Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or cytological specimens based on cytomorphology; however in ambiguous cases diagnosis requires additional support by immunohistochemistry. While TP53 and RB1 alterations with secondary overexpression of p16 are mainstay events in SCLC pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not yet been fully investigated. We examined the expression of p16, CD56, synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary carcinoids and non-small cell lung carcinomas, and compared diagnostic performance of these markers in the diagnosis of SCLC. P16 was positive in 95 of 101 SCLCs, and displayed highest diagnostic sensitivity of ~94%. Composite biomarkers CD56+p16+TTF1 and CD56+p16+SYP were both able to detect correctly all SCLC cases. Importantly, three (~3%) SCLC cases completely negative for all conventional markers displayed diffuse positivity for p16. CD56 and p16 demonstrated highest concordance between paired small biopsy and cytology specimens. 50% of squamous cell carcinomas, ~41% of adenocarcinoma/NSCLC-favour adenocarcinoma cases, and ~93% of extrapulmonary small cell carcinomas also showed p16-positivity. Combination of CD56, p16 and TTF1 produced diagnostic classifier that outperformed best single marker CD56 in differential diagnosis between SCLC and NSCLC. In conclusion, in the appropriate morphological context p16 represents a useful supplementary marker for diagnosis of SCLC, even in cases where only cytological material is available.

• Klíčová slova
• Immunohistochemistry, Neuroendocrine carcinoma, Non-small cell lung carcinoma, Poorly differentiated, Small cell lung carcinoma, p16,
• MeSH
• biopsie MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• geny p16 fyziologie   MeSH
• imunohistochemie metody   MeSH
• karcinoid diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom diagnóza   patologie   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory plic patologie   MeSH
• nemalobuněčný karcinom plic patologie   MeSH
• plíce patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom diagnóza   patologie   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
• Názvy látek
• nádorové biomarkery MeSH

BACKGROUND: Predictive testing is a crucial part of the complete diagnostic process of non-small cell lung cancer (NSCLC) and a necessary requirement in order to determine proper course of treatment. However, the possibilities of testing and the spectrum of examined markers are quickly evolving as a result of the progress in diagnostic and therapeutic possibilities, and as such it is necessary to regularly update the current guidelines to achieve proper standards of care in routine practice. PURPOSE: To provide a complex overview of the current problematics of predictive testing in NSCLC at a molecular level, considering also the evaluation of PD-L1 expression based on the international and national guidelines. To summarize the current state of predictive testing employed in NSCLC in the Czech Republic. CONCLUSION: Predictive testing in NSCLC is a part of routine diagnostic practice; however, as a result of the expanding spectrum of diagnostic and therapeutic possibilities, it is undergoing significant development. The existing method of the sequential testing of individual markers is becoming unsuitable; given the increasing number of potential predictors and complex molecular testing, the use of new generation sequencing appears to represent a more suitable solution. The immunohistochemical evaluation of PD-L1 expression is also a necessary part of predictive testing in NSCLC.

• Klíčová slova
• PD-L1, driver mutations, non-small cell lung cancer, non-small cell lung carcinoma, predictive testing,
• MeSH
• časná detekce nádoru metody   MeSH
• lidé MeSH
• mutace * MeSH
• nádorové biomarkery genetika   MeSH
• nádory plic diagnóza   genetika   MeSH
• nemalobuněčný karcinom plic diagnóza   genetika   MeSH
• prediktivní hodnota testů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH

BACKGROUND: MicroRNAs are small non-coding one-stranded RNA molecules that play an important role in the post-transcriptional regulation of genes. Bioinformatic predictions indicate that each miRNA can regulate hundreds of target genes. MicroRNA expression can be associated with various cellular processes leading to the metastasis of malignant tumours including non-small cell lung carcinoma. This review summarizes current knowledge on the role of microRNAs in NSCLC metastasis to the brain and lymph nodes. METHODS: A search of the NCBI/PubMed database for publications on expression levels and the mechanisms of microRNA action in NSCLC metastasis. RESULTS AND CONCLUSION: Dysregulation of microRNAs in NSCLC can be associated with brain and lymph node metastasis. There are differences in microRNA expression profiling between NSCLC with and without metastases but it is currently not possible to reliably predict the site of metastasis in NSCLC. Based on data from RNAmicroarrays, bioinformatics analysis is able to predict the target genes of highlighted microRNAs, providing us with complex information about cancer cell features such as enhanced proliferation, migration and invasion. Such microRNAs may then be knocked-down using siRNAs or substituted with miRNA mimics. RNA microarray profiling may thus be a useful tool to select up- or down-regulated microRNAs. A number of authors suggest that microRNAs could serve as biomarkers and therapeutic targets in the treatment of NSCLC metastasis.

• Klíčová slova
• brain metastasis, lymph node metastasis, microRNA, non-small cell lung carcinoma,
• MeSH
• down regulace MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• metastázy nádorů MeSH
• mikro RNA fyziologie   MeSH
• nádorové buněčné linie MeSH
• nádory kostí sekundární   MeSH
• nádory mozku sekundární   MeSH
• nádory plic etiologie   MeSH
• nemalobuněčný karcinom plic etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH

As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small-cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (p < 0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (p = 0.004, n = 35) and three (p = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) (p = 0.047, n = 31) and mediastinal/subcarinal lymph nodes (pN2) (p = 0.021, n = 18) as opposed to grade one tumors (p = 0.688, n = 7) and tumors without lymph node metastases (p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK expression greater than the median value was associated with longer survival (p = 0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients.

• Klíčová slova
• BOK, Bcl-2 family, apoptosis, epithelial-to-mesenchymal transition, non-small-cell lung carcinoma,
• MeSH
• adenokarcinom genetika   metabolismus   sekundární   MeSH
• apoptóza * MeSH
• epitelo-mezenchymální tranzice MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory plic genetika   metabolismus   patologie   MeSH
• nemalobuněčný karcinom plic genetika   metabolismus   sekundární   MeSH
• prognóza MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• spinocelulární karcinom genetika   metabolismus   sekundární   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• BOK protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-bcl-2 MeSH

BACKGROUNDS: Small cell carcinoma (SCC) is characterised by high metastatic potential and the possibility to metastasize to practically any tissue. Small cell carcinoma of the ovary (SCCO) has a very poor prognosis and patients usually die within one year of the initial diagnosis. Breast metastases from SCCO are extremely rare. CASE: We present a 67-year-old female patient with SCCO who initially presented with bone and bilateral breast metastases. Considering the clinical presentation, the patient's age, the absence of hypercalcemia and histological characteristics, a diagnosis of pulmonary type SCCO was made. There was no tumour present in the lungs at the time of the initial diagnosis and thus we ruled out pulmonary SCC. RESULTS: Initially, the patient was treated with radiotherapy of the bone lesion and systemic chemotherapy (etoposide with carboplatin) with the result of partial remission. Then, radical abdominal surgery was performed. Six months later she was diagnosed with progressive disease in the bone, soft tissue including the breast as well as new lesions in the right kidney, pelvis and lungs. She was treated with 2nd line chemotherapy (topotecan with cisplatin) with the result of progressive disease. Because of mediastinal lymphadenopathy, which was causing tracheobronchial compression, radiotherapy was administered with a good palliative outcome. Nine months later, multiple brain metastases were diagnosed and she was treated with whole brain radiotherapy. Shortly after brain irradiation, her status deteriorated rapidly and she died two years after her initial SCCO diagnosis. CONCLUSION: Extrapulmonary small cell carcinoma is a clinicopathological entity distinct from pulmonary small cell carcinoma. It is very rare and therefore there is very little information available regarding treatment of this disease. In contrast to experience in the treatment of pulmonary small cell cancers, prolonged survival is not common.

• MeSH
• lidé MeSH
• malobuněčný karcinom sekundární   MeSH
• nádory kostí sekundární   MeSH
• nádory prsu sekundární   MeSH
• nádory vaječníků patologie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.

• Klíčová slova
• lung cancer, microbiota, non-small cell lung carcinoma, oncogenic mutations,
• MeSH
• adenokarcinom * MeSH
• lidé MeSH
• mikrobiota * MeSH
• nádory plic * mikrobiologie   patologie   MeSH
• nemalobuněčný karcinom plic * mikrobiologie   patologie   MeSH
• spinocelulární karcinom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Small cell lung carcinoma (SCLC) is a high grade neuroendocrinne tumour accounting for approximately 15 % of lung cancers. It is characterised by early relapse and low survival rate. The treatment has remained unchanged for decades. Histological and cytological characteristics are summarised in brief, along with genetic alterations of the tumour. A new molecular subtype classification is presented according to the expression of transciptional factors ASCL1 (SCLC-A), NEUROD1 (SCLC-D), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). These subtypes represent different ways of tumorigenesis, and the distinct genomic alterations may offer new therapeutic strategies.

• Klíčová slova
• NEUROD1, POU2F3, YAP1, small cell lung cancer, small cell lung carcinoma– ASCL1,
• MeSH
• karcinogeneze * genetika   MeSH
• lidé MeSH
• malobuněčný karcinom plic * klasifikace   genetika   patologie   terapie   MeSH
• regulace genové exprese u nádorů MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• transkripční faktory MeSH

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

• Klíčová slova
• IdyllaTM, epidermal growth factor receptor, gene amplification, gene mutation, small cell lung cancer,
• MeSH
• erbB receptory * genetika   MeSH
• formaldehyd MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• malobuněčný karcinom plic * diagnóza   genetika   MeSH
• mutace MeSH
• mutační analýza DNA metody   MeSH
• nádory plic * diagnóza   MeSH
• nemalobuněčný karcinom plic diagnóza   MeSH
• parafín MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• EGFR protein, human MeSH Prohlížeč
• erbB receptory * MeSH
• formaldehyd MeSH
• parafín MeSH

• MeSH
• lidé MeSH
• lymfadenektomie * MeSH
• nádory plic chirurgie   MeSH
• nemalobuněčný karcinom plic chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Small cell lung carcinoma (SCLC) is the most aggressive of lung tumors, metastasize widely and are virtually incurable by surgical means. Therefore, the classification of lung cancer into SCLC and non-small cell lung carcinoma is essential for disease prognosis and treatment. For this purpose we have compared the immunohistochemical distribution of different cytoskeletal proteins as tumor markers. Analysis was performed by using of monoclonal antibodies directed against cytokeratins, neurofilaments, betaIII-tubulin, epithelial membrane antigen and neuron-specific enolase. Our results indicate that keratin and epithelial membrane antigen are reliable epithelial markers for SCLC. In addition, the positive staining with monoclonal antibodies TU-20 against betaIII-tubulin and neuron-specific enolase was found in some cases of SCLC. We suggest, that these antibodies could be a useful tool for complex immunohistochemical diagnosis of SCLC.

• MeSH
• cytoskeletální proteiny metabolismus   MeSH
• fosfopyruváthydratasa metabolismus   MeSH
• imunohistochemie MeSH
• keratiny metabolismus   MeSH
• lidé MeSH
• malobuněčný karcinom diagnóza   metabolismus   patologie   MeSH
• monoklonální protilátky MeSH
• mucin 1 metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory plic diagnóza   metabolismus   patologie   MeSH
• tubulin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytoskeletální proteiny MeSH
• fosfopyruváthydratasa MeSH
• keratiny MeSH
• monoklonální protilátky MeSH
• mucin 1 MeSH
• nádorové biomarkery MeSH
• tubulin MeSH