MDB-55. LYMPHOID ENHANCER-BINDING FACTOR 1 (LEF1): AN IMMUNOHISTOCHEMICAL PREDICTIVE MARKER FOR WNT-ACTIVATED MEDULLOBLASTOMA

Abstract

Abstract AIM To evaluate lymphoid enhancer-binding factor 1 (LEF1) immunohistochemical expression in various molecular subtypes of medulloblastoma. MATERIALS AND METHODS Molecular subtyping of medulloblastomas was based on real-time PCR target 12 gene panel. LEF1 immunohistochemistry was performed and its expression was correlated with histological and molecular subtypes. RESULTS The study cohort included 65 cases; comprising 17 WNT-activated, 20 SHH-activated, and 28 non-WNT/non-SHH [group 3: 11, group 4: 10, non-WNT/non-SHH NOS: 7] medulloblastomas. The age range was 1-40 years (≤18 years=54 [WNTa:15, SHHa:13, non-WNT/non-SHH:26], 19-40 years=11) with a median age of 9, and an interquartile range (IQR) of 5-14.5. Forty-one were males and 24 were females (M:F=1.7:1). LEF1 immunostaining was diffuse (≥50% tumour cells) in 13 cases, focal (5-49% tumour cells) in 11 cases, and negative in 41 cases. All cases with diffuse LEF1 immunostaining (n=13) were WNT-activated with classic histology. Twelve of the 13 cases had CTNNB1 mutation on Sanger sequencing and monosomy 6 by fluorescence in-situ hybridization (FISH) while 1 case was uninterpretable for CTNNB1 Sanger sequencing and chromosome 6 FISH. LEF1 staining intensity was strong in 9 cases while heterogenous in 4 cases. No differential staining pattern was observed for paediatric and adult cases. Diffuse LEF1 immunostaining was significantly associated with the WNT-activated subtype of medulloblastoma (p=<0.01). Of 11 focal LEF1 positive cases, 4 were WNT-activated (all having classic histology and CTNNB1 mutation) and 7 were SHH-activated, TP53-wildtype (classic: 2 and desmoplastic nodular [D/N]: 5). None of the WNT-activated, 12 SHH-activated, TP53-wildtype (6 classic, 6 D/N), 1 SHH-activated, TP53-mutant (large-cell/Anaplastic [LC/A]) and all (n=28) non-WNT/non-SHH (classic: 25, LC/A: 3) were LEF1 negative. CONCLUSION Classic histology with diffuse (≥50% tumor cells; including heterogeneous intensity) LEF1 immunostaining is a good predictive marker for the WNT-activated molecular group of medulloblastoma, however focal staining is not.