Calprotectin is a protein released by neutrophils, a type of white blood cell, when the lining of the digestive tract becomes inflamed. When inflammation occurs in the intestines, neutrophils migrate to the area and shed this protein into the stool. Measuring Fecal Calprotectin (FCP) is a non-invasive way to assess the presence and severity of inflammation within the bowel. This measurement is a reliable biomarker used to differentiate between inflammatory and non-inflammatory conditions.
Establishing Calprotectin Baseline Levels
Interpreting a Fecal Calprotectin test result relies on established numerical thresholds, typically measured in micrograms per gram (\(\mu \text{g/g}\)) of stool. The first zone is considered a normal or low-risk range, generally defined as less than \(50 \mu \text{g/g}\) in adults. A result in this range strongly suggests that symptoms are likely due to a non-inflammatory disorder, such as Irritable Bowel Syndrome (IBS).
The second zone is an intermediate or “gray area,” usually falling between \(50 \mu \text{g/g}\) and \(150 \mu \text{g/g}\). This level indicates a mild or low-grade inflammation, but it is often not high enough to definitively diagnose a major inflammatory condition. In this intermediate range, a physician may recommend re-testing in several weeks to see if the level drops back to normal or rises further.
The third zone, indicating significant or high elevation, is typically defined as a result greater than \(150 \mu \text{g/g}\) or \(200 \mu \text{g/g}\). This high elevation suggests active, organic inflammation within the gastrointestinal tract, necessitating further investigation to determine the exact cause. A high result signifies significant inflammation but does not specify the underlying disease.
Non-Cancer Causes of Elevated Calprotectin
Elevated Fecal Calprotectin is a general marker for bowel inflammation. Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and Ulcerative Colitis, is the most recognized cause of sustained, high FCP levels. Patients with active IBD often show levels that exceed \(250 \mu \text{g/g}\), sometimes reaching values in the thousands. The severity of the inflammation in IBD often correlates directly with the height of the FCP value.
Acute gastrointestinal infections, such as bacterial gastroenteritis or viral infections, also cause a temporary but significant spike in calprotectin. Unlike chronic conditions like IBD, these infection-related elevations usually resolve as the infection clears.
Certain medications can also induce inflammation and elevate FCP levels, particularly Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen or aspirin. These drugs can irritate the intestinal lining, causing mild mucosal damage and leading to a measurable increase in calprotectin. Other non-malignant conditions, including diverticulitis, microscopic colitis, and celiac disease, are also known to cause elevated FCP readings.
How Calprotectin Levels Inform Cancer Investigation
FCP is an inflammation marker, not a tumor marker. There is no specific numerical threshold that automatically means a diagnosis of Colorectal Cancer (CRC). However, extremely high and sustained FCP levels necessitate immediate investigation, as cancer is one of the possible underlying causes of severe inflammation.
Colorectal tumors, especially advanced ones, cause local inflammation, ulceration, and bleeding as they grow, which triggers the influx of neutrophils. This local inflammatory response is what elevates the FCP measurement in many CRC patients. Studies have shown that FCP levels tend to be significantly higher in patients with CRC compared to healthy individuals and may correlate with more advanced stages of the disease.
The primary clinical utility of FCP in the cancer investigation process is its high Negative Predictive Value (NPV). A low or normal FCP result, typically below \(50 \mu \text{g/g}\), makes the presence of significant organic disease like IBD or CRC highly unlikely. This allows clinicians to safely rule out the need for an invasive procedure like a colonoscopy in many symptomatic patients. For patients with symptoms suggestive of CRC, a normal FCP level permits a less urgent management approach.
Conversely, an elevated FCP level, especially one that is significantly high, acts as a filter to identify patients who have an organic disease and urgently require a colonoscopy. The colonoscopy visually determines the precise cause of the inflammation, which could be cancer, an aggressive form of IBD, or another severe inflammatory condition. Therefore, the level does not diagnose cancer, but rather dictates the urgency of the necessary follow-up procedure that provides the definitive diagnosis.