Prognostic Significance of c-Myc Expression in Soft Tissue Leiomyosarcoma
AC Tsiatis, ME Herceg, SJ Olson, HS Schwartz, GE Holt, JM Cates. Johns Hopkins University, Baltimore, MD; Vanderbilt University Medical Center, Nashville, TN; Vanderbilt Orthopaedic Institute, Nashville, TN
Background: Decreased expression of integrin 7 has been correlated with shorter disease-free survival in soft tissue leiomyosarcoma (LMS). However, use of this marker in routine surgical pathology practice is precluded by the lack of a commercially available antibody for use on formalin-fixed, paraffin-embedded tissue. Other recent data has implicated the oncogenic nuclear transcription factor c-Myc as a direct inhibitor of integrin 7 gene expression. Therefore, we determined whether c-Myc might be a surrogate prognostic marker for decreased integrin 7 expression in LMS.
Design: Immunohistochemical stains for c-Myc were performed on 29 cases of high-grade soft tissue LMS. Tumors were scored as positive for c-Myc expression if >10% of lesional cells demonstrated specific nuclear staining. Comparison of Kaplan-Meier overall and disease-free survival curves was performed using the log rank test. Other clinicopathologic parameters (patient age, sex, tumor size, AJCC TNM stage, and p53 status) were compared using standard univariate statistical methods.
Results: 14 of the 29 LMS samples (48%) were positive for nuclear c-Myc staining. Overall survival for patients with c-Myc-positive tumors (median 22.7 months) was significantly decreased compared to patients with c-Myc-negative tumors (median 75.5 months; p=0.015). C-Myc positivity was also associated with shorter disease-free survival (median 8.8 months, compared to 25.1 months for c-Myc-negative tumors; p=0.006). C-Myc status did not correlate with patient age, sex, tumor size, AJCC TNM stage, or p53 status.
Conclusions: Detection of nuclear c-Myc in soft tissue LMS predicts decreased overall and disease-free survival. These results are consistent with previous experimental data showing poor outcomes in LMS patients with decreased integrin 7 expression, since c-Myc inhibits transcription of this integrin gene. Thus, c-Myc status may be a useful prognostic marker and potential therapeutic target in soft tissue LMS.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 19, Monday Afternoon