Abstract
Syndecan-1 (CD138) is a transmembrane proteoglycan known to be expressed in various normal and malignant tissues. It is of interest because of a possible prognostic role of differential expression in tumors and its role as a target for indatuximab, a monoclonal antibody coupled with a cytotoxic agent. To comprehensively analyze CD138 in normal and neoplastic tissues, we used tissue microarrays (TMAs) for analyzing immunohistochemically detectable CD138 expression in 2,518 tissue samples from 85 different tumor entities and 76 different normal tissue types. The data showed that CD138 expression is abundant in tumors. At least an occasional weak CD138 immunostaining could be detected in 71 of 82 (87%) different tumor types, and 58 entities (71%) had at least one tumor with a strong positivity. In normal tissues, a particularly strong expression was found in normal squamous epithelium of various organs, goblet and columnar cells of the gastrointestinal tract, and in hepatocytes. The highly standardized analysis of most human cancer types resulted in a ranking order of tumors according to the frequency and levels of CD138 expression. CD138 immunostaining was highest in squamous cell carcinomas such as from the esophagus (100%), cervix uteri (79.5%), lung (85.7%), vagina (89.7%) or vulva (73.3%), and in invasive urothelial cancer (76.2%). In adenocarcinomas, CD138 was also high in lung (82.9%) and colorectal cancer (85.3%) but often lower in pancreas (73.3%), stomach (54.2% in intestinal type), or prostate carcinomas (16.3%). CD138 expression was usually low or absent in germ cell tumors, sarcomas, endocrine tumors including thyroid cancer, and neuroendocrine tumors. In summary, the preferential expression in squamous cell carcinomas of various sites makes these cancers prime targets for anti-CD138 treatments once these might become available. Abundant expression in many different normal tissues might pose obstacles to exploiting CD138 as a therapeutic target, however.
Highlights
Syndecan-1 (CD138) is one of four members of the syndecan family
The results of this study provide a comprehensive overview on Syndecan-1 expression in human tumors
Even though adenocarcinomas derived from the colon and the lung are high expressers, CD138 immunostaining appears to be generally less intense and less frequent in adenocarcinomas
Summary
Syndecan-1 (CD138) is one of four members of the syndecan family. Syndecan-1 has relevance for cell-cell and cell-matrix interactions [1]. It is involved in the regulation of cell proliferation, migration, and the Disease Markers organization of the cytoskeleton [1]. In a phase II trial on plasmocytoma, clinical efficacy and low side effects have been reported [2, 3]. In preclinical studies, these antibodies showed efficacy against triple negative breast cancer and melanoma [4, 5]. If anti-CD138 therapies should prove successful, other CD138-positive cancer types might as well benefit from such treatments
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