Posters— Surgical Treatment of Sarcomas

THE PREDICTIVE VALUE OF TISSUE TRAN- GLUTAMINASE IN MALIGNANT FIBROUS HISTIOCYTOMA

Heiner JP, Hughes EM, Aeschlimann D, Hafez R, Kehoe R. (University of Wisconsin, Madison, WI, 53792)

Introduction: Transglutaminase is a family of calcium dependent enzymes which act by catalyzing the cross-linking of proteins during the formation of N- glutamyl-1ysy1 bond between two peptide chains, and through G protein mediated activation in normal tissues. Great interest in tTGase has come about because of its implicated role in apoptosis, cell adhesion, tumor growth and differentiation and invasive/metastatic behavior. Malignant Fibrous Histiocytoma is thought to be the most common soft tissue sarcoma of late adult life. Although several other factors have also been investigated, prognosis for these tumors has been largely based on size of tumors and grade. Initial treatment is typically wide surgical resection and radiation therapy. The aim of our study was to determine if tTGase has predictive value for metastatic disease or local recurrence in MFH to better identify those patients that may benefit from adjuvant chemotherapy.

Methods: This is a retrospective study using pathologic specimens previously obtained from 1988-1999 in-patients diagnosed with MFH. Twenty-three patients in this time period for which we have adequate non-irradiated tissue are included in the study. Thirteen subjects were male nine females. Paraffin fixed pathologic specimens were collected underwent deparafination and immunohistochemical staining as previously described by Aeschliman.1 After staining with the monoclonal antibody was complete the, stains for each tumor were graded on a 0-3 scale by 2 separate observers, blinded to each other’s results. A retrospective review was performed of patients charts as well as through telephone contact for those patients which had limited follow up. Information on size of tumor, histologic grade, dates of recurrence of metastatic disease and death were recorded. Biostatistical analysis was performed to evaluate the relationship of size, grade, age and tTGase average rating to disease free survival. This was done in a multivariate and univariate fashion utilizing Kaplan Meier regression curves.

RESULTS: Average follow-up was 40 months (range 4-126 months). 8/23 had no local recurrence or metastatic disease, 2/23 had local recurrence, and 14/23 had metastatic disease. Univariate analysis demonstrated no statistically significant difference for disease free survival based on age or histologic grade. Disease free survival for those with a size of = 10 cm was significantly shorter (p<0.01) with a median disease free survival of ~ 3 months vs. ~ 3 years for those < 10 cm. Additionally those with a higher (>1) tTGase average score had a significantly shorter (p~0.02) disease free survival of ~ 4 months vs. 2 years for those £ 1. However, when tTgase was corrected for tumor size a trend (p£0.09) was seen for tTgase score in multivariate analyses.

DISCUSSION: Tissue transglutaminase has been shown to be involved in programmed cell death, cell matrix stabilization and cell adhesion. We found that a higher tTgase (p~0.02) may be associated with a poorer outcome. These people may benefit from adjuvant chemotherapy but otherwise wouldn’t have previously been identified to be in a higher risk group. A larger study with more statistical power is needed to determine if the association found here is significant.