Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy : a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

  • Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.
Author:Stefan Stangl, Nikoletta Tontcheva, Wolfgang Sievert, Maxim Shevtsov, Minli NiuORCiDGND, Thomas E. Schmid, Steffi Pigorsch, Stephanie CombsORCiD, Bernhard Haller, Panagiotis BalermpasORCiDGND, Franz RödelORCiDGND, Claus RödelORCiDGND, Emmanouil FokasORCiDGND, Mechthild KrauseORCiDGND, Annett LingeORCiDGND, Fabian LohausORCiDGND, Michael Baumann, Inge Tinhofer, Volker BudachORCiDGND, Martin Stuschke, Anca-Ligia GrosuORCiDGND, Amir AbdollahiORCiDGND, Jürgen Debus, Claus Belka, Cornelius Maihöfer, David Mönnich, Daniel Zips, Gabriele MulthoffORCiD
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29235112
Parent Title (English):International journal of cancer
Place of publication:Bognor Regis
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/12/13
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/01/22
Tag:Hsp70; IHC; NK cells; SCCHN; prognostic biomarker; retrospective trial
Page Number:15
First Page:1911
Last Page:1925
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0