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.

Biophysical Approaches for the Characterization of Protein-Metabolite Interactions.

With an estimate of hundred thousands of protein molecules per cell and the number of metabolites several orders of magnitude higher, protein-metabolite interactions are omnipresent. In vitro analyses are one of the main pillars on the way to establish a solid understanding of how these interactions contribute to maintaining cellular homeostasis. A repertoire of biophysical techniques is available by which protein-metabolite interactions can be quantitatively characterized in terms of affinity, specificity, and kinetics in a broad variety of solution environments. Several of those provide information on local or global conformational changes of the protein partner in response to ligand binding. This review chapter gives an overview of the state-of-the-art biophysical toolbox for the study of protein-metabolite interactions. It briefly introduces basic principles, highlights recent examples from the literature, and pinpoints promising future directions.

Diagnostic and prognostic role of pancreatic secretory granule membrane major glycoprotein 2 (GP2) immunohistochemistry: A TMA study on 27,681 tumors.

Pancreatic secretory granule membrane major glycoprotein 2 (GP2) is a membrane component of zymogen granules which is abundantly secreted by pancreatic acinar cells. Because RNA based analyses suggest a strict limitation of GP2 expression to the pancreas in normal tissues, and a strong preference to pancreatic cancer among tumors, GP2 expression analysis might have diagnostic utility. To better understand the role of GP2 protein expression, GP2 was successfully analyzed in 27,965 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). GP2 immunostaining was seen in 14 of 16 (87.5 %) acinar cell carcinomas, 6 of 507 (1.2 %) ductal adenocarcinomas, and 3 of 99 neuroendocrine neoplasms of the pancreas (3.0 %). GP2 was also found in 23 extra-pancreatic tumor entities including several types of neuroendocrine neoplasms (14.3-58.8 %), prostatic adenocarcinomas (8.2-18.8 %), various other adenocarcinomas (0.1-7.7 %), and several categories of benign and malignant salivary gland tumors (2.3-3.1 %). A strong GP2 positivity was only seen in 6 tumor categories including 50 % of 16 pancreatic acinus cell carcinomas, 11.8 % of 17 neuroendocrine tumors of the lung, 1.3 % of 80 primary Gleason 4 + 4 % and 0.6 % of 181 recurrent prostate cancers, as well as 0.8 % of 133 adenocarcinomas of the lung. In a cohort of 14,747 prostate cancers with follow up data, GP2 immunostaining was strongly linked to advanced pT stage, high Gleason grade, lymph node metastasis, and recurrence free survival (p < 0.0001 each). The prognostic impact of GP2 positivity was independent of established parameters in TMPRSS2:ERG fusion-negative cancers (p < 0.0001). In summary, our data show that GP2 is preferentially expressed in acinar cell carcinomas of the pancreas but the glycoprotein can - rarely - also be expressed in a variety of other tumor entities.