Abstract
Mesothelin (MSLN) represents an attractive molecule for targeted cancer therapies. To identify tumors that might benefit from such therapies, tissue microarrays including 15,050 tumors from 122 different tumor types and 76 healthy organs were analyzed for MSLN expression by immunohistochemistry. Sixty-six (54%) tumor types showed at least occasional weak staining, including 50 (41%) tumor types with at least one strongly positive sample. Highest prevalence of MSLN positivity had ovarian carcinomas (serous 97%, clear cell 83%, endometrioid 77%, mucinous 71%, carcinosarcoma 65%), pancreatic adenocarcinoma (ductal 75%, ampullary 81%), endometrial carcinomas (clear cell 71%, serous 57%, carcinosarcoma 50%, endometrioid 45%), malignant mesothelioma (69%), and adenocarcinoma of the lung (55%). MSLN was rare in cancers of the breast (7% of 1138), kidney (7% of 807), thyroid gland (1% of 638), soft tissues (0.3% of 931), and prostate (0 of 481). High expression was linked to advanced pathological tumor (pT) stage (p < 0.0001) and metastasis (p < 0.0001) in 1619 colorectal adenocarcinomas, but unrelated to parameters of malignancy in 1072 breast-, 386 ovarian-, 174 lung-, 757 kidney-, 171 endometrial-, 373 gastric-, and 925 bladder carcinomas. In summary, numerous important cancer types with high-level MSLN expression might benefit from future anti-MSLN therapies, but MSLN’s prognostic relevance appears to be limited.
Highlights
The normal tissue tissue microarray (TMA) was composed of 8 samples from 8 different donors for each of 76 different normal tissue types (608 samples on one slide)
On the normal tissue TMA, a sufficient number of samples was always interpretable per tissue to determine MSLN expression
The strongest MSLN expression was observed in the squamous epithelium of tonsil crypts (Figure 1A), where a fraction of cells showed strong (+++) MSLN staining
Summary
The mesothelin (MSLN) gene, located at chromosome 16p13.3, encodes for a membranous precursor glycoprotein that is subsequently cleaved into the soluble 31kD protein megakaryocyte potentiating factor (MPF) and the 40kD membrane-bound protein. MSLN [1,2,3]. MSLN was first described as a membrane protein expressed in normal and neoplastic mesothelial cells, but subsequent studies demonstrated a broader expression pattern [1,4,5,6,7,8,9]. The function of MSLN is not fully understood. MSLN does not seem to be essential as a homozygous MSLN mutant mouse lacking MSLN protein
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