Immunohistochemical evaluation of nuclear 5-hydroxymethylcytosine (5-hmC) accurately distinguishes malignant pleural mesothelioma from benign mesothelial proliferations.
Mod Pathol
; 32(3): 376-386, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30315275
ABSTRACT
Accurate distinction of benign mesothelial proliferations from malignant mesothelioma remains a diagnostic challenge. Sequential use of BAP1 immunohistochemistry and CDKN2A fluorescence in situ hybridization is specific for diagnosis of mesothelioma, but fluorescence in situ hybridization is both costly and time-consuming. Early data indicate that mesothelioma shows extensive loss of nuclear 5-hydroxymethylcytosine (5-hmC). We studied 49 cases of mesothelioma (17 epithelioid mesothelioma, 22 biphasic mesothelioma, and 10 sarcomatoid mesothelioma) and 23 benign mesothelial proliferations using a 5-hmC single immunohistochemical stain, CAM5.2/5-hmC double immunohistochemical stain, and BAP1 immunohistochemistry. Estimations of extent of 5-hmC loss were made using the 5-hmC single stain and CAM5.2/5-hmC double stain, and extent of nuclear 5-hmC loss was definitively quantitated in at least 1000 cells per case. Mean nuclear 5-hmC loss in mesothelioma (84%) was significantly greater than in benign mesothelial proliferations (4%) (p < 0.0001). Using 5-hmC loss in > 50% of tumor nuclei to define the diagnosis of mesothelioma, 5-hmC immunohistochemistry showed sensitivity of 92% and specificity of 100%. An immunopanel including 5-hmC and BAP1 immunohistochemistry achieved sensitivity of 98% and specificity of 100%. Extensive nuclear 5-hmC loss is sensitive and specific for mesothelioma in the differential diagnosis with benign mesothelial proliferations. In challenging mesothelial lesions, immunohistochemical studies showing either extensive 5-hmC loss or BAP1 loss indicate a diagnosis of mesothelioma, precluding the need for CDKN2A fluorescence in situ hybridization in a considerable number of cases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pleurales
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Biomarcadores de Tumor
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Desoxicitidina
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Tumor Fibroso Solitario Pleural
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Neoplasias Pulmonares
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Mesotelioma
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article