Heparinase-1 Expression Is Progressively Increased with Increasing Stage in Non-Small Cell Lung Carcinoma and May Help Predict Recurrence in Early Stage Non-Small Cell Lung Cancer
AT Howard, JA Weber, AW Kim, X Xu, MJ Liptay, P Gattuso. Rush Medical Center, Chicago, IL
Background: Heparinase-1 (HPR1) is an endoglucuronidase that cleaves heparin sulfate proteoglycans, a main constituent in basement membrane (BM) and extracellular matrix (ECM). HPR1 promotes tumor metastasis by breaking down the BM and ECM. We studied HPR1 expression in non-small cell lung cancer (NSCLC) and its clinicopathologic significance.
Design: Paraffin-embedded surgical specimens from 54 patients with primary NSCLC were analyzed (37 adenocarcinomas and 17 squamous cell carcinomas). Twenty-eight specimens were stage I. Nineteen specimens were from patients with ipsilateral hilar node metastases--stage II disease. Seven specimens were from patients with locoregionally advanced stage III disease, 3 of which were treated with neoadjuvant chemotherapy/radiation. All specimens were stained for HPR1 expression (positive defined as >10% staining, with increasing intensity scored from 0 to 4 with 4 being the most intense).
Results: Twenty-one of 28 stage I specimens expressed HPR1 (mean intensity 1.62). Among these 21, recurrence occurred in 5 patients (24%). Among the 7 negative specimens, only 1 patient (14%) developed recurrence. Ten of 19 stage II specimens expressed HPR1 (mean intensity 1.92). Among these stage II specimens, recurrence occurred in 3 of the 10 patients with positive specimens (30%) and in none of the patients with negative specimens. Although not statistically significant, the disease-free survival for HPR1 positive tumors was lower than for HPR1 negative tumors (p=0.14). Three of 4 stage III specimens without neoadjuvant therapy were positive for HPR1 expression (mean intensity 2.3). The 3 stage III specimens with neoadjuvant therapy were negative. HPR1 staining intensity was not significantly different between stages, although the difference approached significance between non-neoadjuvant and neoadjuvant stage III specimens (p=0.6).
Conclusions: HPR1 expression appears to increase with increased stage, which may reveal the mechanism behind tumor metastasis. Neoadjuvant therapy may modify the role of HPR1 in metastases as evidenced by decreased expression in treated specimens. Recurrence appears to be higher in patients expressing HPR1. Patterns of recurrence were more erratic in stage III NSCLCs, but this may be due to patient heterogeneity and small sample size.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 228, Tuesday Afternoon