Expression of Programmed Cell Death-L1 (PD-L1) Protein and Mismatch Repair Mutations in Orbital Tumours-a Pilot Study.

AlSemari, Mohammad A; Strianese, Diego; Abu Safieh, Leen; Al Hussain, Hailah; Abedalthagafi, Malak; Edward, Deepak P

AlSemari, Mohammad A; Strianese, Diego; Abu Safieh, Leen; Al Hussain, Hailah; Abedalthagafi, Malak; Edward, Deepak P.

Afiliación

AlSemari MA; 46670King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Strianese D; 46670King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Abu Safieh L; Department of Neuroscience, University of Naples Federico II School of Medicine and Surgery, Italy.
Al Hussain H; Genomic Research Department, 37849King Fahad Medical City, Riyadh, Saudi Arabia.
Abedalthagafi M; Saudi Human Genome Project, 83527King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Edward DP; 46670King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

Eur J Ophthalmol ; 32(5): 3097-3102, 2022 Sep.

Article en En | MEDLINE | ID: mdl-34931541

RESUMEN

PURPOSE: Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment.Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours. METHODS: We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2, MLH1, MSH6 and MSH2. RESULTS: The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6. CONCLUSIONS: Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour.

Asunto(s)

Neoplasias Orbitales; Rabdomiosarcoma; Apoptosis; Proteínas Reguladoras de la Apoptosis/genética; Antígeno B7-H1/genética; Antígeno B7-H1/metabolismo; Biomarcadores de Tumor/genética; Biomarcadores de Tumor/metabolismo; Neoplasias Encefálicas; Neoplasias Colorrectales; Reparación de la Incompatibilidad de ADN/genética; Proteínas de Unión al ADN/genética; Proteínas de Unión al ADN/metabolismo; Humanos; Mutación; Síndromes Neoplásicos Hereditarios; Neoplasias Orbitales/genética; Proyectos Piloto; Receptor de Muerte Celular Programada 1/genética; Rabdomiosarcoma/genética

Palabras clave

Mismatch repair (MMR); Programmed cell death ligand 1 (PD-L1) protein; lacrimal gland tumours; orbital tumours; rhabdomyosarcoma

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Rabdomiosarcoma / Neoplasias Orbitales Límite: Humans Idioma: En Revista: Eur J Ophthalmol Asunto de la revista: OFTALMOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Estados Unidos

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