This nationwide, population-based study on SCT shows that the total and birth prevalence of SCT in Finland is markedly higher than previously reported. This may reflect true differences between populations, but may also be explained by accurate nationwide registration of SCTs. The high perinatal mortality rate has an impact on counselling of families and planning of deliveries.

The incidence of gonadal GCTs in males increased significantly during the 40-year study period, whereas in females, no such change was observed. There were significant gender differences regarding the distribution of histological subtypes and patients' ages. However, the incidence of extragonadal GCTs remained low in both sexes. The differences in the incidences of gonadal GCTs derived from the same population suggest that the risk factors of these malignancies differ between the two sexes.

Objective: Testicular germ cell cancer is the most common malignancy among young males. The preinvasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms. Methods: Fetal testis, testicular CIS, and overt tumor samples were analyzed by immunohistochemistry for GATA-4, GATA-6, FOG-2, steroidogenic factor 1 (NR5A1/SF1), anti-Mü llerian hormone/Mü llerianinhibiting substance (AMH), and inhibin-a (INHa). Results: GATA-4 was not expressed in normal germ cells, except for a subset of gonocytes at the 15th gestational week. The CIS cells expressed GATA-4 and GATA-6 heterogeneously, whereas most of the CIS cells expressed GATA-4 cofactor FOG-2. GATA target gene SF-1 was expressed heterogeneously in CIS cells, whereas INHa and AMH were mostly negative. Seminomas and yolk sac tumors were positive for GATA-4 and GATA-6, but mostly negative for FOG-2 and the GATA target genes. In contrast, pluripotent embryonal carcinomas and choriocarcinomas were GATA-4 and GATA-6 negative. Conclusions: Differential expression of the GATA-4 target genes suggested cell-specific functions of GATA-4 in the germ and somatic cells. The GATA-4 expression in early fetal gonocytes, CIS, and seminoma cells but the absence in more mature germ cells is consistent with the early fetal origin of CIS cells and suggests that GATA-4 is involved in early germ cell differentiation.

Ovarian germ cell tumors (GCTs) are histologically heterogeneous neoplasms originating from activated germ cells, the oocyte stem cells. These rare tumors often contain many different tissues mixed together, and malignant components are occasionally hidden within benign tissues thus complicating the diagnosis. The reasons for the variable differentiation of germ cells are still largely unknown. As transcription factors GATA-4 and GATA-6 as well as their downstream factors (e.g. HNF-4, BMP-2 and Ihh) are essential for normal yolk sac development, we studied their expression in 19 ovarian GCTs. Endodermal markers were expressed distinctively in different GCT types. The malignant endoderm in yolk sac tumors expressed all factors of endodermal development included in the study. Dysgerminomas, on the contrary, expressed only GATA-4 and, in a minority of cases, Ihh and BMP-2. The results suggest that GATA-4 and GATA-6 detected in the ovarian GCTs have retained their normal function. The fact that GATA-6 and HNF-4 are expressed exclusively in endodermal tissues indicates that these transcription factors play a role in the differentiation of germ cells towards the endodermal phenotype. Analysis of the nuclear transcription factors in tumor tissue could serve as a new informative diagnostic tool for ovarian GCTs.

Although malignant GCTs are rare, their relative frequency in children and adolescents has increased during recent decades, the change being mainly due to an increasing frequency of the testicular tumors among teenagers. The causes of the increase remain unknown, but environmental exposures are likely to be involved.

No abstract

Histology, clinical stage and treatment response are used to define the prognosis of malignant ovarian germ cell tumors (MOGCTs). However, additional biological tools to guide treatment in MOGCTs would be desirable. We evaluated the prognostic value of several serum and tissue markers in MOGCTs. Medical charts of 30 women were reviewed as regards preoperative and treatment-related factors, with a mean follow-up time of 92 months (range 2–205). Serum levels of α-fetoprotein, human chorionic gonadotropin and CA 125 were determined, and immunohistochemistry for CA 125 as well as the pluripotent stem cell markers AP-2γ and Oct-3/4 was performed in tumor specimens and the NCC-IT human germinoma cell line. Overall survival was 73%. Elevated preoperative levels of serum CA 125 were prognostic of progressive disease (p<0.05). Immunohistochemical evaluation revealed that in most cases the elevated CA 125 levels originated from the tumor tissue. Most dysgerminomas as well as the germinoma cell line were positive for AP-2γ and Oct-3/4, whereas the majority of yolk sac tumors and immature teratomas were negative. Taken together, increased preoperative serum CA 125 levels indicate poor prognosis of MOGCTs. Tissue AP-2γ and Oct-3/4 are associated with dysgerminomas and can thus be used as additional differential diagnostic tools in MOGCTs.

Multiple myeloma (MM) is one of the most prevalent hematologic cancers. Treatments of MM have been improved by availability of novel therapies but require regular hospital visits and intense patient follow-up. In this real-world study, patient characteristics, first four treatment lines (1L-4L), and associated outcomes and costs were assessed among adults treated for active MM during 2009-2016 at Kymenlaakso Central Hospital, Kymsote hospital district, Finland. In addition, patient burden and travel costs were determined for the patients treated during 2015-2016. Ninety-seven patients fulfilled the inclusion criteria. Data were retrospectively collected from hospital's database, medical charts, and from healthcare professionals. Treatment lines and responses were defined according to the general recommendations. The median age at diagnosis was 70.1 years. The median overall survival was 68 months. Proteasome inhibitors (PI) or immunomodulatory drugs (IM) were the most common regimen types while the utilisation of a more novel approach, the simultaneous use of PI and IM, was low across first four treatment lines. Overall response rate was 72-74% for 1L-2L and 50-56% for 3L-4L. Drug costs represented the greatest proportion of total healthcare costs and increased in the later treatment lines. Patients receiving infusion treatments had specialised health care visits twice as much the patients treated with oral treatments. Furthermore, travel costs related to infusion treatments were three to four times more compared to the respective costs for oral treatments. Increasing drug costs but poorer treatment outcomes in later treatment lines underline a need for more efficient and better tolerated treatment options. This study demonstrates that oral treatments may indeed reduce patient and hospital resource burden and thus, should be considered in future health economic evaluations in Finland.