Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma

Abstract

Importance Vascular leiomyosarcomas (vLMS) are a rare subtype of leiomyosarcomas (LMS) most commonly affecting the inferior vena cava and accounting for 5% of all LMS. These tumors are aggressive malignancies for which adjuvant modalities have not shown increased efficacy compared over surgery. Our study evaluates potential molecular markers that should be evaluated in prospective studies to determine their prognostic and therapeutic utility. Objective To evaluate the outcomes of patients with vLMS and associations with immunohistochemical prognostic markers. Design Retrospective chart review Setting Single institution Participants A cohort of 77 patients that presented to MDACC from 1993–2012 was analyzed. All of the cases had a confirmed diagnosis of vascular leiomyosarcoma. Immunohistochemical studies for biomarkers were performed on a tissue microarray that included 26 primary vLMS specimens. Main Outcomes and Measures Demographic, and clinical factors were evaluated to assess clinical course, patterns of recurrence and survival outcomes for patients with primary vLMS. Univariate Cox proportional hazards model was utilized to correlate DSS and time to recurrence with potential prognostic indicators. Results Five year disease-specific survival (DSS) rates after tumor resection was 65%. Median time to local recurrence was 43 months, versus 25 months for distant recurrence versus 15 months for concurrent local and distant recurrences; p=0.04. Strong cytoplasmic β-catenin (p=0.06) and IGF-1R (p=0.04) expression were associated with inferior DSS. Conclusions and Relevance vLMS are aggressive malignancies, with high recurrence rates. Expression of β-catenin and IGF-1R were associated with poor DSS. Prospective studies should evaluate their clinical and therapeutic utility.

Pulsed Dye Laser Treatment Combined with Oral Minocycline Reduces Recurrence Rate of Rosacea

“…Time to recurrence was measured from the date of the treatment termination to first re-visit or to last follow-up. The recurrence rate was estimated using the Kaplan-Meier method, and difference of the recurrence rates between two groups was compared using the log-rank test 13 14 . Each variable which showed a significant difference between two groups was evaluated in the simple Cox proportional hazards model.…”

Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience

“…Development of LMS is characterized by the presence of complex and unbalanced karyotypes, resulting in genomic instability associated with multiple gene aberrations such as TP53, RB1, CDKN2A, IGFR, and PTEN [6,[29][30][31]. These gene aberrations subsequently cause the activations of corresponding signaling pathways such as the RB1/ cyclin D1, p53/MDM2, PI3K/AKT/mTOR, and IGFR/AKT pathways, which provided potential targets for future drug development [32][33][34][35].…”

“…LMS is relatively rare representing 10–20% of soft tissue sarcomas . It can appear at almost all anatomic sites such as the uterus , retroperitoneum , extremities , and blood vessels . Uterine LMS is the most common site‐specific group with an estimated incidence of 0.64 cases per 100,000 women .…”

Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors

“…The following expression levels were significantly higher in leiomyosarcomas than in PTSMT (Table 2 ): WNT9B, GAS1, signaling factor desert hedgehog (DHH), the two Notch signaling pathway factors LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase provided (LFNG) and MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase (MFNG), protein kinase cAMP-activated catalytic subunit alpha (PRKACA) and insulin-like growth factor 1 (IGF1). Roland et al [ 10 ] showed that leiomyosarcomas also express the IGF receptor which indicates paracrine activation.…”

“…The fact that many canonical WNT signaling factors were not increased and that we found no nuclear beta-catenin indicates activation of the non-canonical WNT pathway. Similar to PTSMT, leiomyosarcomas usually show no aberrant nuclear beta-catenin expression [ 10 , 16 ]. Non-canonical WNT signaling is often characterized by alternative signaling without cytoplasmic stabilization of soluble beta-catenin [ 17 – 19 ].…”