Cadherin-17 (CDH17) expression in human cancer: A tissue microarray study on 18,131 tumors.

Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. CDH17 is therefore considered a possible diagnostic and therapeutic target. This study was to comprehensively determine the expression of CDH17 in cancer and to further assess the diagnostic utility of CDH17 immunohistochemistry (IHC). A tissue microarray containing 14,948 interpretable samples from 150 different tumor types and subtypes as well as 76 different normal tissue types was analyzed by IHC. In normal tissues, a membranous CDH17 staining was predominantly seen in the epithelium of the intestine and pancreatic excretory ducts. In tumors, 53 of 150 analyzed categories showed CDH17 positivity including 26 categories with at least one strongly positive case. CDH17 positivity was most common in epithelial and neuroendocrine colorectal neoplasms (50.0%-100%), other gastrointestinal adenocarcinomas (42.7%-61.6%), mucinous ovarian cancer (61.1%), pancreatic acinar cell carcinoma (28.6%), cervical adenocarcinoma (52.6%), bilio-pancreatic adenocarcinomas (40.5-69.8%), and other neuroendocrine neoplasms (5.6%-100%). OnIy 9.9% of 182 pulmonary adenocarcinomas were CDH17 positive. In colorectal adenocarcinomas, reduced CDH17 staining was linked to high pT (p = 0.0147), nodal metastasis (p = 0.0041), V1 (p = 0.0025), L1 (p = 0.0054), location in the right colon (p = 0.0033), and microsatellite instability (p < 0.0001). The CDH17 expression level was unrelated to tumor phenotype in gastric and pancreatic cancer. In summary, our comprehensive overview on CDH17 expression in human tumors identified various tumor entities that might often benefit from anti-CDH17 therapies and suggest utility of CDH17 IHC for the distinction of metastatic gastrointestinal or bilio-pancreatic adenocarcinomas (often positive) from primary pulmonary adenocarcinomas (mostly negative).

Prostein expression in human tumors: a tissue microarray study on 19,202 tumors from 152 different Tumor entities.

BACKGROUND: Prostein (P501S), also termed solute carrier family 45 member 3 (SLC45A3) is an androgen regulated protein which is preferentially expressed in prostate epithelial cells. Because of its frequent expression in prostate cancer, prostein was suggested a diagnostic prostate cancer marker. METHODS: In order to comprehensively assess the diagnostic utility of prostein immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. RESULTS: Prostein immunostaining was typically cytoplasmic, granular and perinuclear. Prostein positivity was seen in 96.7% of 419 prostate cancers including 78.3% with strong staining. In 16,709 extra-prostatic tumors, prostein positivity was observed in 7.2% of all cases but only 0.3% had a strong staining. Overall, 50 different extra-prostatic tumor categories were prostein positive, 12 of which included at least one strongly positive case. Extra-prostatic tumors with highest rates of prostein positivity included different subtypes of salivary gland tumors (7.6-44.4%), neuroendocrine neoplasms (15.8-44.4%), adenocarcinomas of the gastrointestinal tract (7.3-14.8%), biliopancreatic adenocarcinomas (3.6-38.7%), hepatocellular carcinomas (8.1%), and adenocarcinomas of other organs (up to 21%). CONCLUSIONS: Our data provide a comprehensive overview on prostein expression in human cancers. Prostein is a highly sensitive prostate cancer marker occurring in > 96% of prostate cancers. Because prostein can also be expressed in various other tumor entities, classifying of a tumor mass as a prostate cancer should not be based on prostein positivity alone.

CELA3B immunostaining is a highly specific marker for acinar cell carcinoma of the pancreas.

Chymotrypsin-like elastase family member 3B (CELA3B, elastase-3B) is a pancreatic enzyme with digestive function in the intestine. Since RNA analyses of normal tissues suggest that CELA3B expression is limited to the pancreas, the potential diagnostic utility of CELA3B immunohistochemistry for the distinction of pancreatic from extrapancreatic cancers and in the distinction of acinar cell carcinoma from ductal adenocarcinoma was assessed. CELA3B expression was successfully analyzed in 13,223 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types by immunohistochemistry in a tissue microarray format (TMA). In normal tissues, CELA3B immunostaining was only seen in acinar cells and in a fraction of ductal cells of the pancreas as well as on some apical membranes of surface epithelial cells of the intestine. Among tumors, CELA3B immunostaining was seen in 12 of 16 (75%) acinar cell carcinoma of the pancreas including 6 cases with strong staining (37.5%) as well as in 5 of 13,207 other tumors (0.04%). These included 1.2% of 91 adenoid cystic carcinomas, 1.2% of 246 mucoepidermoid carcinomas and 0.8% of 127 acinic cell carcinomas of salivary glands. Our data show a good sensitivity (75%) and a high specificity (99.9%) of CELA3B immunohistochemistry for diagnosing acinar cell carcinoma of the pancreas.

Cytokeratin 13 (CK13) expression in cancer: a tissue microarray study on 10,439 tumors.

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1-92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1-77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed - a usually weak - CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p < 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p = 0.0295) and shortened recurrence-free (p = 0.0094) and overall survival (p = 0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p = 0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors.