engleski

Analysis of c-KIT expression in nonseminomatous testicular germ cell tumors

Incidence of testicular germ cell tumors (TGCT) has been continuously rising (1- 5% per year). (In Croatia the incidence of TGCT is increasing at the highest rate in the world. Croatia also has a high rate of mortality compared to other countries. Germ cell neoplasia in situ (GCNIS) is a precursor lesion of TGCT’s which makes up to 95% of all testicular tumors. TGCT are divided into pure seminomatous and non-seminomatous tumors. GCNIS is considered to be driven by an interplay of genetic, epigenetic and micro-environmental factors that lead up to an arrest of gonocyte differentiation. GCNIS is reprogrammed in the development of non- seminomas into embryonal carcinoma (EC) cells, which make up the pluripotent core of the non- seminomas. Currently used biomarkers for testicular cancer lack both specificity and sensitivity, and are used primarily as accessories in diagnostics. A deeper look into the molecular signature of nonseminomatous tumors is needed, due to their often times aggressive progression and cisplatin resistance. The aim of this study is the analysis of protein expression in nonseminomatous tissue as a potential biomarker of nonseminoma development and progression. Formalin-fixed paraffin-embedded tissue from 43 nonseminomatous testicular tumors from the Ljudevit Jurak Pathology and Cytology Department Archive, from the University Clinical Hospital Centre Sestre Milosrdnice, were used for immunohistochemical detection of c-KIT. Slides were analyzed semi- quantitatively, at the area of strongest reaction, by pathologist, on a scale from 0-3, depending on the percentage of reactive cells. The data was analyzed in GraphPad Prism using the Mann-Whitney test. The results have shown c-KIT staining in non-seminoma tissue to be comparable to healthy testis tissue. The intensity and positivity of c-KIT staining in non-seminoma is either fully absent, or if a “weak” signal is present it is mostly in the teratoma component. Germ cell neoplasia in situ (GCNIS) is c-KIT positive. The difference in c-KIT protein expression between GCNIS and teratoma versus other non-seminoma and healthy testis tissue opens a question on the role of c-KIT in non-seminoma development and differentiation.

c-KIT ; non seminoma ; analysis

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