A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.
- MeSH
- adenom genetika patologie MeSH
- karcinom in situ genetika patologie MeSH
- kolorektální nádory genetika patologie MeSH
- lidé MeSH
- metylace DNA MeSH
- mikrosatelitní nestabilita * MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- následné studie MeSH
- prognóza MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- hormonální substituční terapie MeSH
- hormony aplikace a dávkování MeSH
- hyperplazie endometria * chirurgie farmakoterapie genetika klasifikace patofyziologie patologie MeSH
- hysterektomie metody MeSH
- karcinom in situ genetika patofyziologie MeSH
- kombinovaná farmakoterapie MeSH
- komorbidita MeSH
- konzervativní terapie MeSH
- lidé MeSH
- prekancerózy * genetika klasifikace patofyziologie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- aktinická keratóza farmakoterapie genetika MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky terapeutické užití MeSH
- karcinom in situ genetika MeSH
- lidé MeSH
- mutace MeSH
- nádory kůže genetika MeSH
- promotorové oblasti (genetika) MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom genetika MeSH
- telomerasa genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Poor survival of high-grade serous pelvic cancer is caused by a lack of effective screening measures. The detection of exfoliated cells from high-grade serous pelvic cancer, or precursor lesions, is a promising concept for earlier diagnosis. However, collecting those cells in the most efficient way while fulfilling all requirements for a screening approach is a challenge. We introduce a new catheter for uterine and tubal lavage (UtL) and the clinical evaluation of its performance. METHODS/MATERIALS: In study I, the clinical feasibility of the UtL using the new catheter was examined in 93 patients admitted for gynecologic surgery under general anesthesia. In study II, the safety of the UtL procedure was assessed. The pain during and after the UtL performed under local anesthesia was rated on a visual analog scale by 22 healthy women. RESULTS: In study I, the UtL was carried out successfully in 92 (98.9%) of 93 cases by 16 different gynecologists. It was rated as easy to perform in 84.8% of patients but as rather difficult in cancer patients (odds ratio, 5.559; 95% confidence interval, 1.434-21.546; P = 0.007). For benign conditions, dilatation before UtL was associated with menopause status (odds ratio, 4.929; 95% confidence interval, 1.439-16.884; P = 0.016). In study II, the pain during UtL was rated with a median visual analog scale score of 1.6. During a period of 4 weeks after UtL, none of the participants had to use medication or developed symptoms requiring medical attention. The UtL took 6.5 minutes on average. The amount of extracted DNA was above the lower limit for a sensitive, deep-sequencing mutation analysis in all cases. CONCLUSIONS: Our studies demonstrate that the UtL, using the new catheter, is a safe, reliable, and well-tolerated procedure, which does not require elaborate training. Therefore, UtL fulfils all prerequisites to be used in a potential screening setting.
- MeSH
- adenokarcinom diagnóza genetika patologie MeSH
- DNA nádorová genetika MeSH
- dospělí MeSH
- karcinom in situ diagnóza genetika patologie MeSH
- katetrizace škodlivé účinky přístrojové vybavení MeSH
- léčebná irigace škodlivé účinky přístrojové vybavení MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory prsu diagnóza genetika patologie MeSH
- nádory vaječníků diagnóza genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- studie proveditelnosti MeSH
- uterus patologie chirurgie MeSH
- vejcovody patologie chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
High-resolution imaging methods (HRIMs) and biomarkers present the second step of pancreatic cancer (PC) diagnostics in at-risk individuals. These include patients with positive risk factors, early symptoms, nonresponders to the initial antidiabetic therapy, patients older than 50 years of age with new-onset unstable diabetes requiring insulin as well as patients with long-term insulin-non-dependent diabetes and recent (up to 6 months) failure of antidiabetic therapy. The procedures should be started without delay and the co-operation between the primary and tertiary medical centers is highly desirable. An early indication of HRIMs and biomarkers is a prerequisite for the diagnosis of a resectable PC. This publication reviews the recent contribution of HRIMs and biomarkers toward an early diagnosis of PC.
- MeSH
- adenom diagnostické zobrazování genetika metabolismus MeSH
- biologické markery MeSH
- časná detekce nádoru metody MeSH
- cholangiopankreatografie endoskopická retrográdní MeSH
- duktální karcinom pankreatu diagnostické zobrazování genetika metabolismus MeSH
- elastografie MeSH
- endosonografie MeSH
- karcinom in situ diagnostické zobrazování genetika metabolismus MeSH
- lidé MeSH
- magnetická rezonanční cholangiopankreatografie MeSH
- magnetická rezonanční tomografie MeSH
- mikro RNA genetika MeSH
- multidetektorová počítačová tomografie MeSH
- nádory cystické, mucinózní a serózní diagnostické zobrazování genetika metabolismus MeSH
- nádory slinivky břišní diagnostické zobrazování genetika metabolismus MeSH
- PET/CT MeSH
- plektin metabolismus MeSH
- protilátky metabolismus MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. CONCLUSION: Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.
- MeSH
- androgenní receptory analýza biosyntéza genetika MeSH
- čipová analýza tkání MeSH
- dospělí MeSH
- duktální karcinom klasifikace genetika patologie MeSH
- fenotyp MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- karcinom in situ klasifikace genetika patologie MeSH
- karcinom klasifikace genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz klasifikace genetika patologie MeSH
- receptor erbB-2 analýza biosyntéza genetika MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkriptom MeSH
- vývody slinných žláz 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
- práce podpořená grantem MeSH
Podat přehled molekulárních charakteristik a odlišností preinvazivních a invazivních lézí mléčné žlázy. Typ studie: Přehledová práce. Název a sídlo pracoviště: Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha. Materiál a metodika: Přehled literatury. Závěr: Molekulárně genetická charakteristika jednotlivých lézí může identifikací genetických a epigenetických změn typických pro jednotlivé skupiny přispět ke klasifikaci preinvazivních i invazivních nádorů prsu, a tím i k jejich managementu. Vzhledem k často naprosto odlišnému biologickému chování morfologicky shodných preinvazivních i invazivních nádorů je jasné, že klíč k diferenciaci jednotlivých skupin a rozpoznání jejich prognostického významu je ukryt v genomu a event. proteomu konkrétní nádorové buňky.
To present an overview of molecular characteristics and differences of and between preinvasive and invasive breast tumors. DESIGN: Review. SETTING: Oncogynecologic center, Clinic of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital, Prague. MATERIAL AND METHODS: Review of literature. CONCLUSION: Identification of genetic and epigenetic changes in preinvasive and invasive breast tumors can help to better classify these lesions and improve and tailor their clinical management. Due to completely different biological behavior of morphologically identical lesions, it is clear that the matter of classification and clarification of their clinical behavior is hidden inside the entire genome or proteome.
DNA damage response (DDR) is emerging as a physiological anti-cancer barrier in early stages of cancer development, as shown for several types of solid cancers derived from somatic cells. Here we discuss our recently published and unpublished results on the exceptional paucity of such constitutive activation of the DDR machinery in human testicular germ cell tumours (TGCTs), including their common pre-invasive stage of carcinoma in situ (CIS). Our conclusions are supported by immunohistochemical analyses of multiple markers of activated DNA damage signalling, such as the phosphorylated ATM and Chk2 checkpoint kinases and phosphorylated histone H2AX. We propose that the unique lack of DDR activation in TGCTs reflects the biology of their cell of origin, the gonocyte. Furthermore, we propose that the lack of DDR activation avoids the pressure to select for mutations in DDR genes such as p53 or ATM, and the resulting intact DDR machinery may have implications for the exceptional curability of TGCTs by DNA damaging therapies.
- MeSH
- chromozomální aberace MeSH
- germinální a embryonální nádory * genetika patologie terapie MeSH
- invazivní růst nádoru MeSH
- karcinom in situ genetika MeSH
- lidé MeSH
- mutace MeSH
- poškození DNA * MeSH
- referenční hodnoty MeSH
- testikulární nádory * genetika patologie terapie MeSH
- testis fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
This review summarises the existing knowledge on the phenotype of the carcinoma in situ (CIS) cell. CIS is a common pre-invasive precursor of testicular germ cell tumours of adolescents and young adults. These tumours display a variety of histological forms. Classical seminoma proliferates along the germ cell lineage, whereas embryonal carcinoma retains embryonic features and readily differentiates into teratomas that resemble various somatic cell lineages. A thorough review of the gene expression in CIS cells in comparison to normal testicular germ cells and overt tumours supports the view that CIS is a common precursor for both tumour types. Impaired cell differentiation resulting in a partial retention of the embryonic features, associated with an increasing genomic instability may be responsible for a remarkable phenotypic heterogeneity of CIS cells. Depending on the degree of differentiation and pluripotency, CIS cells found in adult patients seem to be predestined for further malignant progression into one or the other of the two main types of overt tumours. A new concept of phenotypic continuity of differentiation of germ cells along germinal lineage with a gradual loss of embryonic features based on the analysis of gene expression in all types of germ cells during their ontogeny is presented in this review. The data point out that despite the phenotypic continuum of gene expression, there are two periods of rapid changes of gene expression: first at the transition from primordial germ cells to pre-spermatogonia, and later during the pubertal switch from the mitotic to meiotic cell division. The persistent expression of embryonic traits in CIS cells, and the high expression of the cell cycle regulators that are typical of mitotic germ cells support our long-standing hypothesis that CIS cells originate from primordial germ cells or gonocytes and not from germ cells in the adult testis.
- MeSH
- antigeny nádorové genetika MeSH
- buněčný cyklus genetika MeSH
- dospělí MeSH
- exprese genu MeSH
- fenotyp * MeSH
- imunohistochemie MeSH
- karcinom in situ * genetika patologie MeSH
- kmenové buňky patologie MeSH
- lidé MeSH
- lidské chromozomy X genetika MeSH
- lidský chromozom Y genetika MeSH
- mladiství MeSH
- nádorová transformace buněk genetika MeSH
- oprava DNA MeSH
- seminom * genetika patologie MeSH
- spermie patologie MeSH
- testikulární nádory * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
