Uterine Leiomyosarcoma Management, Outcome, and Associated Molecular Biomarkers: A Single Institution’s Experience

Abstract

Background Uterine leiomyosarcoma (ULMS) is an aggressive, rapidly progressive tumor lacking clinical and molecular predictors of outcome. Methods ULMS patients (n = 349) were classified by disease status at presentation to MDACC as having intra-abdominal (n = 157) or distant metastatic disease (n = 192). Patient, tumor, treatment, and outcome variables were retrospectively retrieved. Formalin-fixed, paraffin-embedded tumor and control tissues from these patients (n = 109) were assembled in a tissue microarray and evaluated for hormone receptors and markers of angiogenesis, cell-cycle progression and survival. Patient, tumor, and treatment variables were correlatively analyzed. Results The 5- and 10-year disease-specific survival (DSS) for the cohort was 42 and 27 %, respectively. Patients with primary intra-abdominal tumors had better outcomes than those with recurrent intraperitoneal tumors. Whites had a more favorable prognosis. In patients with intra-abdominal tumors, only mitotic count >10M/10HPF portended poorer prognosis. Patients with pulmonary metastasis had improved outcomes with “curative” metastasectomy. ULMS samples exhibited loss of ER and PR expression, overexpressed Ki-67, and altered p53, Rb, p16, cytoplasmic β-catenin, EGFR, PDGFR-α, PDGFR-β, and AXL levels. Metastatic tumors had increased VEGF, Ki-67, and survivin expression versus localized disease. Survivin and β-catenin expression were associated with intraperitoneal recurrence; high bcl-2 expression predicted longer DSS. Conclusions Analysis of both clinicopathologic factors and immunohistochemical biomarkers in ULMS identified several prognostic clinical and molecular factors, suggesting that further study may lead to improved ULMS understanding and treatment.

Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors

“…The involvement of RB1 in pathogenesis of different malignancies as well as a role for RB1 in leiomyosarcoma is a frequent reported finding. [47][48][49] In contrast, a loss in 13q was only detected in a single leiomyoma indicating a potential use of intact RB as a surrogate marker for leiomyomas. Confirmation of this finding in a larger number and variety of leiomyomas is warranted.…”

Diagnostic and Prognostic Significance of p16, p53, and bcl-2 Expressions and Ki-67 Proliferation Index in Benign and Malignant Uterine Smooth Muscle Tumors

“…No consensus has been reached regarding the correlation between the clinical course of LMS and possible prognostic factors such as age, disease stage, tumor size, necrosis, vascular invasion, and mitotic index (2,9,(15)(16)(17). Most studies reported that tumor size and mitotic index are the most significant parameters for prognosis (2)(3)(4).…”

“…Cases were evaluated for Ki-67 PI by dividing them into two groups on the basis of whether >10% or <10% staining was observed (15). For quantitatively evaluating Ki-67 staining, the five most intensively stained areas were selected while screening HPF at 40× magnification, and the average of these values was used (16).…”

Uteri̇n Lei̇omyosarkom: 22 Olguda Patolojik Değerlendirme (Uterine Leiomyosarcoma: Pathologic evaluation of 22 Cases)

“…Lusby ve ark. 'nın ça-lışmalarına göre 5 yılık sürvinin en çok bağımlı olduğu parametre ise intraperitonealrekürrens-tir (9). LMS'larda farklı prognostik parametreler rapor edilmiştir.…”