Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein ́s level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. 28 non-silent mutations were identified in PTEN, twelve of them were novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples ́ IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.
- MeSH
- endometrium metabolismus patologie MeSH
- fosfohydroláza PTEN genetika MeSH
- hyperplazie endometria * genetika patologie MeSH
- lidé MeSH
- mutace MeSH
- nádory endometria * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in ~25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (~32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.
- MeSH
- Alphapapillomavirus * MeSH
- DNA virů genetika MeSH
- imunohistochemie MeSH
- infekce papilomavirem komplikace MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory nosu virologie MeSH
- paranazální dutiny patologie MeSH
- RNA virová MeSH
- spinocelulární karcinom virologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- MeSH
- hybridizace in situ MeSH
- imunohistochemie MeSH
- lidé MeSH
- nádory nosohltanu * diagnóza MeSH
- nazofarynx patologie MeSH
- Papillomaviridae patogenita MeSH
- polymerázová řetězová reakce MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom * diagnóza MeSH
- virus Epsteinův-Barrové patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.
- MeSH
- fosfohydroláza PTEN genetika MeSH
- hyperplazie endometria genetika MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- mutace genetika MeSH
- mutační analýza DNA MeSH
- mutační rychlost MeSH
- nádory endometria genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- cyklosporin terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- psoriáza farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dospělí MeSH
- hypertenze komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- medulla oblongata patologie MeSH
- nemoci mozku epidemiologie etiologie patologie MeSH
- prevalence MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
Infekcie, ktorých póvodcom je Cryptococcus neoformans, sa vyskytujú převážné u pacientov s poruchami funkcie T-lymfocytov, a najma u osob s AIDS.Autoři sa domnievajú, že touto infekciou sú ohrození tiež fudia vyššieho veku, a to aj relativné zdraví. Zaznamenali fatálnu kryptokokovú meningoencefalitídu s fulminantným priebehom u 76-ročnej pacientky bez prejavov imunodeficitu v anamnéze.
Infections caused by Cryptococcus neoformans affect mainly patients with impaired functions oř T-cells, and in particular individuals with AIDS.The authors suppose also older subjects in relatively good health to be endangered by this infection. A čase of fatal cryptococcal meningoencephalitis with fulminant coarse was detected in a 76-year female patient without evident immunodeficiency.
- MeSH
- Cryptococcus neoformans izolace a purifikace patogenita MeSH
- dospělí MeSH
- imunitní systém patologie MeSH
- infekce dýchací soustavy MeSH
- kryptokoková meningitida etiologie patologie terapie MeSH
- lidé MeSH
- meningoencefalitida etiologie patologie terapie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- akutní myeloidní leukemie komplikace terapie MeSH
- algoritmy MeSH
- farmakoterapie škodlivé účinky MeSH
- krvácení terapie MeSH
- lidé MeSH
- počet trombocytů normy statistika a číselné údaje MeSH
- převod jednotlivých krevních složek normy MeSH
- trombocytopenie etiologie patologie terapie MeSH
- Check Tag
- lidé MeSH
