DNA methylation profiling as a tool for testicular germ cell tumors subtyping.

AIM: Assess differential patterns of selected five genes' promoter methylation among testicular germ cell tumors (TGCT) subtypes. MATERIALS & METHODS:  CRIPTO, HOXA9, MGMT, RASSF1A and SCGB3A1 promoter methylation levels were evaluated by quantitative methylation-specific PCR in 161 TGCT and 16 controls. Associations between clinicopathological parameters and promoter methylation levels were assessed, and receiver operating characteristics curve analysis was performed. RESULTS: Promoter methylation of CRIPTO/HOXA9/SCGB3A1 panel and RASSF1A best discriminated between controls and nonseminomatous tumors or seminomas, respectively, whereas HOXA9/RASSF1A panel displayed the best discriminative performance between nonseminomatous tumor and seminomas. Significant differences in CRIPTO, MGMT and RASSF1A methylation levels were depicted between pure forms and matched mixed components of seminomas and embryonal carcinoma. HOXA9, RASSF1A and SCGB3A1 promoter methylation significantly associated with tumor stage. CONCLUSION: Different combinations of five genes' promoter methylation levels discriminate among TGCT subtypes. Methylation patterns may also assist in identification of more clinically aggressive tumors.

Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists.

Testicular germ cell tumors (TGCTs) are strikingly heterogeneous, reflecting a complex tumor model, posing serious challenges for pathologists. Accurate classification and staging, according to most recent systems, is fundamental. We aimed to revise a series of consecutively diagnosed TGCTs (2005-2016) in light of the new World Health Organization (WHO) classification and American Joint Committee on Cancer (AJCC) staging systems, discussing dilemmas imposed to pathologists. All 164 patients' clinical files/histological slides were reviewed. Follow-up was last updated on November 2017. Statistical analysis was performed with SPSS (v24). P < 0.05 was considered significant. Non-seminomatous tumors (NSTs) showed more frequently cysts, necrosis, hemorrhage, lymphovascular invasion (LVI) and higher stage than seminomas (SEs) (P < .001, P = .015, P < .001, P = .001, P = .007). Embryonal carcinoma (EC), yolk sac tumor (YST) and teratoma (TE) were the most frequent components in mixed tumors (82.5%, 82.5% and 80.7%). SEs with "atypical features" showed more LVI, higher mitotic count and more extensive necrosis (P = .030, P < .001, P = .016). LVI and >50%EC component, but not rete testis invasion, were associated with higher stage (P < .001, P = .009). Regarding SEs, there was an association between tumor size and both stage (P = .004) and LVI (P < .001). Only four patients disclosed altered stage group when AJCC 8th Edition was employed. Disease recurrence/progression occurred in 5.4% of cases. In two cases, tumor components in metastasectomy specimens were not present in the primary TGCT. Overall survival at 5 years was 98.6%. TGCTs are challenging neoplasms, and pathologists and clinicians alike must be aware of recent updates in classification and staging for adequately tailoring treatment strategies.

Germ cell tumour subtypes display differential expression of microRNA371a-3p.

Testicular germ cell tumours (TGCTs) are a heterogeneous group of neoplasms, mostly affecting young men. Curability rates are high and adequate treatment relies on careful and accurate pathological and clinical assessment. Indeed, TGCTs' histopathological subtyping is critical for adequate therapeutic decision. Considering the limitation of currently available serum biomarkers, novel candidates have been proposed, most notably miR-371a-3p, which outperformed classical serum markers, but no detailed information concerning TGCT subtype was available. Thus, we carried out evaluation of miR-371a-3p expression levels among TGCT subtypes using a consecutive cohort of tissue samples. MiR-371a-3p discriminated TGCTs from control tissues with high sensitivity and specificity (AUC = 0.99). Furthermore, seminomas displayed higher miR-371a-3p expression levels compared to non-seminomatous TGCTs, which also showed significant differences among them. Nonetheless, prepubertal TGCTs depicted lower miR-371a-3p expression levels than postpubertal TGCTs. Globally, miR-371a-3p expression levels decreased in parallel with progressive cell differentiation. We concluded that miR-371a-3p is TGCTs-specific and it might be clinically useful for early detection and disease monitoring.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.