Transducin-Like Enhancer of Split-3 (TLE3) Is Differentially Expressed in Angiosarcomas (AS) of Sporadic Cutaneous, Sporadic Soft Tissue/Visceral and Post-Irradiation Types: A Study of 100 Cases.
Wonwoo Shon, Douglas T Ross, Robert S Seitz, Rodney A Beck, Brian Z Ring, Scott H Okuno, Andrew L Folpe. Mayo Clinic, Rochester, MN; Clarient Inc., Aliso Viejo, CA
Background: TLE3, a member of the transducin-like enhancer of split (TLE) family of proteins, is a transcriptional repressor that interacts with the Notch/WNT pathway. Recently, expression of TLE3 has been associated with improved outcome in breast cancer patients treated with taxanes. As taxanes are also commonly used for the treatment of AS, we investigated the frequency of TLE3 expression in a large series of these sarcomas.
Design: All available materials from 100 AS (38 cutaneous (AS-C), 49 soft tissue/visceral (AS-STV), and 13 post-irradiation (AS-PRT) were retrieved. Follow-up (F/U) was obtained. Formalin-fixed, paraffin-embedded sections were immunostained for TLE3 (monoclonal, 1:2000, Clarient) using heat-induced epitope retrieval and the Bond polmer refine detection system. Nuclear immunoreactivity was scored as "negative" (<5% positive cells) and "positive" (>5% positive cells). Appropriate controls were employed. Fisher's exact and Kaplan-Meier tests were performed.
Results: Cases occurred in 51F and 49M (median age 64 yrs; range 3 mos-90 yrs). AS-C most often involved the head/neck, AS-STV occurred in a variety of soft tissue/visceral locations, AS-PRT involved breast skin. Overall, 33/100 (33%) AS were TLE3+. TLE3 expression was strongly associated with AS subtype, with expression in 0/38 (0%) AS-C, 29/49 (59%) AS-ST and 4/13 (31%) AS-PRT (p<0.001). TLE3 expression was significantly more common in poorly differentiated (epithelioid or spindled) AS (24/56, 43%) vs well-differentiated (vasoformative) AS (9/44, 20%). Clinical F/U was available on 86/100 (86%) patients (31 dead of disease, 7 dead of other causes, 24 dead of unknown cause, 24 alive without disease; median 65 mos, range 35-250 mos). 20 patients were known to have been treated with a taxane. No differences in survival were seen in TLE3+ vs TLE3- AS, whether treated with a taxane or not.
Conclusions: Expression of TLE3 is present in up to one-third of AS, most often poorly differentiated, non-vasoformative AS-STV. Surprisingly, TLE3 expression is not seen in AS-C, possibly reflecting the different pathogenesis (sun exposure) of this subset of AS. Alternatively, TLE3 expression could represent a late event in AS, accounting for its more frequent expression in generally larger and more poorly differentiated AS-STV. Although we did not find a statistically significant relationship between TLE3 expression and survival or taxane response, these issues should be investigated in a larger, prospective study.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 23, Tuesday Morning