Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma

Abstract

The biological potential of soft tissue leiomyosarcoma is difficult to predict using current standard prognostic parameters, and control of systemic disease is challenging with current chemotherapeutic protocols. Additional prognostic markers and alternative treatment options are very much required. Previous studies implicate upregulation of the oncogenic nuclear transcription factor c-Myc with aggressive behavior of many solid tumors. Therefore, this oncoprotein was evaluated as a prognostic marker for overall and metastasis-free survival in leiomyosarcoma. Immunohistochemical stains for c-Myc were performed on 28 cases of leiomyosarcoma occurring in the deep somatic soft tissues. Comparisons of Kaplan-Meier survival curves stratified by c-Myc status and conventional prognostic factors (histological grade, tumor size, and tumor stage) were evaluated using standard univariate statistical methods. A subsequent multivariate survival analysis was carried out according to the Cox proportional hazards regression model adjusting for potential confounding prognostic factors. A total of 15 cases (54%) were positive for nuclear c-Myc expression. Patients with c-Mycpositive tumors had significantly shorter metastasis-free survival intervals compared with those with c-Mycnegative tumors (median, 9 months vs. 494 months; P ¼ 0.014). c-Myc positivity also correlated with decreased overall survival (median, 23 months vs. 494 months; P ¼ 0.017). Histological grade was the only other prognostic marker predictive of poor outcome in the univariate analyses. In the multivariate survival analysis, only c-Myc status reached statistical significance, suggesting that it is an important and independent predictor of prognosis in leiomyosarcoma. Detection of nuclear c-Myc in leiomyosarcoma predicts decreased overall and metastasis-free survival, independent of standard prognostic variables, tumor size, histological grade, and TNM stage. The expression of this oncoprotein may represent a useful prognostic marker and potential therapeutic target in leiomyosarcoma.

Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases

“…13 In regard to soft tissue sarcomas, MYC overexpression and increased MYC copy numbers are frequent in high-grade chondrosarcomas, 14 epithelioid sarcomas of the proximal type, 15 in higher-grade myxoid liposarcomas, 16 and have an adverse prognostic impact in leiomyosarcomas of soft tissues. 17 A recent study reported MYC high-level gene amplification in postradiation cutaneous angiosarcomas and in chronic lymphedema-associated cutaneous angiosarcomas (so-called secondary angiosarcomas), whereas so-called primary angiosarcomas of skin, soft tissues, bone, and visceral organs were negative. 6 Interestingly, high-level amplification of MYC was found in 55% of secondary angiosarcomas in this study and was not associated with tumor grade and clinical prognosis.…”

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

“…The c-myc protein is a transcription factor that regulates many downstream factors responsible for cell cycle progression and apoptosis. Over the past couple decades, the oncogenic properties of c-myc have been described in a wide variety of malignancies [7][8][9][10]. Aberrations deregulating c-myc transcription have been implicated in many hematologic malignancies, especially Burkitt lymphoma and diffuse large Bcell lymphoma (DLBCL) [11,12].…”

Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

“…It is necessary to select the appropriate therapy for patients with STSs due to their different pathobiological behavior and prognostic significance. A number of prognostic or biological markers were studied in STSs and reported to be significant prognostic markers (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”