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Glycoprotein Biomarkers for Malignancy in Pancreatic Cysts

We speak of pancreatic cancer as if it is one thing, but there are many kinds of pancreatic cancer; one classification had this number at 17.  A frequent anatomic / physiologic action of the pancreas is that it tends to produce cysts (and sometimes even “pseudocysts” – pockets of fluid often seen as a result of pancreatitis).  Many of these cysts are benign, but some percentage are or become malignant. It is often difficult to differentiate between the innocent cystic structures, and ones that may become serious current or future problems.

Unexpected findings have become an increasingly frequent issue, as our ever advancing radiographic tools have progressed to a point where they often identify troubling elements in the pancreas (or elsewhere) which were not the target of the initial procedure – but now which we are must deal with in terms of their clinical significance – for the long-term good of the patient, and their peace of mind.  The clever term has arisen for these unexpected findings: radiological “incidentalomas.” Pancreatic cysts then are often incidentalomas – requiring an element of diagnosis and explanation.

Also until now, carcinoembryonic antigen levels (CEA) – including the knowledge of its limitations – was often considered the general marker of choice for this task; a high level tending to point toward malignancy. We should also here begin to discuss individual “mucins” that are glycoproteins related to a series of a “family” of about twenty MUC genes. These mucins tend to line the surface of epithelial cells found in human lung, GI tract, eye, and other organs. Several of the MUC proteins have found to be overexpressed in colon, breast, ovarian, lung and pancreatic cancers.

Now comes a clever study by Jabbar and colleagues from University of Gothenburg, Sweden who published their results in the February 2014 issue of the Journal of the National Cancer Institute, outlining their work in utilizing mucin proteomics as a biomarker process to differentiate benign pancreatic cysts from those that may become precursors of pancreatic cancer.

Over about a five-year period of time (2007-2012) the authors evaluated 102 patients with what appeared to be pancreatic cysts, ultimately including 91 patients in their study who met their established inclusion criteria. The researchers then used endoscopic ultrasound to aspirate contents of the cysts, examining the extract for cytological (cell) changes, CEA levels, and individual MUC (mucin) levels including a panel of mucins. They found that MUC1, MUC2, and MUC5AC particularly appeared to identify cysts with potential for pancreatic cancer malignancy.

The results of this study were that mucin proteomic profiling (97.5%) was a more accurate method of identifying malignancy potential than either CEA levels (78.0%), or cytology (71.4%).  The authors suggest that proteomic biomarkers involving a panel of mucin glycoproteins appear to be a promising manner of differentiating benign cycts from those with malignant potential for pancreatic cancer. This is a highly persuasive study that requires confirmation.


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Dale O’Brien, MD