Brief Article
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World J Gastroenterol. May 7, 2014; 20(17): 4994-4999
Published online May 7, 2014. doi: 10.3748/wjg.v20.i17.4994
Clinical and histopathological correlations of fecal calprotectin release in colorectal carcinoma
Frank Serge Lehmann, Francesca Trapani, Ida Fueglistaler, Luigi Maria Terracciano, Markus von Flüe, Gieri Cathomas, Andreas Zettl, Pascal Benkert, Daniel Oertli, Christoph Beglinger
Frank Serge Lehmann, Christoph Beglinger, Division of Gastroenterology and Hepatology, University Hospital, 4031 Basel, Switzerland
Francesca Trapani, Luigi Maria Terracciano, Institute of Pathology, University Hospital, 4003 Basel, Switzerland
Ida Fueglistaler, Markus von Flüe, St. Clara Hospital, 4016 Basel, Switzerland
Gieri Cathomas, Institute of Pathology, University Hospital, 4410 Liestal, Switzerland
Andreas Zettl, Institute of Pathology, Viollier AG, 4002 Basel, Switzerland
Pascal Benkert, Clinical Trial Unit, University Hospital, 4031 Basel, Switzerland
Daniel Oertli, Department of Surgery, University Hospital, 4031 Basel, Switzerland
Author contributions: All authors had contributed significantly, were in agreement with the content of the manuscript, read and approved the final manuscript. Lehmann FS, Terracciano LM and Beglinger C participated in study conception and design, acquisition, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and having full access to all of the data in the study and taking responsibility for the integrity of the data and the accuracy of the data analysis; Benkert P was involved in the study design and performed the statistical analysis; Trapani F performed all histopathological studies; Fueglistaler I, von Flüe M, Cathomas G, Zettl A and Oertli D participated in acquisition of data and revised the manuscript for intellectual content.
Supported by Unrestricted research grants to Dr. Lehmann FS by the Freiwillige Akademische Gesellschaft (Basel, Switzerland); and the Pfizer AG, Viollier Laboratories AG, Switzerland performed the fecal calprotectin assays
Correspondence to: Frank Serge Lehmann, MD, Division of Gastroenterology and Hepatology, University Hospital, Petersgraben 4, 4031 Basel, Switzerland. fslehmann@hin.ch
Telephone: +41-61-4210232 Fax: +41-61-4210274
Received: May 27, 2013
Revised: September 4, 2013
Accepted: September 16, 2013
Published online: May 7, 2014
Abstract

AIM: To determine calprotectin release before and after colorectal cancer operation and compare it to tumor and histopathological parameters.

METHODS: The study was performed on patients with diagnosed colorectal cancer admitted for operation. Calprotectin was measured in a single stool sample before and three months after the operation using an enzyme-linked immunosorbent assay (ELISA). Calprotectin levels greater than or equal to 50 μg/g were considered positive. The compliance for collecting stool samples was assessed and the value of calprotectin was correlated to tumor and histopathological parameters of intra- and peri-tumoral inflammation. Surgical specimens were fixed in neutral buffered formalin and stained with hematoxylin and eosin. Staging was performed according to the Dukes classification system and the 7th edition tumor node metastasis classification system. Intra- and peri-tumoral inflammation was graded according to the Klintrup criteria. Immunohistochemical quantification was performed for MPO, CD45R0, TIA-1, CD3, CD4, CD8, CD57, and granzyme B. Statistical significance was measured using Wilcoxon signed rank test, Kruskal Wallis test and Spearman’s rank correlation coefficient as appropriate.

RESULTS: Between March 2009 and May 2011, 80 patients with colorectal cancer (46 men and 34 women, with mean age of 71 ± 11.7 years old) were enrolled in the study. Twenty-six patients had rectal carcinoma, 29 had left-side tumors, 23 had right-side tumors, and 2 had bilateral carcinoma. In total, 71.2% of the patients had increased levels of calprotectin before the operation (median 205 μg/g, range 50-2405 μg/g) and experienced a significant decrease three months after the operation (46 μg/g, range 10-384 μg/g, P < 0001). The compliance for collecting stool samples was 89.5%. Patients with T3 and T4 tumors had significantly higher values than those with T1 and T2 cancers (P = 0.022). For all other tumor parameters (N, M, G, L, V, Pn) and location, no significant difference in calprotectin concentration was found. Furthermore, the calprotectin levels and histological grading of both peri- and intra-tumoral inflammation was not correlated. Additional testing with specific markers for lymphocytes and neutrophils also revealed no statistically significant correlation.

CONCLUSION: Fecal calprotectin decreases significantly after colorectal cancer operation. Its value depends exclusively on the individual T-stage, but not on other tumor or histopathological parameters.

Keywords: Calprotectin, Colorectal cancer, Inflammation, Tumor size, Granulocytes

Core tip: Colorectal cancer (CRC) patients have a significant increase of fecal calprotectin release. The mechanisms for this observation are unclear. In our study, we examined the calprotectin release before and after operation of 46 CRC patients. This is the first study that assessed the correlation of calprotectin with both tumor as well as histopathological parameters. Our study contains the following new information: (1) the release of calprotectin is exclusively correlated to the T-stage, but to no histopathological parameters; and (2) except the T-stage, all other tumor characteristics assessed by the seventh edition of the tumor node metastasis classification are not correlated.