CALML5 is a novel diagnostic marker for differentiating thymic squamous cell carcinoma from type B3 thymoma

CALML5 是区分胸腺鳞状细胞癌和 B3 型胸腺瘤的新型诊断标记物

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作者:Koichiro Kanamori, Kentaro Suina, Takehito Shukuya, Fumiyuki Takahashi, Takuo Hayashi, Kieko Hara, Tsuyoshi Saito, Yoichiro Mitsuishi, Shoko Sonobe Shimamura, Wira Winardi, Ken Tajima, Ryo Ko, Tomoyasu Mimori, Tetsuhiko Asao, Masayoshi Itoh, Hideya Kawaji, Yoshiyuki Suehara, Kazuya Takamochi, Kenji

Background

Thymic squamous cell carcinoma and type B3 thymoma are primary neoplasms of the anterior mediastinum that are sometimes difficult to differentiate from one another histologically. However, only a few immunohistochemical markers are available for the differential diagnosis. The

Conclusion

We identified CALML5 as a potential marker for differentiating thymic squamous cell carcinoma from type B3 thymoma. It is assumed that future clinical use of CALML5 may improve the diagnostic accuracy of differentiating between these two diseases.

Methods

We used histological samples of thymic carcinomas (n = 26) and type B3 thymomas (n = 38) which were resected between 1986 and 2017. To search for candidates of differential markers, gene expression levels were evaluated in samples using promoter analysis by cap analysis of gene expression (CAGE) sequencing.

Results

Promoter level expression of CALML5 genes was significantly higher in thymic carcinomas than in type B3 thymomas. We further validated the results of the CAGE analysis in all 26 thymic carcinomas and 38 type B3 thymomas by immunohistochemistry (IHC). CALML5 was strongly expressed in the cytoplasm in 19 of 26 cases with thymic carcinoma, whereas positivity at the protein level was shown in two of 38 type B3 thymomas. Thus, the sensitivity (73.1%) and specificity (94.7%) of CALML5 as markers for immunohistochemical diagnosis of thymic carcinoma were extremely high.

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