Mesothelin is a
differentiation antigen that was first described as the antigenic target of the
monoclonal antibody K1. Using this antibody, it was demonstrated that
mesothelin is strongly expressed in normal mesothelial cells,
mesotheliomas, nonmucinous ovarian
carcinomas, and some other
malignancies. Immunostaining with the K1 antibody was suggested to be useful in the diagnosis of
mesothelioma in the early 1990s. This, however, could not be further explored until recently because of the lack of commercially available anti-
mesothelin antibodies. In a recent investigation by this author, all epithelioid
mesotheliomas and about 40% of the
lung adenocarcinomas reacted with the 5B2 anti-
mesothelin antibody, which has only recently become commercially available. It was concluded that immunostaining with this antibody has limited value in discriminating between these conditions. The aim of the current study was to further investigate the potential application of the 5B2 antibody in
tumor diagnosis.
Mesothelin expression was evaluated in
formalin-fixed,
paraffin-embedded samples of normal tissues and in 471
tumors of various origins. The
carcinomas that most frequently exhibited strong
mesothelin reactivity were nonmucinous
carcinomas of the ovary (14 of 14 serous, 3 of 3 endometrioid, 6 of 8 clear cell, and 4 of 4
transitional cell carcinoma), and
adenocarcinomas of the pancreas (12 of 14), the ampulla of Vater (3 of 3), endometrium (7 of 11), lung (14 of 34), and liver (7 of 19
cholangiocarcinomas). The
carcinomas that did not express
mesothelin included
renal cell carcinomas,
hepatomas,
carcinomas of the thyroid,
adrenal cortical carcinomas, prostatic
adenocarcinomas, and
carcinoid tumors. All
germ cell tumors, with the exception of
teratomas, were consistently negative for
mesothelin. Because of the strong
mesothelin expression in nonmucinous
carcinomas of the ovary, but not in a variety of
tumors with which these lesions may be confused (eg, clear cell
carcinoma of the ovary versus
endodermal sinus tumor or
renal cell carcinoma, clear cell type;
transitional cell carcinoma of the ovary versus TCC of the urinary tract), immunostaining for this marker could be useful in establishing the differential diagnosis. The strong
mesothelin expression in the large majority of pancreatic ductal
adenocarcinomas (12 of 14), but not in normal pancreas, confirms that this marker may have some diagnostic utility in discriminating between neoplastic and nonneoplastic pancreatic ductal epithelium. The
mesothelin expression in about one-third of the
cholangiocarcinomas, but not in
hepatomas, suggests that this marker may have some utility in distinguishing between these two
malignancies when they are poorly differentiated. In the group of small round blue cell
tumors, only desmoplastic small round cell
tumors exhibited
mesothelin positivity (7 of 12). Of the soft tissue
tumors, only the epithelial component of biphasic
synovial sarcomas (9 of 9) expressed
mesothelin. These findings indicate that, in some instances,
mesothelin immunostaining can assist in the diagnosis of these
tumors. Finally, the strong
mesothelin reactivity seen in the
adenomatoid tumors (3 of 3) provides further support for a mesothelial derivation for this lesion.