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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)
Author(s) -
Stangl Stefan,
Tontcheva Nikoletta,
Sievert Wolfgang,
Shevtsov Maxim,
Niu Minli,
Schmid Thomas E.,
Pigorsch Steffi,
Combs Stephanie E.,
Haller Bernhard,
Balermpas Panagiotis,
Rödel Franz,
Rödel Claus,
Fokas Emmanouil,
Krause Mechthild,
Linge Annett,
Lohaus Fabian,
Baumann Michael,
Tinhofer Inge,
Budach Volker,
Stuschke Martin,
Grosu AncaLigia,
Abdollahi Amir,
Debus Jürgen,
Belka Claus,
Maihöfer Cornelius,
Mönnich David,
Zips Daniel,
Multhoff Gabriele
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31213
Subject(s) - hsp70 , medicine , prognostic variable , tumor progression , heat shock protein , cancer research , oncology , pathology , overall survival , biology , cancer , biochemistry , gene
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.