Heparanase-1 Expression in Carcinoid Tumors
Naris Nilubol1, todd Beyer1, Carmen C. Solorzano1, Paolo Gattuso2, Xiulong Xu1, Richard Prinz1; 1General Surgery, Rush University, chicago, IL; 2Pathology, Rush University Medical Center, Chicago, IL
Introduction Heparanase-1 (HPR) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a major component of the extracellular matrix (ECM) and basement membrane. Expression of HPR is associated with tumor invasion and metastasis. HPR expression has been demonstrated in a number of tumors including neuroendocrine tumors such as pheochromocytoma. This study evaluates whether HPR is expressed in carcinoid tumors and assesses whether HPR expression correlates with carciniod tumor invasiveness. Methods The paraffin-embedded blocks from 59 patients who had carcinoid tumors biopsied or removed from 1993 to 2004 were analyzed. Patient charts and pathology reports were reviewed. HPR expression was determined by immunohistochemistry(IHC) using a rabbit anti-HPR antibody. All slides were reviewed and the intensity of the staining was graded by a single pathologist. Fisher’s Exact Test was used to compare invasive and metastatic tumors to non-invasive tumors. Results There were 26 males and 33 females with a mean age of 56 years (range 19-89 years). There were 20 bronchial carcinoids, 16 small bowel carcinoids, 13 rectal, 6 colonic and 4 carcinoid tumors from other sites. Thirty six patients had localized tumors, 10 had lymph node metastasis and 13 had distant metastasis. Forty seven of 59 tumors (80%) had HPR expression on IHC. Sixteen of 18(88.2%) localized carcinoid tumors that invaded muscularis propria and/or mucosa expressed HPR. Nineteen of 23 tumors (82.6%) with lymph node and/or distant metastasis had HPR expression. Seven of 13 (53.8%) with localized tumors without invasion expressed HPR. Five patients had an endoscopic biopsy and depth of invasion could not be assessed. Invasive and metastatic carcinoid tumors had significant higher HPR expression than non-invasive tumors(35 of 41 versus 7 of 13, p=0.03). Conclusion Most carcinoid tumors express HPR. Invasive and metastatic carcinoid tumors have significantly greater HPR expression than non-invasive tumors. HPR expression may be useful in predicting aggressive tumor behavior.
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