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. 2023 Feb 16;23(1):161.
doi: 10.1186/s12885-023-10619-6.

The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma

Huiyang Li  1 , Bo Ren  1 , Shili Yu  1 , Hongwen Gao  1 , Ping-Li Sun  2
Affiliations

The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma

Huiyang Li et al. BMC Cancer. .

Abstract

Background: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit β5t (β5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4.

Methods: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis.

Results: Our results found that for cortical epithelial markers the expression of β5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of β5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and β5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival.

Conclusion: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including β5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.

Keywords: Cortex; Differentiation; Immunohistochemical staining; Medulla; Thymic epithelial markers; Thymic squamous cell carcinoma; Thymoma.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Expression of cortical epithelial markers in thymoma and TSCC. (a) β5t in AB thymoma × 400; (b) β5t in A thymoma × 200; (c) PRSS16 in B1 thymoma × 200; (d) PRSS16 in B2 thymoma × 200; (e) Cathepsin V in AB thymoma × 200; (f) Cathepsin V in B1 thymoma × 100
Fig. 2
Fig. 2
Expression of medullary epithelial markers in thymoma and TSCC. (a) CD40 in AB thymoma × 200; (b) CD40 in B1 thymoma × 100; (c) Claudin-4 in AB thymoma × 200; (d) Claudin-4 in B1 thymoma × 100; (e) AIRE in A thymoma × 400; (f) AIRE in AB thymoma × 400
Fig. 3
Fig. 3
Associations between histological classification and CD40 and AIRE expression
Fig. 4
Fig. 4
Comparison of corticomedullary epithelial immunophenotype in thymomas and TSCC
Fig. 5
Fig. 5
Kaplan-Meier curves of cathepsin V expression and PFS in thymomas and TSCC
See this image and copyright information in PMC

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