Germ cell tumors in children and adolescents in Finland: trends over 1969-2008.

PURPOSE: Malignant germ cell tumors (GCTs) are a heterogeneous group of neoplasms putatively originating from the primordial germ cell. In adults, an increasing incidence of GCTs, particularly testicular tumors, has been reported in recent decades. However, population-based evidence in children and adolescents remains limited. We investigated the incidence of malignant GCTs diagnosed in childhood or adolescence, using population-based nationwide data from Finland. METHODS: We obtained information from the Finnish Cancer Registry on all malignant GCTs registered in 1969-2008 in children or adolescents aged 0-19 years. Data on tumor location, histology, stage, and survival were collected. Age-standardized incidence and survival rates were calculated. RESULTS: A total of 334 cases of malignant GCT were identified. Their proportion among all malignant tumors among 0- to 19-year-olds increased from 3 to 9.7% in boys with time, but remained stable in girls (3%). The overall incidence rate was 0.6 per 100,000 (0.8 in boys and 0.4 in girls), and differed significantly between the age groups. A significant increase in the incidence of testicular GCTs was seen in boys in the age group of 15-19 years. CONCLUSIONS: 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.

High prevalence of sacrococcygeal teratoma in Finland - a nationwide population-based study.

AIM: The birth prevalence of sacrococcygeal teratoma (SCT) has been reported to range from 1:27 000 to 1:40 000. We assessed the population-based prevalence and clinical presentation of SCT over 22 years. METHODS: We identified all cases of SCT, including live births, stillbirths and terminations of pregnancy (TOPs), in the Finnish Register of Congenital Malformations, covering 1987-2008. Data on prenatal diagnoses, pregnancy outcomes, infant deaths and associated anomalies were collected. RESULTS: One hundred and twenty four SCT cases were identified among 1 331 699 pregnancies. There were 89 (72%) live births, 13 (10%) stillbirths and 22 (18%) TOPs. The total prevalence of SCT was 1:10 700. Tumours were detected in utero in 55% of the pregnancies with SCT. The proportion of perinatal deaths among all SCT births was 28%. Thirty percentage of the cases had associated abnormalities (mainly of the urinary tract and various syndromes). CONCLUSION: 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 incidences of malignant gonadal and extragonadal germ cell tumors in males and females: a population-based study covering over 40 years in Finland.

PURPOSE: Germ cell tumors (GCTs) comprise a heterogeneous group of tumors derived from primordial germ cells. The incidence of malignant testicular GCTs has increased in recent decades, but little is known about possible changes in malignant female GCTs. Population-based data covering all malignant GCTs in both sexes remain limited. METHODS: All cases of malignant GCTs in 1969-2008 were collected from the Finnish Cancer Registry and their age-adjusted annual incidences calculated. RESULTS: The overall incidence of malignant GCTs was 2.56 per 100,000 person-years in males and 0.34 per 100,000 in females. The incidence of gonadal GCTs increased from 2.27 to 8.36 per 100,000 in males between 15 and 44 years of age. Moreover, the incidence of all histological subtypes of gonadal GCTs increased in males. In females, the only increase was seen in the incidence of ovarian non-dysgerminoma (from 0.07 to 0.29/100,000). The incidence of extragonadal GCTs did not change during the study period, being 0.18 and 0.10 per 100,000 in males and females, respectively. CONCLUSIONS: 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.

Influence of text cohesion on the persuasive power of expository text.

The present study examined how global text cohesion affects persuasion and memory for message arguments presented in expository text. Sixty-nine participants who held a neutral prior attitude towards NATO read a persuasive text about NATO that was either high or low in global cohesion. After reading, participants voted whether Finland should seek NATO membership and filled in an attitude questionnaire. After a 1-week delay they returned for a surprise recall task. The results showed that the high cohesion text was more persuasive than the low cohesion text. Moreover, attitude after reading but not text cohesion predicted later recall of the message arguments. The results show that global text cohesion increases text's persuasive power and that readers who form a positive attitude have better memory of the persuasive arguments after a delay than readers who are less persuaded.

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors.

OBJECTIVE: Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive 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-Müllerian hormone/Müllerian-inhibiting substance (AMH), and inhibin-alpha (INHalpha). 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 INHalpha 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.

Oestrogen receptors and small nuclear ring finger protein 4 (RNF4) in malignant ovarian germ cell tumours.

The peak incidence of malignant ovarian germ cell tumours occurs soon after puberty. Thus, gonadal steroids may play a role in their development. Oestrogen receptors (ERalpha and ERbeta) and their co-regulators, including small nuclear ring finger protein 4 (SNURF/RNF4) mediate oestrogen actions. While ERbeta and SNURF are down-regulated in testicular germ cell tumours, their role in the ovarian germ cell tumours remains unknown. We herein studied the different subtypes of malignant ovarian germ cell tumours, and found that they all express ERalpha, ERbeta, and SNURF. Stimulation with oestradiol (E2), ERalpha, ERbeta and SNURF significantly up-regulated mRNA expression in the human germinoma derived NCC-IT cells. Further, the effects of E2 were counteracted by an anti-oestrogen (ICI 182,780). Neither E2 nor ICI 182,780 had an effect on the proliferation of NCC-IT cells as assessed by flow cytometric analysis. Our results suggest that oestrogen signalling has a role in malignant ovarian germ cell tumours.

Tissue AP-2gamma and Oct-3/4, and serum CA 125 as diagnostic and prognostic markers of malignant ovarian germ cell tumors.

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 alpha-fetoprotein, human chorionic gonadotropin and CA 125 were determined, and immunohistochemistry for CA 125 as well as the pluripotent stem cell markers AP-2gamma 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-2gamma 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-2gamma and Oct-3/4 are associated with dysgerminomas and can thus be used as additional differential diagnostic tools in MOGCTs.

Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors.

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.