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dc.contributor.authorDaher, Tamás
dc.date.accessioned2023-03-16T20:17:59Z
dc.date.available2018-11-02T07:18:17Z
dc.date.available2023-03-16T20:17:59Z
dc.date.issued2018
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:hebis:26-opus-137958
dc.identifier.urihttps://jlupub.ub.uni-giessen.de//handle/jlupub/15232
dc.identifier.urihttp://dx.doi.org/10.22029/jlupub-14614
dc.description.abstractHead and neck squamous cell carcinoma (HNSCC) is a malignant epithelial disease arising from the mucosa of the upper aerodigestive tract. It is the 6th most common malignancy worldwide with approximately 650 000 new cases diagnosed each year. In patients with HNSCC, the chance of acquiring a second malignancy in the lung is about 5.4%. Differentiation between a lung metastasis of a HNSCC and a second primary squamous cell carcinoma of the lung (LSCC) remains one of the most difficult tasks in diagnostic pathology, although differentiation would be crucial because of the highly different therapeutic regimes. In most cases traditional morphological examinations fail to find the origin of the lung tumor, so that a reliable method of differentiation is desperately needed. Differentiation has to be made between two major types of HNSCC; HPV-associated and non-HPV-associated tumors which are caused by tobacco smoking and alcohol consumption and harbor TP53 mutations in most of the cases. Researchers have tried to differentiate between lung metastasis and second primary comparing HPV-status of the head and neck and the lung tumors with some success, but in case of negativity of both tumors further analysis is needed. In the past few years, next generation sequencing technology (NGS) has been established worldwide and also in our institute of pathology. This method has the advantage, that mutations of all coding exones of the TP53 gene can be examined in a time-effective high-troughput way. We hypothetised, that comparing the mutations of the HNSCC and LSCC can lead to a decision on lung tumor origin. In our study 65 head and neck squamous cell carcinomas and lung squamous cell carcinomas of 32 patients were analysed. We combined p16 immunohitochemistry and HPV typing to compare HPV status of the tumors in the hope to differentiate between these two entities in the lung. In case of HPV negativity in both tumors we performed a targeted next generation sequencing of all coding exones (exon 2-11) of the TP53 gene to compare mutation status. With the use of HPV analysis only, a decision on lung tumor origin could be made in 2 of the 32 cases (6%). With the use of targeted next generation sequencing of all coding exones of the TP53 gene we could make a decision in 29 of 32 cases (90%). Analysis of clinical records showed, that lung tumor origin has been identified correctly in only 13 out of 29 cases (45%). Furthermore, 11 out of 23 patients (48%) for whom mutational profiling data had not been available, had not received the most suitable treatment. We conclude, that NGS of all TP53 exones in these tumors can lead to better therapeutic decisions.en
dc.language.isoende_DE
dc.rightsIn Copyright*
dc.rights.urihttp://rightsstatements.org/page/InC/1.0/*
dc.subject.ddcddc:610de_DE
dc.titleComparative TP53 targeted next generation sequencing analysis as a diagnostic tool for determining lung tumor origin in patients with head and neck squamous cell carcinoma and synchronous / metachronous squamous cell lung carcinomaen
dc.title.alternativeVergleichende TP53 targeted next-generation Sequenzierung zur Unterscheidung von Metastasen und Zweittumoren der Lunge bei Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereichs und synchronen / metachronen Plattenepithelkarzinomen der Lungede_DE
dc.typedoctoralThesisde_DE
dcterms.dateAccepted2018-10-25
local.affiliationFB 11 - Medizinde_DE
thesis.levelthesis.doctoralde_DE
local.opus.id13795
local.opus.instituteInstitut für Pathologiede_DE
local.opus.fachgebietMedizinde_DE


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