Rearrangements of the ROS1 gene occur in 1-2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

• MeSH
• genová přestavba genetika   MeSH
• lidé MeSH
• nádory plic diagnóza   genetika   metabolismus   MeSH
• nemalobuněčný karcinom plic diagnóza   genetika   MeSH
• onkogeny genetika   MeSH
• protoonkogenní proteiny genetika   MeSH
• tyrosinkinasové receptory genetika   MeSH
• tyrosinkinasy genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We present a series of 23 cases of a distinctive, hitherto poorly recognized low-grade adenocarcinoma, with several histologic features reminiscent of papillary carcinoma of the thyroid, and which mostly but not exclusively occurs in the tongue. All the tumors were unencapsulated and were divided into lobules that were composed mainly of cribriform and solid growth patterns. Therefore, we propose the name "cribriform adenocarcinoma of minor salivary gland origin (CAMSG)." All the patients were adults with a mean age at diagnosis of 55.8 years (range, 25 to 85 y). Fourteen of the 23 tumors were localized in the tongue, 3 in the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, and 1 in the upper lip. Fifteen patients of 23 had synchronous metastases in the cervical lymph nodes at the time of diagnosis, bilateral in 3 cases. In 3 patients, the nodal metastasis was the first evidence of disease, later investigation revealing primary neoplasms in the base of tongue and tonsil, respectively. In addition, 1 patient developed a cervical lymph node metastasis 8 years after excision of a primary tumor of the tongue. Data on treatment and follow-up were available in 14 cases. The patients were treated by radical excision with clear margins (12 cases) or by simple excision (2 cases). Neck dissection was performed in 10 patients; 9 received radiotherapy, but none were treated by chemotherapy. Clinical follow-up ranged from 2 months to 13 years (mean, 6 y and 5 mo). Twelve patients are alive with no evidence of recurrent or metastatic disease after treatment, 1 patient died 2 years after surgery without evidence of tumor, and 1 patient is alive with recurrent tumor of the palate.

• MeSH
• adenokarcinom genetika   mortalita   patologie   radioterapie   sekundární   chirurgie   virologie   MeSH
• adjuvantní radioterapie MeSH
• biopsie MeSH
• časové faktory MeSH
• DNA virů izolace a purifikace   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• krční disekce MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• lymfatické metastázy MeSH
• malé slinné žlázy patologie   chirurgie   virologie   MeSH
• mutační analýza DNA MeSH
• nádory jazyka genetika   mortalita   patologie   radioterapie   chirurgie   virologie   MeSH
• nádory slinných žláz genetika   mortalita   patologie   radioterapie   chirurgie   virologie   MeSH
• Papillomaviridae genetika   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

High-grade transformation of acinic cell carcinoma (AciCC) (previously referred to as dedifferentiation) is a rare phenomenon characterized by histologic progression of low-grade AciCC to high-grade adenocarcinoma or undifferentiated carcinoma. We report 9 new cases with immunohistochemical analysis and examination of HER-2/neu and p53 genes to further define the profile of this tumor. Histologically, the high-grade component was composed of polymorphic cells with a high mitotic rate arranged in glandular and solid growth patterns with comedonecrosis. The MIB-1 labeling indices were elevated in the high-grade component, as compared with the low grade conventional AciCC. The high-grade component of AciCC was characterized by strong membrane staining for CK18 and beta-catenin, and nuclear staining for cyclin-D1. HER-2/neu, androgen receptor, C-kit, and epidermal growth factor receptor were absent from both low-grade and high-grade components. In contrast, S-100 protein, alpha-1-antitrypsin, and lysozyme were lost only in high-grade foci of transformed AciCC. The median age was 61 years (with range from 43 to 76 y). Lymph node (LN) metastases were found in 5 of 9 cases (56%). Distant metastases to the lungs (n=4), pleura (n=2), brain (n=3), and peritoneum (n=1), and paraaortic, paratracheal, and mediastinal LNs (n=2) were observed. Six of 9 patients (66%) died from tumor dissemination, all with a median overall survival of 4.3 years (range: 1 to 9 y). The high propensity for LN metastases indicates the need for neck dissection at the time of diagnosis.

• MeSH
• acinární karcinom genetika   metabolismus   patologie   MeSH
• dospělí MeSH
• geny erbB-2 MeSH
• geny p53 MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutační analýza DNA MeSH
• nádorová transformace buněk genetika   MeSH
• nádorové biomarkery analýza   MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• nádory příušní žlázy genetika   patologie   MeSH
• receptor erbB-2 genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH