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1.
Pathol Res Pract ; 255: 155183, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38364651

RESUMEN

Epithelial ovarian cancers (EOC) associated with germline or somatic BRCA pathogenetic variants have a significantly higher rate of TP53aberrations. The majority of TP53 mutations are detectable by immunohistochemistry and several studies demonstrated that an abnormal p53 pattern characterized high-grade EOCs. An abnormal p53 immunohistochemical staining in fallopian tube (serous tubal intraepithelial carcinoma (STIC) and "p53 signature" is considered as a precancerous lesion of high-grade EOCs and it is often found in fallopian tube tissues of BRCA germline mutated patients suggesting that STIC is an early lesion and the TP53 mutation is an early driver event of BRCA mutated high-grade EOCs. No relevant data are present in literature about the involvement of p53 abnormal pattern in EOC carcinogenesis of patients negative for germline BRCA variants. We describe TP53 mutation results in relationship to the immunohistochemical pattern of p53 expression in a series of EOCs negative for BRCA1 and BRCA2 germline mutations. In addition, we also investigated STIC presence and "p53 signature" in fallopian tube sampling of these EOCs. Our results demonstrate that TP53 alterations are frequent and early events in sporadic EOCs including also low-grade carcinomas. Also in this series, STIC is associated with an abnormal p53 pattern in fallopian tubes of high-grade EOCs. In summary, TP53 aberrations are the most frequent and early molecular events in EOC carcinogenesis independently from BRCA mutation status.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Proteína BRCA1/análisis , Mutación de Línea Germinal , Neoplasias Ováricas/patología , Proteína p53 Supresora de Tumor/metabolismo , Proteína BRCA2/análisis , Trompas Uterinas/química , Trompas Uterinas/metabolismo , Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/genética , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/patología , Cistadenocarcinoma Seroso/patología , Mutación , Carcinogénesis/patología , Células Germinativas/patología
2.
Genes (Basel) ; 14(11)2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-38003003

RESUMEN

(1) Background: MLH1 hypermethylation is an epigenetic alteration in the tumorigenesis of colorectal cancer (CRC) and endometrial cancer (EC), causing gene silencing, and, as a consequence, microsatellite instability. Commonly, MLH1 hypermethylation is considered a somatic and sporadic event in cancer, and its detection is recognized as a useful tool to distinguish sporadic from inherited conditions (such as, Lynch syndrome (LS)). However, MLH1 hypermethylation has been described in rare cases of CRC and EC in LS patients. (2) Methods: A total of 61 cancers (31 CRCs, 27 ECs, 2 ovarian cancers, and 1 stomach cancer) from 56 patients referred to cancer genetic counselling were selected for loss of MLH1 protein expression and microsatellite instability. All cases were investigated for MLH1 promoter methylation and MLH1/PMS2 germline variants. (3) Results: Somatic MLH1 promoter hypermethylation was identified in 16.7% of CRC and in 40% of EC carriers of MLH1 germline pathogenic variants. In two families, primary and secondary MLH1 epimutations were demonstrated. (4) Conclusions: MLH1 hypermethylation should not be exclusively considered as a sporadic cancer mechanism, as a non-negligible number of LS-related cancers are MLH1 hypermethylated. Current flow charts for universal LS screening, which include MLH1 methylation, should be applied, paying attention to a patient's family and personal history.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Endometriales , Femenino , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Homólogo 1 de la Proteína MutL/genética , Inestabilidad de Microsatélites , Predisposición Genética a la Enfermedad , Metilación de ADN/genética , Neoplasias Endometriales/diagnóstico , Carcinogénesis/genética
3.
J Clin Pathol ; 70(9): 792-797, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28416640

RESUMEN

Microsatellite instability (MSI) testing is tricky in gynaecological cancers (GC). Thus, we aimed to describe the instability patterns to improve MSI test interpretation in sporadic and hereditary GCs. Ninety-five cases, including uterine and ovarian cancers, with known genetic and immunohistochemical (IHC) features, were analysed for MSI by a mononucleotide repeats pentaplex (MRP). We identified 13 ambiguous cases that did not fully meet MSI criteria ('borderline' cases, B-MSI), which were mainly represented by MSH2/MSH6-deficient and Lynch syndrome cases. Also, we evaluated nine additional loci of candidate MSI markers that did not improve the detection of MSI cases, but might be useful for discordant or borderline samples. In conclusion, although MSI and IHC test are highly concordant, a subset of ambiguous MSI cases deserves a careful interpretation in particular when MSH2/MSH6 are involved. RPL22 and SRPR testing may be useful to integrate MRP panel for the analysis of critical cases.


Asunto(s)
Biomarcadores de Tumor/genética , Inestabilidad de Microsatélites , Repeticiones de Microsatélite , Neoplasias Ováricas/genética , Neoplasias Uterinas/genética , Biomarcadores de Tumor/análisis , Reparación de la Incompatibilidad de ADN , Enzimas Reparadoras del ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Inmunohistoquímica , Técnicas de Diagnóstico Molecular , Neoplasias Ováricas/química , Neoplasias Ováricas/patología , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Neoplasias Uterinas/química , Neoplasias Uterinas/patología
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