J Cancer 2014; 5(9):784-789. doi:10.7150/jca.9485 This issue

Research Paper

The Cause and Prevention of Anastomotic Recurrence following Colectomy: An Immunohistochemical Approach for Detecting Transforming Colonocytes

M. Arlen1,3✉, J. Crawford2, G. Coppa1, O. Saric3, J. Bandovic2, A. Doubakovski3, J. Sullivan1, C. Conte1, A. Kadison1, J. Procaccino1, P. Arlen3, X. Wang3, E. Molmenti1

1. Dept. Surgery NSUH, Manhasset NY, USA;
2. Dept. Pathology NSUH, Manhasset NY, USA;
3. Dept. Precision Biologics, Great Neck NY, USA.

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Arlen M, Crawford J, Coppa G, Saric O, Bandovic J, Doubakovski A, Sullivan J, Conte C, Kadison A, Procaccino J, Arlen P, Wang X, Molmenti E. The Cause and Prevention of Anastomotic Recurrence following Colectomy: An Immunohistochemical Approach for Detecting Transforming Colonocytes. J Cancer 2014; 5(9):784-789. doi:10.7150/jca.9485. Available from https://www.jcancer.org/v05p0784.htm

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With the ability to identify the presence of transforming colonocytes in a field adjacent to an existing primary colon cancer, it is now possible to reduce if not eliminate one of the major causes leading to anastomotic tumor recurrence. In a review of those colectomy cases that presented post-surgery with anastomotic recurrence, we noted that mucosal abnormalities could readily be detected adjacent to the primary lesion. Such changes had gone unrecognized at the time of surgery, when standard histologic procedures were employed. By utilizing monoclonal antibodies (mAbs) that defined the presence of tumor immunogenic proteins, we were able to reexamine so-called normal biopsy sites adjacent to the tumor. Here, it was possible to demonstrate the presence of altered cellular activity in existing phenotypically normal appearing colonocytes that were in the process of transforming to malignancy.

Eight consecutive patients that had been admitted for evaluation and resection of an anastomotic recurrence post colectomy, were studied with regard to possible etiologic factors. The original margins incorporated into the anastomosis were re-examined by immunohistochemistry employing those monoclonal antibodies (mAbs) designed to target colon tumor antigen. This antigen had previously been shown to be expressed only in colon cancer and not in adjacent normal tissue. In addition, biopsies from margins of resection in five patients free of recurrence following colectomy were also studied along with colon specimens from 50 normal patients, non-demonstrating expression of tumor antigen in the normal appearing colonocytes.

In each of the patients who had presented with anastomotic recurrence, normal appearing colonocytes defined by light microscopy and found adjacent to the previously resected primary lesion, expressed tumor antigen. The antigen detected in these colonocytes proved to be identical to antigen expressed in the anastomotic recurrence giving credence to the concept that these normal appearing cells in proximity to the tumor were responsible for the regrowth of tumor in the suture line used to establish continuity of the bowel.

Based on the findings of this preliminary retrospective study it is felt that at the time of performing a colectomy for a malignant lesion of the bowel, that it is important that those normal appearing colonocytes adjacent to tumor be evaluated for expression of tumor associated antigen. Excluding such cells from an anastomosis, may help to assure that tumor recurrence will be minimized if not totally eliminated.

Keywords: Anastomotic recurrence, immunohistochemistry, monoclonal antibodies, colon tumor antigen.