Etablierung neuer immunhistochemischer Marker zur Unterscheidung von Plattenepithelkarzinomen der Lunge und des HNO-Traktes

Establishment of new immunohistochemical markers for the differentiation of squamous cell carcinoma of the lung and the head-and-neck region

by Jasmin Joost
Doctoral thesis
Date of Examination:2021-05-18
Date of issue:2021-05-06
Advisor:PD Dr. Felix Bremmer
Referee:PD Dr. Dr. Phillipp Brockmeyer
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-8535

 

 

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Abstract

English

Patients with head and neck squamous cell carcinoma (HNSCC) can develop both pulmonary metastases (metHNSCC) and metachronous primary squamous cell carcinomas of the lung (SQCLC) in the course of their disease. Despite the crucial importance for the prognosis of the affected patients and the resulting therapy, the differentiation of these two entities is often complicated because of their overlapping morphology, etiology and biology. Reliable biomarkers to differentiate the entities are lacking so far, so the differential diagnosis is mainly based on radiological and clinical criteria. Regarding this problem, the aim of this dissertation was the establishment of immunohistochemical biomarkers that support the differentiation of SQCLC from HNSCC and its pulmonary metastases. By using high-resolution mass spectrometry in combination with stable isotope labeling by amino acids in cell culture (SILAC), we identified 397 proteins that were expressed significantly differently in HNSCC and SQCLC cell cultures. Of these proteins, CAV1, CAV2, LGALS1 and LGALS7 showed the most promising results. We therefore used them in a verifying immunohistochemical study on tissue samples from 98 SQCLC and 96 HNSCC. In the statistical analysis of the immunohistochemical examination, all four proteins showed significantly higher expression scores in the HNSCC, analogous to the mass spectrometric results. Considering the statistical quality criteria, we found CAV1 (sensitivity: 89.9%, specificity: 66.3%, AUC: 0.781) and LGALS7 (sensitivity: 94.5%, specificity: 66.0%, AUC: 0.802) to be the most suitable marker candidates for the differentiation between SQCLC and HNSCC. The combination of CAV1 and LGALS7, in the sense of an antibody panel, further improved the statistical quality criteria with a sensitivity of 87.2%, a specificity of 87.9% and an AUC of 0.876 and could therefore determine the origin of squamous cell carcinoma with high accuracy.
Keywords: Squamous cell lung carcinoma; head and neck squamous cell carcinoma; lung metastases; second primary tumor; SILAC; immunohistochemistry; CAV1; CAV2; LGALS1; LGALS7; antibody panel
 
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