Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma

Mizuki Tagami; Hiroaki Kasashima; Anna Kakehashi; Atsuko Yoshikawa; Mizuho Nishio; Norihiko Misawa; Atsushi Sakai; Hideki Wanibuchi; Masakazu Yashiro; Atsushi Azumi; Shigeru Honda

doi:10.3389/fonc.2024.1277749

Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma

Front Oncol. 2024 Jan 23:14:1277749. doi: 10.3389/fonc.2024.1277749. eCollection 2024.

Authors

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
² Ophthalmology Department and Eye Center, Kobe Kaisei Hospital, Kobe, Japan.
³ Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
⁴ Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
⁵ Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan.

Abstract

Purpose: To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma.

Methods: Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images.

Results: GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01).

Conclusion: GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.

Keywords: RNA sequencing; artificial segmentation image; epithelial-mesenchymal transition; extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type; ocular adnexa MALT lymphoma; tumor stroma; vimentin.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by JSPS KAKENHI Grant Numbers 23K09013, the Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical’s Founder, and 2023 Osaka Community Foundation (MT).