The Diagnostic Utility ofp16FISH and GLUT-1 Immunohistochemical Analysis in Mesothelial Proliferations

Abstract

Two promising ancillary tests used in the diagnosis of mesothelioma include GLUT-1 immunohistochemical analysis and fluorescence in situ hybridization (FISH) testing for the p16 deletion. This study compared the diagnostic usefulness of p16 FISH and GLUT-1 immunohistochemical analysis in the diagnosis of mesothelial proliferations in 158 cases with a diagnosis of benign (45.4%), atypical (10.4%), or malignant/mesothelioma (44.2%). Of the 70 benign cases, none had a deletion of p16 and 5 cases (7%) were positive for GLUT-1. Of the 68 mesotheliomas, 40 (59%) had a deletion of p16 (sensitivity, 59%; specificity, 100%) and 27 (40%) were positive for GLUT-1 (sensitivity, 40%; specificity, 93%). GLUT-1 showed lower sensitivity in pleural (56% vs 70%) and peritoneal (29% vs 51%) mesotheliomas (P = .004). Our results demonstrate that p16 FISH is a more sensitive and specific test than GLUT-1 immunohistochemical analysis and can be a more reliable ancillary tool to support the diagnosis of mesothelioma.

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: 2012 Update of the Consensus Statement from the International Mesothelioma Interest Group

“…Similar to histologic specimens (as discussed in other sections of this article), application of immunocytochemical and molecular techniques, either on smears or on cell blocks, enhances greatly the possibility to reach a correct diagnosis. 8,[14][15][16][17] Molecular techniques, such as fluorescence in situ hybridization (FISH) in demonstrat- 5 Acurio et al, 6 Shi et al, 8 Monaco et al, 20 and Attanoos et al…”

“…ing homozygous deletion of the p16 gene in about 70% of mesothelial proliferations, are particularly promising, as reported specificity is 100%. [18][19][20] However, emerging data indicate that subtyping of epithelioid mesothelioma according to morphologic features and nuclear grade 21 is important to predict survival, hence a cytologic diagnosis of ''malignant mesothelioma epithelioid type'' might not be sufficient in the future. Apart from diagnostic difficulties, the frequent practice of litigation in cases of mesotheliomas makes pathologists reluctant to diagnose mesothelioma without histologic confirmatory evidence.…”

“…The FISH technique for detection of 9p21 deletions has been shown to be a very powerful technique for confirming the diagnosis of malignant mesothelioma in effusion and formalin-fixed, paraffin-embedded tissue specimens ( Figure 19, A and B). 19,20,86,88,89 The diagnosis of atypical mesothelial proliferation is more common in cytologic specimens than in surgical specimens because the diagnosis of mesothelioma can be more challenging in cytologic specimens because of the inability to evaluate for tissue invasion and of the numerous cytomorphologic mimics of mesothelioma, including reactive mesothelial proliferations. In the diagnosis of MM in effusion cytology across all cytologic categories, studies showed an overall sensitivity of p16 FISH between 56% and 79% with a positive predictive value of 100%.…”

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

“…12 In fact, a variety of markers, such as desmin, epithelial membrane antigen, p53, IMP3, GLUT-1, CD146, and CD147, have been evaluated on both tissue and cytological samples, but none of them appeared to achieve sufficient diagnostic adequacy in the separation between malignant and benign mesothelial lesions. Using fluorescence in situ hybridization (FISH), the homozygous deletion of CDKN2A gene is found in 52-88% of mesotheliomas, but not in reactive mesothelial proliferations; 23,37-39 using a cut-off value of 10% positive mesothelial cells, p16 protein expression resulted to be closely related to CDKN2A status in some, 23,38 but not all, studies, 37 thus hampering its use as a reliable marker to distinguish mesothelioma from reactive mesothelial proliferations.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…Therefore, the absence of p16 gene deletion cannot entirely exclude the diagnosis of malignancy. 96 In summary, the role of IHC can be helpful to confirm a diagnosis of MM, and the precise IHC panel should be selected with a careful consideration of the differential diagnosis. However, caution should be made when interpreting immunostains, because of staining variability among different antibody clones and individual IHC laboratories.…”