solid tumors in addition to ALK01-based protocols for ALK-positive anaplastic large cell lymphoma. In our laboratory, in addition to the ALK01 protocol, we validated a high-sensitivity ALK assay using the 5A4 antibody to detect ALK expression in non-hematolymphoid neoplasms. This high-sensitivity ALK assay was validated and has thus far exceeded all College of American Pathologists high-sensitivity ALK assay proficiency testing surveys between 2019 and 2022. In this study, we set out to determine if the 5A4-based protocol used in our laboratory is non-inferior to the ALK01-based protocol for the diagnosis of ALK-positive ALCL. The results of this study demonstrate that our 5A4-based protocol is usually non-inferior to the ALK01-based protocol, thus providing the rationale for the.
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