PanNETs : Chromogranin
Immunohistochemistry of Pancreatic Neuroendocrine Tumors (PanNETs) - continued from the previous image. PanNETs may also express PDX-1, PAX8, and ISL1. NETs from different sites (GI, pancreas, lung etc.) vary in their expression of transcription factors and other markers. In a patient with metastatic NET, an immunohistochemical panel may be helpful in identifying the primary site. PanNETs are ISL1 +ve; pulmonary tumors are CK7+ve and TTF1+ve; and gastrointestinal tumors are CDX2+ve and CK20+ve. About 45% of NF-PanNETs have mutually exclusive mutations in DAXX or ATRX genes leading to loss of nuclear expression of these markers. Usually, there is no overexpression of p53 or loss of expression of RB1 or SMAD4. PanNETs in the setting of von Hippel-Lindau disease show expression of HIF1A and CAIX. About this image: It shows immunoreactivity for chromogranin in a PanNET. Chromogranins are water-soluble acidic glycoproteins that are present in most neural and endocrine tissues. PanNETs frequently produce chromogranin which can be detected immunohistochemically or by measuring blood levels. Plasma chromogranin A (CgA) levels are elevated in >90% of PanNETs. However, the lack of high sensitivity and specificity limits the usefulness of CgA levels as a tumor marker.