RT Journal Article
SR Electronic
T1 OP015/#492 Further stratification of no specific molecular profile (NSMP/P53WT) endometrial carcinomas to refine prognosis and identify therapeutic opportunities
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP A17
OP A17
DO 10.1136/ijgc-2021-IGCS.32
VO 31
IS Suppl 4
A1 E Thompson
A1 J Huvila
A1 D Chiu
A1 S Leung
A1 A Lum
A1 A Jamieson
A1 M Köbel
A1 M Plante
A1 S Scott
A1 S Salvador
A1 D Vicus
A1 L Helpman
A1 M Kinloch
A1 K Grondin
A1 J Irving
A1 A Talhouk
A1 D Huntsman
A1 S Kommoss
A1 C Gilks
A1 J Mcalpine
YR 2021
UL http://ijgc.bmj.com/content/31/Suppl_4/A17.1.abstract
AB Objectives Molecular classification identifies >50% of endometrial cancers (ECs) as having ‘no specific molecular profile/NSMP’; without mismatch repair deficiency, p53 IHC abnormalities, or pathogenic POLE mutations. Clinical presentation and outcomes within NSMP ECs are diverse and optimal treatment unclear with new ESMO/ESTRO/ESP guidelines unchanged for this molecular subtype. Better biomarkers are needed to predict if and what adjuvant therapies are needed.Methods We characterized the clinicopathological and molecular (IHC+NGS) profiles of 1047 NSMP ECs in women from population-based and institutional cohorts, testing for associations with treatment response and outcomes.Results Key pathologic and molecular features associated with survival parameters (p<0.01) are tabulated below. 31% of NSMP ECs had CTNNB1 mutations, however, associations with outcomes (PFS) were observed only within Gr1/2 early-stage endometrioid ECs(p=0.03), or if restricted to ECs without substantial LVI or L1CAM overexpression (p< 0.005). TP53 mutations (with normal p53IHC) were discovered in 41 women with a trend (p=0.06) to worse survival. On multivariable analysis only grade (3vs.1/2) maintained significance. 8% of this cohort would be eligible for current molecular classification de-escalation trials. Treatment received did not impact survival within low-, intermediate-, or high-intermediate risk NSMP ECs. Within high-risk, the most favorable outcomes were observed in women who received pelvic radiation with no observed benefit of chemotherapy.View this table:Abstract OP015/#492 Table 1 Conclusions Additional prognostic stratification of NSMP ECs can be achieved with both pathologic and molecular features. Further study within NSMP subgroups may identify conventional, hormonal or targeted therapies that are more effective.