Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma.(Statistical Data Included)

Abstract

Background and aims--Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps.

Methods--Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy. The range of normality for faecal calprotectin (0.5-10.5 mg/1) was determined from 96 healthy subjects.

Results--Median faecal calprotectin concentration in the 62 patients with colorectal carcinoma (101 mg/1, 95% confidence interval (CI) 57-133) differed significantly from normal (2.3 mg/1, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal [less than]10 mg/1) whereas only 36/62 (58%) had positive faecal occult bloods. There was no significant difference in faecal calprotectin levels when considering location or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was significantly higher for Dukes' stage C and D cancers compared with Dukes' A and B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in whom the median faecal calprotectin was 12 mg/1 (95% CI 2.9-32). Sensitivity for detection of adenomatous polyps was 55% using the calprotectin method and 10% using faecal occult blood testing. The overall sensitivity and specificity of calprotectin for colorectal cancer and adenomatous polyps as a combined group was 79% and 72%, respectively, compare d with a sensitivity and specificity of faecal occult blood of 43% and 92%.

Conclusions--Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.

(Gut 2001;49:402-408)

Keywords: colorectal cancer; faecal occult blood testing; calprotectin

Colorectal cancer is the second commonest cause of death from malignancy in the Western world. In the USA it accounts for 14% of cancer deaths with about 134 000 colorectal cancer registrations and 55 000 deaths each year [1] while in the UK there are an annual 28 000 cancer registrations and 19 000 deaths due to this disease. [2] Survival rates are closely related to the stage of cancer at the time of diagnosis and the most promising approach to reducing mortality rates is early detection of precancerous or cancerous lesions. There is now overwhelming epidemiological evidence and molecular biological data to substantiate previous suggestions of the colonic adenomacarcinoma progression. [3-5] Collectively, such data have increased the pressure to develop novel approaches for colon cancer detection, critical for secondary prevention through mass population screening whereby early diagnosis of colorectal cancer will detect tumours with the best prognosis and result in improved survival rates.

The most widely accepted non-invasive method for detecting colorectal cancer is faecal occult blood (FOB) testing. Screening in asymptomatic populations have, at best, reduced mortality rates by 15-33% [6-8] There are however many problems with screening using FOB. The sensitivity of the most commonly used guaiac based FOB tests may be as low as 26% [9] which means that 74% of patients with malignant lesions will remain undetected by this method, presumably because blood loss from the tumour may be intermittent or below the detection threshold (2-4 ml of blood/l00 g stool). The test may also not be suitable for screening of precancerous adenomas which often do not bleed. [10 11] There are also practical difficulties with certain types of FOB tests which require patients to provide three stool samples while subject to some dietary restrictions. [12-14]

In order to increase the detection rate, clinicians have sought alternative methods for detection of early colorectal cancer/adenomas. A large trial of flexible sigmoidoscopy (compromising the non-invasive nature of investigation) in an asymptomatic population is now underway in the USA [15] and the UK [16] to assess whether this will lead to significantly improved survival for colorectal cancer, but are not expected to yield results until 2008, while flexible sigmoidoscopy is now widely used as an initial examination in symptomatic patients.

Colorectal cancer is associated with a local acute inflammatory reaction so that in some cases it can be visualised by white cell neutrophil scanning. [17] Calprotectin is a stable neutrophil specific marker which can be assayed in stool with high precision and ease. [18] Within the neutrophil calprotectin is found in the extra lysosomal cytosol and constitutes up to 60% of the total protein content. [19] Levels of faecal caiprotectin are increased in patients with colorectal cancer but immunohistochemical examination of colorectal cancer specimens has shown reactivity confined to neutrophilic granulocytes with no reactivity seen in neoplastic cells, [20-22] suggesting that elevated faecal levels may be due to neutrophil shedding from an ulcerated tumour. The purpose of this study was to assess whether faecal calprotectin is an improvement on the sensitivity and specificity of FOB in current use as a non-invasive biochemical marker for colorectal cancer and colorectal polyps.

Patients and methods

AIMS

The aims of the study were to (i) assess and compare the sensitivity of faecal calprotectin and FOB for colorectal carcinoma in symptomatic patients with colorectal cancer and relate the results to cancer site or degree of invasion; (ii) assess and compare the sensitivity of the two tests for colorectal polyps subsequently found at colonoscopy; and (iii) assess and compare the specificity of the two tests for detecting colorectal cancer/premalignant polyps.

PATIENTS

Ninety six healthy volunteers (51 males, 45 females, mean age 41 years) provided single …