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In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the MET gene. This alteration can be due to de novo amplification of the MET gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.

Objective: This study sought to evaluate the clinical outcome after extended sentinel lymph node dissection (eSLND) and radical retropubic prostatectomy (RRP) in patients with clinically localized prostate cancer (PCa)., Subjects and Methods: From August 2002 until February 2011, a total of 819 patients with clinically localized PCa, confirmed by biopsy, were treated with RRP plus eSLND. Biochemical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed with Kaplan-Meier curves. Various histopathological parameters were analyzed by univariate and multivariate analysis., Results: The mean follow-up was 5.3 years. Lymph node (LN) metastases occurred in 140 patients. We removed an average of 10.9 LNs via eSLND from patients with pN1 PCa. Postoperatively, 121 pN1 patients temporarily received adjuvant androgen deprivation therapy. The mean survival periods for RFS, RFS after secondary treatment, CSS, and OS were 4.7, 7.0, 8.8, and 8.1 years, respectively. The cancer-specific death rate of the 140 pN1 patients was 13.6%. RFS, CSS, and OS were significantly correlated with pathological margin status, LN density, the total diameter of evident metastases, and membership in the subgroup 'micrometastases only'., Conclusion: Despite the presence of LN metastases, patients with a low nodal tumor burden demonstrate a remarkable clinical outcome after undergoing eSLND and RRP, thus suggesting a potential curative therapeutic approach., (2014 S. Karger AG, Basel)

Background: The Wnt and BMP signaling pathways are involved in the morphogenesis of both gastrointestinal and choroid plexus epithelium. In the intestine, Wnt signaling represses the expression of the tumor suppressor gene CDX2 via SOX9, a transcription factor, which is also expressed in the choroid plexus. Recently, an inverse correlation between CDX2 expression and tumor grade, tumor stage and lymph node metastasis in colorectal adenocarcinomas has been reported. Besides intestinal tissues, expression of CDX2 has also been reported in various other epithelial tissues and carcinomas. To date, no data exist on expression of CDX2 in normal and neoplastic choroid plexus epithelium., Aim: To investigate CDX2 expression in normal and neoplastic choroid plexus., Materials and Methods: Paraffin-embedded samples from 60 normal choroid plexus, including 23 fetal tissue samples and from 65 choroid plexus tumors (47 choroid plexus papillomas WHO grade I, 16 atypical choroid plexus papillomas and 2 choroid plexus carcinomas WHO grade III) were examined by immunohistochemistry. Samples from normal choroid plexus were collected from 45 autopsy cases and from 15 neurosurgical specimens., Results: Normal and neoplastic choroid plexus lacked CDX2 expression., Conclusion: In our series, immunohistochemistry shows no evidence for a role of CDX2 in development or differentiation of normal choroid plexus from the 9th gestational week until adulthood. Since choroid plexus tumors reliably lack CDX2 immunoreactivity, this marker may be helpful in distinguishing cerebral metastases from CDX2-positive adenocarcinomas and choroid plexus neoplasms.

Hereditary motor and sensory neuropathy (HMSN) with autosomal recessive inheritance represents a genetically heterogeneous group of disorders with variable clinical, pathologic and electrophysiologic manifestations. A new variant of autosomal recessive HMSN, clinically defined by sensorimotor polyneuropathy associated with deafness and mental retardation, has recently been described. We report on the first autopsy case with this type of HMSN: a girl of non-consanguineous parents with a presumably autosomal recessive type of motor and sensory neuropathy clinically associated with deafness, mental retardation, and epilepsy. The autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves corresponding to a lack of large neurons in dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of the cerebellum. Molecular genetic analyses in our case revealed neither genetic alterations in the survival motor neuron gene nor in the PMP-22 gene.