New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet?
BACKGROUND
The separation of benign from malignant mesothelial proliferations is crucial to patient care but is frequently morphologically difficult.


OBJECTIVE
To briefly review adjunctive tests claimed to be useful in this setting and to examine in detail 2 new tests: p16 fluorescence in situ hybridization (FISH) and BRCA1-associated protein 1 (BAP1) immunohistochemistry.


METHODS
Literature review with emphasis on p16 FISH and BAP1 immunohistochemistry.


RESULTS
Glucose transporter-1, p53, insulin-like growth factor 2 messenger RNA-binding protein 3 (IMP-3), desmin, and epithelial membrane antigen have all been claimed to mark either benign or malignant mesothelial processes, but in practice they at best provide statistical differences in large series of cases, without being useful in an individual case. Homozygous deletion of p16 by FISH or loss of BAP1 has only been reported in malignant mesotheliomas and not in benign mesothelial proliferations. BAP1 appears to be lost more frequently in epithelial than mixed or sarcomatous mesotheliomas. Homozygous deletion of p16 by FISH is seen in pleural epithelial, mixed, and sarcomatous mesotheliomas, but it is much less frequent in peritoneal mesothelioma. The major drawback to both these tests is limited sensitivity; moreover, failure to find p16 deletion or BAP1 loss does not make a mesothelial process benign.


CONCLUSIONS
In the context of a mesothelial proliferation, the finding of homozygous deletion of p16 by FISH or loss of BAP1 by immunohistochemistry is, thus far, 100% specific for malignant mesothelioma. The limited sensitivity of each test may be improved to some extent by running both tests.
Andrew
A
Churg
Brandon S
BS
Sheffield
From the Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada (Drs Churg and Sheffield); and Service Anatomie Pathologique, Centre National Référent MESOPATH, CHU du Caen, Caen, France (Dr Galateau-Salle). Dr Galateau-Salle is now with the Department of Pathology, Centre Leon Berard, Lyon, France.
Francoise
F
Galateau-Salle
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003937:Diagnosis, Differential; D004848:Epithelium / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000473:pathology*; D008654:Mesothelioma / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000473:pathology*; D010994:Pleura / Q000473:pathology; D010997:Pleural Neoplasms / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism
C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018396:Mucin-1; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase