Dudnik E.*, Kuten J., Haim N.*, Shulman K.*, Ben-Itzhak O. †, Ilan N.††, Vlodavsky I.††

1. Plasma Levels of Heparanase as Marker of Tumor Aggressiveness and Stage of Disease in Patients with Colorectal Cancer Dudnik E.*, Kuten J., Haim N.*, Shulman K.*, Ben-Itzhak O.†, Ilan N.††, Vlodavsky I.†† *Division of Oncology, Rambam Health Care Campus, Haifa, Israel; † Pathology Department, Rambam Health Care Campus, Haifa, Israel; ††Cancer and Vascular Biology Research Center,The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Table 2. Relationship between plasma heparanase level and clinico-pathological characteristics. Background Heparanase enzyme upregulation was documented in large number of tumors, including colorectal cancer, and is associated with increased tumor aggressiveness. Objectives • To evaluate plasma heparanase level in colorectal cancer pts, as a screening tool for diagnosis and disease monitoring; • To examine the correlation between plasma heparanase levels and clinical and pathological parameters, such as tumor burden and response to antineoplastic treatments. Table 1. Plasma heparanase levels according to the activity of disease. Patients and Methods • Plasma heparanase levels were assessed in 92 colorectal cancer pts, treated at the Division of Oncology, Rambam Health Care Campus. • The pts were divided into 3 groups, according to their tumor burden. • Group 1: comprised of 47 pts with recurrent or metastatic disease. In this group blood samples were collected at the start of treatment and at restaging. • Group 2: included 27 pts without evidence of disease up to 6 months after surgery. • Group 3: included 18 pts without evidence of disease at least two years after surgery. • Plasma heparanase was measured by ELISA. Results † for the difference between 1metastatic lesion vs. 2-3 metastatic lesions;† † for the difference between 1metastatic lesion vs. >3 metastatic lesions;† † † for the difference between 2-3metastatic lesions vs. >3 metastatic lesions • The mean serum heparanase concentration in the first sample of the entire population was 179.6 ± 595.3 pg/ml. • In the 1st, 2nd and 3d group of pts the mean plasma heparanase levels were 221.9±703.8 pg/ml (n-47), 28.3±102.6 pg/ml (n-27), and 295.8±696.4 pg/ml (n-18), respectively. • There was a trend for higher mean serum heparanase levels among pts with active disease in comparison to pts without evidence of disease (Table 1). Picture 1. The relationship between plasma heparanasealterations and response to treatment. pts, n • Smoking history (p=0.004), lymph node sampling (p=0.02), and oxaliplatin-based chemotherapy (p=0.007) were independent predictors of plasma heparanaselevels in univariateanalysis • (Table 2). • A trend for higher serum heparanase concentration among pts with metastatic disease (p=0.2), and high grade tumors (p=0.3) was observed (Table 2). • A trend for lower plasma heparanase concentration in oligometastatic disease (p=0.08) was observed (Table 2). • A non-significant correlation between response to treatment and plasma heparanase alterations was observed (p=0.18) (Picture 1). Conclusion • A positive, but non-significant correlation between plasma heparanase level and tumor aggressiveness and response to treatment in pts with colorectal cancer was observed. • Smoking history, lymph node sampling, and oxaliplatin-based chemotherapy were independent predictors of plasma heparanase level. • Larger study is required in order to validate plasma heparanase as a marker of colorectal cancer aggressiveness. Contact information: Elizabeth Dudnik, M.D., Division of Oncology, Rambam Health Care Campus, Haifa, Israel E-mail: e_dudnik@rambam.health.gov.il