Uroplakin-IIIb as a novel immunohistochemical marker for mesothelioma

Distinguishing mesothelioma from non-small cell lung carcinoma often requires a battery of immunohistochemical stains, as many traditional markers used in mesothelioma lack sufficient specificity to allow them to be used alone. A recent large-scale TMA screen identified uroplakin-IIIb (UpIIIb; clone MSVA-736M) as a potentially specific marker for mesothelioma. We examined the performance of this antibody using tissue microarrays containing a panel of 48 epithelioid mesotheliomas, 26 sarcomatoid mesotheliomas, and 144 non-small cell lung carcinomas (NSCLCs). Here we show that UpIIIb has good sensitivity (37/47 evaluable cases positive, 79%) and excellent specificity for distinguishing epithelioid mesothelioma from NSCLC (0/140 evaluable cases positive). UPIIIb sensitivity for epithelioid mesotheliomas was only slightly inferior to the established highly specific mesothelioma marker HEG1 (41/46 evaluable cases positive on the same TMA, 89%). However, UpIIIb did not stain any sarcomatoid mesotheliomas (0/24 evaluable cases positive). We also found that UpIIIb stained a proportion of high-grade serous ovarian carcinomas, a perennial diagnostic confounder in the context of mesotheliomas. Taken together, our data suggest that UpIIIb can be used as a highly specific and sensitive mesothelial marker when the diagnostic question is epithelioid mesothelioma versus NSCLC; in particular, UpIIIb staining will pick up some number of epithelioid mesotheliomas that are HEG1 negative. Since UpIIIb is known to stain some proportion of urothelial carcinomas as well as gynecologic and a few pancreatic tumors, it should be used with caution in the peritoneal cavity or when the differential diagnosis includes carcinomas from these locations.