engleski

TGCT expression profiling, the road to better diagnostics

Testicular germ cell tumors (TGCT) incidence has been continuously rising across the world. Croatia is no exception, with the highest rise in incidence accompanied by a higher rate of mortality compared to other countries. TGCT's make up 95% of testicular tumors and are classified as pure seminoms (SE) and non—seminomas (NS), both considered to originate from germ cell neoplasia in situ (GCNIS) as a precursor lesion. GCNIS is considered to be driven by an interplay of genetic, epigenetic and micro— environmental factors leading up to an arrest of gonocyte differentiation. Currently used biomarkers for TGCT lack specificity and sensitivity and are used as accessories in diagnostics, making hematoxylineosin stain the dominant diagnostic method. Due to the heterogenous nature of TGCT more robust biomarkers are needed for early diagnostics and diagnostic certainty. For immunohistochemical detection of HOXA9, MGMT and cKIT, 108 formalinfixed paraffin-embedded TGCT's from KBC SM and KBC ZAG and 9 non-tumorous testes were used. Slides were analyzed semi— quantitatively by pathologists quantifyingexpression percentage (0-5) and expression intensity (0-3) resulting in an immunoractive score (IRS 0-15). IRS 53 was then classified as diagnostically negative and IRS 24 as diagnostically positive. The data was analyzed in GraphPad Prism using the Mann-Whitney test and Kruskal- Wallis with Dunn's multiple test correction. The difference in protein expression of the investigated genes allows for differentiation between healthy testis vs. TGCT and GCNIS, and further discrimination between TGCT and GCNIS, as well as SE vs. NS. With better understanding of TGCT and GCNIS tumorigenesis, more precise diagnostics of heterogenous TGCT components is provided.

TGCT ; gene expression profiling ; diagnostics

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