Prognostic Impact of Notch1 Intracellular Domain, P63, and c-MYC in Lacrimal Gland Adenoid Cystic Carcinoma

Authors

Jiawei Zhao
Michelle D Williams
Mike Hernandez
Grace Kuang
Hila Goldberg
Janet Fan
Jing Ning
Renata Ferrarotto
Bita Esmaeli

Publication Date

9-3-2024

Journal

Investigative Ophthalmology & Visual Science

Abstract

PURPOSE: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC).

METHODS: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC.

RESULTS: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none had nodal or distant metastasis at diagnosis. Tumors were positive for NICD1 expression in eight cases (38%), c-MYC expression in eight (38%), and P63 expression in 11 (52%). Positive NICD1 expression was associated with predominantly solid (vs. cribriform/tubular) pattern (P < 0.001), treatment with orbital exenteration (vs. eye-sparing surgery) (P = 0.008), local recurrence (P = 0.047), and death (P = 0.012). Negative P63 expression was associated with predominantly solid pattern (P = 0.001), local recurrence (P = 0.012), distant metastasis (P = 0.001), and death (P = 0.035). A higher percentage of tumor cells staining for c-MYC was associated with presence of perineural invasion (P = 0.036). Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26).

CONCLUSIONS: IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Keywords

Humans, Carcinoma, Adenoid Cystic, Male, Middle Aged, Female, Adult, Prognosis, Lacrimal Apparatus Diseases, Aged, Proto-Oncogene Proteins c-myc, Eye Neoplasms, Retrospective Studies, Biomarkers, Tumor, Receptor, Notch1, Immunohistochemistry, Young Adult, Membrane Proteins, Transcription Factors, Tumor Suppressor Proteins, lacrimal gland adenoid cystic carcinoma, Notch1 intracellular domain, P63, c-MYC

Comments

PMID: 39230995