Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study

Abstract

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with a poor survival. Although some advances in knowledge have been obtained for the pleural form, much less is known about DMPM. Advantages in terms of prognosis are still limited and strong efforts need to be made. The aim of our study was to correlate several histological and molecular factors with survival in a large cohort of 45 DMPMs. We evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, desmoplastic reaction, Ki67 percentage, WT-1 expression, p16 protein by immunohistochemistry and CDKN2A deletion by FISH. Our results showed that epithelioid histotype, nuclear grade 2, mitotic count ≤5 x mm2, absence of desmoplasia and p16/CDKN2A deletion, low Ki67 value, and high WT-1 expression were correlated with the most prolonged survival (p = 0.0001). Moreover, p16 loss in immunohistochemistry reflected CDKN2A deletion detected with FISH, and both were correlated with the worst survival (p = 0.0001). At multivariate analysis, Ki67 value, WT-1 expression and p16/CDKN2A deletion emerged as independent prognostic factors (p = 0.01, p = 0.0001 and p = 0.01, respectively). These parameters are easy to analyse at the time of DMPM diagnosis and may support better patient stratification, prediction of treatment effectiveness and therapeutic optimization.

Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature

“…More recently, the loss of immunohistochemical expression of BAP1 has been suggested to strongly support the diagnosis of mesothelioma in women presenting with abdominal disease [ 113 , 125 , 126 ]. Ito et al [ 130 ] proposed the detection of the homozygous deletion of p16/CDKN2A (p16) by FISH as an effective tool for the diagnosis of malignant mesothelioma, which is now also considered a prognostic factor [ 30 ]. Moreover, new chromosomal mutations in mesothelioma have also been suggested as sensitive and specific diagnostic tools in mesothelioma [ 131 ].…”

“…Immunohistochemical analyses were carried out using the Envision Detection System (Dako, Glostrup, Denmark) with diaminobenzidine (DAB) as chromogenic substrate, on the Dako Techmate automatic stainer (Carpinteria, CA, USA). For fluorescence in situ hybridization (FISH) analysis, the FISH locus specific CDKN2A (9p21) probe (Abbott, Abbott Park, IL, USA) was used, as previously described [ 30 ].…”

A Single Liver Metastasis from Pleural Biphasic Mesothelioma

“… In our patient, the combination of different immunohistochemical markers, together with the detection of p16/CDKN2A deletions, most frequently reported in mesotheliomas [ 1 , 16 ], permitted a confident identification of the mesothelial lineage of the neoplastic cells. …”

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

“…Those two markers, BAP1 and p16, result exclusively unexpressed or deleted only in MPM. Considering that BAP1 and p16 are not deleted in all MPMs and their sensitivity can variate between 43% and 93% for p16 and 61-67% for BAP1, negative results can sometimes be inconsistent in order to exclude the malignancy [204,217,218]. Therefore, these markers may be not specific to MPM, but may aid diagnosis and may have prognostic significance [216][217][218].…”