[679] Cadherin Expression in Gastrointestinal Tract Endometriosis: Possible Role in Deep Tissue Invasion and Development of Malignancy

KE Van Patten, V Parkash, D Jain. Yale University School of Medicine, New Haven, CT

Background: Cadherins are cell surface proteins crucial for cell adhesion and tissue integrity. Studies of peritoneal endometriosis have shown decreased E-cadherin and -catenin expression with preserved N-cadherin expression. We recently encountered a case of carcinoma arising in colonic endometriosis that showed total loss of N-cadherin, but preserved E-cadherin and -catenin expression in the tumor. The mechanism of deep tissue invasion in gastrointestinal (GI) endometriosis is unknown and may be related to the expression of these cell surface proteins. The goal of this study was to evaluate the expression of E-cadherin, -catenin and N-cadherin in GI endometriosis.
Design: Cases of GI endometriosis identified from our pathology database were included in the study. The histopathology was reviewed and the anatomic site and extent of involvement was recorded for each case. Immunohistochemistry was performed using antibodies against N-cadherin, E-cadherin, and -catenin on 4- formalin-fixed paraffin-embedded representative tissue sections from each case. Cases of normal endometrium (n=5) and adenomyosis (n=6) were also included in the study for comparison. The intensity of staining for each marker was scored subjectively on a scale of 0 to 3 and the number of glands staining was scored from 0 to 4 (0 = none, 1 = 1 to 24%, 2 = 25 to 49%, 3 = 50 to 74%, 4 = 75 to 100%). Appropriate positive and negative controls were used.
Results: Twenty-one cases of GI endometriosis were included in the study (colon=11, appendix=8, small bowel=2). The endometriosis was seen infiltrating up to mucosa (n = 1), submucosa (n = 7), muscularis propria (n = 10) and only serosa (n = 3). Significantly decreased N-cadherin expression (3=0, 10=1+) was found in 13 (61.9%) cases of GI endometriosis compared to controls. Two of 3 cases involving only the serosa showed strong diffuse N-cadherin staining as has been previously reported in peritoneal endometriosis, while distinct and marked loss of N-cadherin was seen in the more deeply invasive lesions that extended into muscularis propria, submucosa or mucosa. Moderate to strong membranous staining for -catenin expression was diffusely present in all cases. Variable intensity of E-cadherin expression was also seen diffusely in all cases.
Conclusions: These results strongly suggest that loss of N-cadherin in GI endometriosis may play an important role in the mechanism that underlies deep tissue invasion, and possibly also in the development of malignancy.
Category: Gastrointestinal

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 108, Monday Morning