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
Background
Table 2. Relationship between plasma heparanase level and clinico-pathological characteristics.
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.
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
• 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).
Serum heparanase, pg/ml,
mean ± SD
p value
Smoking
Current/former smokers
Never smokers
449.7±807.0
111.5±579.7
0.004
Chemotherapy regimen
Oxaliplatin-based treatment
Other treatment regimens
31.1±96.1
270.7±740.3
LN sampling
≥12 LN
<12 LN
173.8±515.0
81.3±186.6
M Stage
MO
M1
138.1±454.8
220.9±711.5
Extent of the disease
1 metastatic lesion
2-3 metastatic lesions
>3 metastatic lesions
104.3±59.5
172.6±295.6
250.5±808.1
Histological Grade
Low Grade
Intermediate Grade
High Grade
98.3±242.7
194.6±516.1
317.9±1095.6
0.007
0.02
0.2
0.5†
0.08††
0.4†††
0.32
† 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
Picture 1. The relationship between plasma heparanase alterations and response to treatment.
pts, n
Table 1. Plasma heparanase levels according to the activity of disease.
Serum heparanase, pg/ml, mean ± SD
Group 1: active disease,
n-47
Group 2+3: w/o evidence of
disease ,
n-45
p value
221.9±703.8
135.3±459.5
0.1
• Smoking history (p=0.004), lymph node sampling (p=0.02), and oxaliplatin-based chemotherapy
(p=0.007) were independent predictors of plasma heparanase levels in univariate analysis
(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).
Contact information:
Elizabeth Dudnik, M.D., Division of Oncology,
Rambam Health Care Campus, Haifa, Israel
E-mail: e_dudnik@rambam.health.gov.il
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.