A cancers that develops within the pancreas falls into two major categories: (1) cancers of the endocrine pancreas (the part that makes insulin and other hormones) are called "islet cell" or "pancreatic neuroendocrine tumors or PNETs" and (2) cancers of the exocrine pancreas (the part that makes enzymes). Islet cell cancers are rare and typically grow slowly compared to exocrine pancreatic cancers. Islet cell tumors often release hormones into the bloodstream and are further characterized by the hormones they produce (insulin, glucagon, gastrin, and other hormones). Cancers of the exocrine pancreas (exocrine cancers) develop from the cells that line the system of ducts that deliver enzymes to the small intestine and are commonly referred to as pancreatic adenocarcinomas. Squamous cell pancreatic cancer is rare. Adenocarcinoma of the pancreas comprises most all pancreatic ductal cancers and is the main subject of this review.Cells that line the ducts in the exocrine pancreas divide more rapidly than the tissues that surround them. For reasons that we do not understand, these cells can make a mistake when they copy their DNA as they are dividing to replace other dying cells. In this manner, an abnormal cell can be made. When an abnormal ductal cell begins to divide in an unregulated way, a growth can form that is made up of abnormal looking and functioning cells. The abnormal changes that can be recognized under the microscope are called "dysplasia." Often, dysplastic cells can undergo additional DNA mistakes over time and become even more abnormal. When these dysplastic cells invade through the walls of the duct from which they arise into the surrounding tissue, the dysplasia has become a cancer.In a study published in 2016, researchers reported analysis of the genes in 456 pancreatic ductal adenocarcinomas. Subsequent expression analysis of these adenocarcinomas allowed them to be defined into four subtypes. These subtypes have not been previously discerned. The subtypes include:
Squamous: These tumors have enriched TP53 and KDMA mutations.
Pancreatic progenitor: These tumors express genes involved in pancreatic development such as FOXA2/3, PDX1, and MNX1.
Aberrantly differentiated endocrine exocrine (ADEX): These tumors display the genes (KRAS) and exocrine (NR5A2 and RBPJL) plus endocrine (NEUROD1 and NKX2-2) differentiation.
Immunogenic: These tumors contain pathways that are involved in acquired immune suppression.
These new findings may allow future patients to be treated more specifically depending on their subtype and, hopefully, more effectively. For example, the immunogenic subtype could possibly respond to therapy where the immune system is re-engineered to attack these types of cancer cells.Pancreatic cancer should not be confused with the term pancreatitis. Pancreatitis is simply defined as inflammation of the pancreas and is mainly caused by alcohol abuse and /or gallstone formation (about 80% to 90%). Nevertheless, chronic pancreatitis is associated with pancreatic cancer.