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2.
Pathologe ; 37(2): 166-71, 2016 Mar.
Article in German | MEDLINE | ID: mdl-26942729

ABSTRACT

Nephroblastomas are the most commonly occurring renal neoplasms in childhood and are treated almost exclusively in clinical trials. An important factor for further therapeutic management is the pathological evaluation of the nephrectomy specimen. Tumor stage and risk group classification are the most crucial parameters. An independent assessment of the tumor by a reference pathology center is an essential standard procedure. Although many molecular genetic discoveries have been made in nephroblastomas over recent years, molecular parameters do not (yet) play a role in treatment stratification.


Subject(s)
Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Wilms Tumor/pathology , Wilms Tumor/therapy , Child , Clinical Trials as Topic , Guideline Adherence , Humans , Kidney/pathology , Kidney Neoplasms/genetics , Neoplasm Staging , Nephrectomy , Risk Assessment , Wilms Tumor/genetics
3.
QJM ; 109(6): 417-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26740505
4.
Oncogene ; 35(16): 2020-30, 2016 Apr 21.
Article in English | MEDLINE | ID: mdl-26189795

ABSTRACT

Current treatment regimens for rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer, rely on conventional chemotherapy, and although they show clinical benefit, there is a significant risk of adverse side effects and secondary tumors later in life. Therefore, identifying and targeting sub-populations with higher tumorigenic potential and self-renewing capacity would offer improved patient management strategies. Hedgehog signaling has been linked to the development of embryonal RMS (ERMS) through mouse genetics and rare human syndromes. However, activating mutations in this pathway in sporadic RMS are rare and therefore the contribution of hedgehog signaling to oncogenesis remains unclear. Here, we show by genetic loss- and gain-of-function experiments and the use of clinically relevant small molecule modulators that hedgehog signaling is important for controlling self-renewal of a subpopulation of RMS cells in vitro and tumor initiation in vivo. In addition, hedgehog activity altered chemoresistance, motility and differentiation status. The core stem cell gene NANOG was determined to be important for ERMS self-renewal, possibly acting downstream of hedgehog signaling. Crucially, evaluating the presence of a subpopulation of tumor-propagating cells in patient biopsies identified by GLI1 and NANOG expression had prognostic significance. Hence, this work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers.


Subject(s)
Carcinogenesis , Hedgehog Proteins/metabolism , Rhabdomyosarcoma, Embryonal/pathology , Signal Transduction , Humans , Prognosis , Rhabdomyosarcoma, Embryonal/metabolism , Tumor Cells, Cultured
5.
Br J Cancer ; 113(3): 411-3, 2015 Jul 28.
Article in English | MEDLINE | ID: mdl-26171934

ABSTRACT

BACKGROUND: Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies. METHODS: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue. RESULTS: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells. CONCLUSIONS: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.


Subject(s)
B7-H1 Antigen/metabolism , Neoplasms, Germ Cell and Embryonal/epidemiology , Neoplasms, Germ Cell and Embryonal/metabolism , Testicular Neoplasms/epidemiology , Testicular Neoplasms/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/pathology , Seminoma/epidemiology , Seminoma/metabolism , Seminoma/pathology , Testicular Neoplasms/pathology , Testis/metabolism , Testis/pathology , Tissue Array Analysis , Young Adult
6.
Pathologe ; 35(3): 224-31, 2014 May.
Article in German | MEDLINE | ID: mdl-24744185

ABSTRACT

Testicular germ cell tumors are generally rare but represent the most common solid neoplasms in young men. They are subdivided into seminomas and non-seminomatous germ cell tumors. Usually the diagnosis of a seminoma is straightforward due to the characteristic morphology, although problems in differential diagnosis can occur because of unusual histological growth patterns. This article describes the challenging differential diagnosis with respect to seminomas versus non-seminomatous germ cell tumors, sex cord stromal tumors, lymphomas and non-neoplastic conditions, such as scars and inflammatory changes. In addition, prognostic factors for seminomas are presented and discussed.


Subject(s)
Seminoma/pathology , Testicular Neoplasms/pathology , Choriocarcinoma/pathology , Diagnosis, Differential , Endodermal Sinus Tumor/pathology , Humans , Lymphoma/pathology , Male , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Sertoli Cell Tumor/pathology , Sex Cord-Gonadal Stromal Tumors/pathology , Testicular Diseases/pathology , Testis/pathology
7.
Pathologe ; 30(6): 478-80, 2009 Nov.
Article in German | MEDLINE | ID: mdl-19784652

ABSTRACT

Sialolipoma is a relatively new and rare variant of lipoma of the salivary glands characterized by the combination of classical lipoma morphology with non-neoplastic ductulo-acinary salivary tissue components. Including the presented case, 27 sialolipomas, 14 of them localized in the parotid gland, have been published. We describe the clinical, radiological and pathomorphological characteristics of a parotid sialolipoma in a 43-year-old man.


Subject(s)
Lipoma/diagnosis , Lipoma/pathology , Parotid Neoplasms/diagnosis , Parotid Neoplasms/pathology , Adult , Diagnosis, Differential , Humans , Lipoma/surgery , Magnetic Resonance Imaging , Male , Parotid Gland/pathology , Parotid Gland/surgery , Parotid Neoplasms/surgery
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