News in the fifth edition of World Health Organization classification of testicular tumors.

BACKGROUND: The fifth edition of World Health Organization classification of urinary and male genital tumours also brought news regarding testicular tumours. In contrast to the previous editions' radical alterations, the adjustments in the fifth edition are subtle and mostly impact the terminology, categorization of some of the rare tumours and diagnostic criteria. PURPOSE: Acquainting with current terms and tumor classification, which is necessary for good clinical practice.

A novel fetal sequence patogenesis resulting in oral meningoencephalocele.

OBJECTIVES: To analyze a rare triad of intracranial fetal pathologies and clinical study of the novel defined sequence pathogenesis based on prenatal and postmortem findings. METHODS: Complex multidisciplinary clinical analysis and review of up-to-date literature. RESULTS: In an 18-gestational-week fetus the screening ultrasound scan resembled the semilobar type of holoprosencephaly and oral tumor. After the indicated termination of pregnancy, the histopathology results confirmed another pathologies - oral meningoencephalocele, teratoma of the sellar area and large arachnoidal cyst of the anterior cerebral fossa. The surprising final results were evaluated by specialists in prenatal diagnosis, histopathology, genetics, neurology, and radiology. CONCLUSION: We defined the final diagnosed triad oral meningoencephalocele - intracranial sellar teratoma- arachnoidal cyst as a novel sequence defect malformation. In the detailed sequence pathogenesis, the intracranial sellar teratoma created an aperture for meningoencephalocele in the cranial base and the arachnoidal cyst facilitated, by its growth and pressure, the protrusion of the brain tissues (Fig. 4, Ref. 10). Text in PDF www.elis.sk.

Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ.

BACKGROUND: Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Fibrillins, which are integral components of microfibrils are suggested to be involved in cancer pathogenesis and maintenance of embryonic stem cells pluripotency. The aim of this study was to examine fibrillin-1 (FBN-1) expression in TGCTs patients. METHODS: Surgical specimens from 203 patients with TGCTs were included into the translational study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in adjacent non-neoplastic testicular tissue in all available cases. Tissue samples were processed by the tissue microarray method. FBN-1 was detected by immunohistochemistry using goat polyclonal antibody and the expression was evaluated by the multiplicative quickscore (QS). RESULTS: The highest FBN-1 positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1 (QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of TGCTs was significantly lower in comparison to expression in GCNIS (all p <0.001). Seminoma had significantly higher expression compared to EC, ChC and TER (all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity, positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS were 97.1, 98.8, 98.6 and 97.7 %. CONCLUSIONS: FBN-1 is overexpressed in TGCTs and especially in GCNIS when compared to non-neoplastic testicular tissue in patients with germ cell tumors and could be involved in germ cell neoplasia in situ development.

CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer.

BACKGROUND: Cytokines are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play key role in tumor dissemination and are an independent survival predictor in breast cancer patients. The aim of this study was to assess correlation between CTCs and plasma cytokines in primary breast cancer (PBC) patients. METHODS: This study included 147 chemotherapy naïve PBC patients. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoetic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (Twist1, Snail1, Slug, Zeb1) and epithelial (Ck19) gene transcripts by qRT-PCR. The concentrations of 51 plasma cytokines were measured using multiplex bead arrays. RESULTS: CTCs were detected in 25.2% patients. CTCs exhibiting only epithelial markers (CTC_EP) and only EMT markers (CTC_EMT) were present evenly in 11.6% patients, while CTCs co-expressing both markers were detected in 2.0% patients. Patients with presence of CTC_EP in peripheral blood had significantly elevated levels of plasma IFN-α2, IL-3, MCP-3, ß-NGF, SCF, SCGF-ß, TNF-ß and SDF-1 compared to patients without CTC_EP. CTC_EP exhibited overexpression of SDF-1 receptor and CXCR4, but not other corresponding cytokine receptor, and in multivariate analysis SDF-1 was independently associated with CTC_EP. There was an inverse correlation between CTC_EMT and plasma cytokines CTACK, ß-NGF and TRAIL, while presence of either subtype of CTCs was associated with increased level of TGF-ß2. CONCLUSION: Using cytokine profiling, we identified cytokines associated with CTCs subpopulations in peripheral blood of PBC. Our data suggest that CXCR4-SDF-1 axis is involved in mobilization and trafficking of epithelial CTCs.

Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs. PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome. RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression. CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.

Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer.

BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. METHODS: This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. RESULTS: CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. CONCLUSIONS: In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features.

[Expression of p57 marker in differential diagnosis of complete and partial mole - correlation with DNA analysis]. / Expresia markeru p57 v diferenciálnej diagnostike kompletnej a parciálnej moly - korelácia s DNA analýzou.

Nowadays valid classification of gestational trophoblastic disease, according to the World Health Organisation from the year 2003, divides gestational trophoblastic disease into three groups - molar pregnancies, non-neoplastic non-molar changes of trophoblast and tumours of trophoblast. To the molar pregnancies belong complete, partial, invasive and metastatic hydatidiform mole. In the differential diagnosis it is important to distinguish the complete hydatidiform mole from other forms of gestational trophoblastic disease, because there is an increased risk of malignant transformation of trophoblast cells in complete hydatidiform mole. 10 cases of genetically confirmed diploid complete mole and 10 cases of genetically confirmed triploid partial mole were included into our retrospective study. All cases were examined microscopically in the basic haematoxillin and eosin staining and immunohistochemically with the use of antibodies against human choriogonadotropin hormone, placental alkaline phosfatase and protein p57. Villous cytotrophoblast, stromal villous cells, extravillous trophoblast and decidual cells were p57 positive in all cases of partial hydatidiform mole. All 10 cases of complete hydatidiform mole were p57 negative in stromal villous cells and villous cytotrophoblast. P57 protein is a marker distinguishing complete hydatidiform moles from partial moles.