Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue

Abstract

Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the p16 status of effusion smears and that of the underlying MPM tissues has not been investigated. We used p16‐specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were p16 HD‐positive. Conversely, MPM cells in the remaining six tumors (30%) were p16 HD‐negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed p16 deletion. Moreover, the extent to which p16 was deleted in smears highly correlated with the extent of p16 deletion in tissues. The p16 deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of p16 deletion in cytologic smear samples does not preclude MPM.

BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests

“…Dual‐color probes were used for the FISH studies, which were performed on the formalin‐fixed, paraffin‐embedded, 4‐μm‐thick tissue histologic sections. The probes were a Spectrum Green‐labeled chromosome 9 centromeric probe and a Spectrum Orange‐labeled, locus‐specific p16 probe (Vysis LSI p16/CEP 9 probe; Abbott Japan, Tokyo, Japan) …”

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

“…Hemizygous or homozygous deletion of p16 was not seen in fibrous pleurisy (FP), but was detected in 66.7% of epithelioid MPM, 87.5% of biphasic MPM and 100% of sarcomatoid cases, highlighting potential utility in the differentiation of MPM from FP. Hida et al 55 performed BAP1 and p16 FISH in 40 cases of MPM and 20 cases of inflammatory pleuritis. All inflammatory cases and only three mesothelioma cases were negative for both.…”

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review

“…Both p16 (locus 9p21) and BAP1 (locus 3p21.2) are frequently deleted in malignant lesions, and they have never been reported as altered in benign lesions. Therefore, they have 100% specificity for MPM; however, their sensitivity ranges between 43-93% and 61-67% for p16 and BAP1, respectively (33)(34)(35). Combination of the two assays has been reported to increase sensitivity for MPM diagnosis up to 90% in some studies; however, specificity is always 100% (29,33,36).…”

“…Therefore, they have 100% specificity for MPM; however, their sensitivity ranges between 43-93% and 61-67% for p16 and BAP1, respectively (33)(34)(35). Combination of the two assays has been reported to increase sensitivity for MPM diagnosis up to 90% in some studies; however, specificity is always 100% (29,33,36). Moreover, BAP1 and p16 have been specifically investigated for the discernment between sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis.…”