Korrelation der p53-, EGFR- und SGLT1-Expression im histopathologischen Präparat mit den Nebenwirkungen und dem Outcome einer primären Radio(chemo)Therapie bei Patienten mit lokal fortgeschrittenem Kopf-Hals-Tumor

Correlation of p53-, EGFR and SGLT1-Expression in biopsies of locally advanced, inoperable head and neck cancer with the toxicity and the outcome of a primary radio(chemo)therapy)

by Hannah Siu-Fa Storf
Doctoral thesis
Date of Examination:2018-03-13
Date of issue:2018-03-12
Advisor:PD Dr. Hendrik Wolff
Referee:PD Dr. Hendrik Wolff
Referee:PD Dr. Markus Schirmer
Referee:Prof. Dr. Rainer Mausberg
Persistent Address: http://dx.doi.org/10.53846/goediss-6759

 

 

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Abstract

English

Purpose: To test for a possible correlation between the expression of p53, EGFR and SGLT1 in biopsies of locally advanced, inoperable head and neck cancer with the toxicitiy and the outcome of a primary radio(cehmo) therapy Patients and Methods: from 1994 to 2011, 233 HNSCC patients were treated with radio(chemo)therapy in primary approach. They recevied a normofractionated (2Gy/fraction) irradiation inculuding associted nodal drainage sites to a cumulative dose of 70 Gy. 170 patients received additional concominant chemotherapy (93 5-Fluoruracil/mitomycin c, 1, mitomycin c, 67 platin-based, 9 cetuximab). Toxicity was monitored weekly according tot he Common Toxicity Criteria during treatment as well as drung the follwo up. The pre-treatment biopsies were formalin-fixed and paraffin embedded, immunhistochemically stained with the antibodies DO-7 (p53), 31G7 (EGFR),N3C3 (SGLT1) and semiquantitavely analysed. Results: No statiscally significant coherency between tthe expression of p53, EGFR or SGLT1 in tumorbiopsies and high-grad toxicity of a primary radiochemotherapie could be found. However there was a statistically significant correlation between cytoplasmatic p53 to dysphagia 0-3 as well as nuclear EGFR and dysphagia as well as nausea. Furthermore the cytoplasmatic expression of p53 as well as the membraneous expression of EGFR showed a statistically significant correlation to the endpoints oft the study (overall survival,locoregninal control). Coclusion :These data could not show a significant coherency between the investigated molecular markers p53, EGFR and SGLT1 and the toxicitiy of a primary radiochemotherapie in patients with high grade HNSCC. As far as the expression of p53 and EGFR is concernd a statistic singificant correlation to overall survival and locoregional control could be shown. Further studies are necessary to detect the molecular mechanisms of treatment toxicity and enable an individualised yet effective treatment regimen.
Keywords: locally advanced, inoperable head and neck cancer; primary radio(chemo) therapy; p53; EGFR; SGLT1
Schlagwörter: lokal fortgeschrittene Kopf Hals Tumore; primäre Radio(chemo)Therapie; p53; EGFR; SGLT1
 
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