Objective Several studies analyzed the “reprogramming” of germ cell tumors of the testis (GCTT), known to be an epigenetic process that results in the preservation of stem cell features and/or differentiation of GCTT. EZH2 is a methyltransferase involved in the epigenetic regulation of tumors and has become a promising therapeutic target, but few studies have analyzed its expression in GCTT, germ cell neoplasia in situ (GCNIS), and adjacent testis. Methods We tested 131, 36, and 29 GCTT components, GCNIS, and adjacent testes, respectively. EZH2 expression was evaluated by H-score and compared between different subgroups by adopting median values and the Fisher exact test. Results We found that EZH2 was more highly expressed by adjacent testis/GCNIS rather than by GCTT (P < .001), with adjacent testis showing the highest values and being statistically significant compared to GCNIS (P < .001). In adjacent testis, EZH2 expression was mainly detected in spermatocytes (primary and secondary) and spermatids, with scattered positive spermatogonia. Seminoma/embryonal carcinoma showed statistically significantly higher EZH2 expression compared to the other nonseminomatous GCTT (P = .027). Conclusions EZH2 is differentially expressed during GCTT reprogramming (adjacent testis [very high levels] → GCNIS [high levels] → seminoma/embryonal carcinoma [moderate levels] → other nonseminomatous GCTT [low/absent levels]), supporting its involvement in the epigenetic regulation for determining the fate of GCTT.
Immunohistochemical expression of EZH2 in germ cell tumors of the testis: New insights into the genesis and epigenetic reprogramming of these fascinating tumors / Melotti, S., Ambrosi, F., Franceschini, T., Giunchi, F., Vasuri, F., Orsatti, A., Di Sciascio, L., Grillini, A., Franchini, E., Massari, F., Mollica, V., Marchetti, A., Mineo Bianchi, F., Colecchia, M., Acosta, A.M., Lobo, J., Fiorentino, M., Ricci, C.. - In: AMERICAN JOURNAL OF CLINICAL PATHOLOGY. - ISSN 0002-9173. - 164:5(2025), pp. 739-745. [10.1093/ajcp/aqaf098]
Immunohistochemical expression of EZH2 in germ cell tumors of the testis: New insights into the genesis and epigenetic reprogramming of these fascinating tumors
Colecchia M.;
2025-01-01
Abstract
Objective Several studies analyzed the “reprogramming” of germ cell tumors of the testis (GCTT), known to be an epigenetic process that results in the preservation of stem cell features and/or differentiation of GCTT. EZH2 is a methyltransferase involved in the epigenetic regulation of tumors and has become a promising therapeutic target, but few studies have analyzed its expression in GCTT, germ cell neoplasia in situ (GCNIS), and adjacent testis. Methods We tested 131, 36, and 29 GCTT components, GCNIS, and adjacent testes, respectively. EZH2 expression was evaluated by H-score and compared between different subgroups by adopting median values and the Fisher exact test. Results We found that EZH2 was more highly expressed by adjacent testis/GCNIS rather than by GCTT (P < .001), with adjacent testis showing the highest values and being statistically significant compared to GCNIS (P < .001). In adjacent testis, EZH2 expression was mainly detected in spermatocytes (primary and secondary) and spermatids, with scattered positive spermatogonia. Seminoma/embryonal carcinoma showed statistically significantly higher EZH2 expression compared to the other nonseminomatous GCTT (P = .027). Conclusions EZH2 is differentially expressed during GCTT reprogramming (adjacent testis [very high levels] → GCNIS [high levels] → seminoma/embryonal carcinoma [moderate levels] → other nonseminomatous GCTT [low/absent levels]), supporting its involvement in the epigenetic regulation for determining the fate of GCTT.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
