2001 CTOS Annual Meeting Posters— Biology

EXPRESSION OF OSTEOPONTIN AND HGF/SF-MET IN ADULT SOFT TISSUE SARCOMA
Stewart C. Rorke¹,  Vivien H. Bramwell¹,  Ann F. Chambers¹,  Alan B. Tuck²,  Larry Stitt^3
1London Regional Cancer Centre,  ²London Health Sciences Centre,  ³University of Western Ontario

METHODS: Thirty-three tissue samples from ASTS were obtained from a cohort of patients registered in the Canadian Soft Tissue Sarcoma Tumor Bank/Correlative Clinical Data Base. OPN and Met expression were determined by semiquantitative immunohistochemistry. Results were expressed as a total score derived from a combination of intensity (0-3) and proportion (0-5) of staining, for a potential total out of 8.

RESULTS: Included in the cohort were 8 superficial and 27 deep tumours, with a median maximum diameter of 9 cm. There were 33 primary tumours and 1 local recurrence. Most common among a wide range of histologies were malignant fibrous histiocytoma (9), liposarcoma (7), and leiomyosarcoma (6). Number of patients with grades 1, 2, 3-4 were 5, 13, and 12 respectively (not available (N/A) in 3 patients). UICC clinical stage (at the time of sample submission):I(6), II (14), III (6), IV (3), N/A (4). Surgeries included: amputation (2), local marginal resection (22), and wide resection (9). Adjuvant chemotherapy and radiation was given in 4 and 15 patients respectively. Two patients received neoadjuvant chemotherapy. Median follow-up time was 40 months (range 2-84 months) and the 2-year overall survival was 69%. Mean OPN and Met scores were 2.8 and 1.4 respectively. Scores ranged from 0 to 7 in OPN and 0 to 6 in Met, with standard deviations of 2.2 and 2.0 respectively. With respect to OPN score, Spearman correlation coefficients for stage and grade were 0.479 (p=0.009) and 0.500 (p=0.005) respectively, indicating strong positive associations. Univariable Cox regression analysis showed that increasing OPN levels predict decreased disease-free survival (DFS) (Hazard ratio (HR) = 1.55, (95% CI:1.15-2.10), p=0.003). Similarly, OPN was significantly associated with decreased overall survival (OS)(HR=1.31, (95% CI: 1.006-1.714), p=0.045). Met scores were not significantly associated with outcome.

CONCLUSION: In this small retrospective analysis of an ASTS cohort : (1) Increased OPN expression (determined immunohistochemically) was associated with decreased DFS and OS. (2) Level of Met expression was not significantly associated with outcome. There are many potential pitfalls in analysis of marker expression in small inhomogeneous cohorts of patients, and these findings need to be explored in a larger series of ASTS cases.