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Insulin-Like Growth Factor Type 1 Receptor Expression Correlates to Good Prognosis in Highly Malignant Soft Tissue Sarcoma

Departments of ¹ Molecular Medicine, ² Surgery, ³ Orthopedics, and ⁴ Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden

Requests for reprints: Jan Åhlén, Department of Molecular Medicine, CMM L8:01, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Phone: 46-8-51773616; Fax: 46-8-51776180; E-mail: jan.ahlen{at}kirurgi.ki.se.

Purpose: To evaluate known and suggested prognostic markers, especially insulin-like growth factor type 1 receptor (IGF-1R), in highly malignant soft tissue sarcomas (STS).

Experimental Design: A cohort of 101 patients with primary STS of high malignancy grade was studied with respect to development of metastasis, local recurrence, and survival during a minimum of 5 years follow-up. All tumors were analyzed by immunohistochemistry for expression of Ki-67, p53, p27, Bcl-2, IGF-1R, and microvessel density. The traditional clinical variables size, malignancy grade (3 or 4), necrosis, mitotic frequency, infiltrative tumor growth, vascular invasion, depth, and surgical margins were also evaluated.

Results: A significant association was shown between high expression of IGF-1R and favorable outcome. Among STS with positive IGF-1R immunoreactivity, cases with high expression (76-100% positive cells) had the best outcome, whereas cases with the lowest expression (1-25% positive cells) had the worst. As expected, large tumor size (>11 cm), presence of necrosis, high mitotic count, intralesional surgery, and deep location were all significantly associated with poor outcome, both in univariate and multivariate analyses. No difference in outcome was observed between cases of malignancy grade 3 versus 4, whereas the included and more objective variables necrosis and mitotic count were found to be reliable prognostic markers.

Conclusion: IGF-1R expression is a common feature of highly malignant STS. Further elucidation of the role of IGF-1R and the IGF system in STS may both provide a basis for development of new prognostic tools in STS, as well as shed light on the basic mechanisms of the STS development.

Key Words: soft tissue sarcoma • immunohistochemistry • IGF-1R • vessel density • tumor size • malignancy grade • prognosis

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