Tumor Biology

, Volume 36, Issue 12, pp 9929–9939 | Cite as

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

  • Martina Raudenska
  • Marketa Sztalmachova
  • Jaromir Gumulec
  • Michaela Fojtu
  • Hana Polanska
  • Jan Balvan
  • Marek Feith
  • Hana Binkova
  • Zuzana Horakova
  • Rom Kostrica
  • Rene Kizek
  • Michal Masarik
Research Article


Even with significant advances in operative skills and adjuvant therapies, the overall survival of patients suffering with head and neck squamous cancers (HNSCC) is unsatisfactory. Accordingly, no clinically useful prognostic biomarkers have been found yet for HNSCC. Many studies analysed the expression of potential markers in tumour tissues compared to adjacent tissues. Nevertheless, due to the sharing of the same microenvironment, adjacent tissues show molecular similarity to tumour tissues. Thus, gene expression patterns of 94 HNSCC tumorous tissues were compared with 31 adjacent tissues and with 10 tonsillectomy specimens of non-cancer individuals. The genes analysed at RNA level using quantitative RT-PCR and correlated with clinico-pathological conditions were as follows: EGF, EGFR, MKI67, BCL2, BAX, FOS, JUN, TP53, VEGF, FLT1, MMP2, MMP9, MT1A and MT2A. The elevated MT2A, BAX, EGF and JUN expression was associated with the influence of tumour cells on the rearrangement of healthy tissues, as well as a significant shift in the BAX/BCL2 ratio. Our investigation also indicated that adjacent tissues play an important role in cancerogenesis by releasing several tumour-supporting factors such as EGF. A gradual increase in the metallothionein expression, from the lowest one in tonsillectomy samples to the highest ones in tumour samples, suggests that MT expression might be tissue reaction to the presence of tumour cells. The results of this study confirmed the significance of metallothionein in tumori-genesis and gave evidences for its use as a potential HNSCC biomarker. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in prediction of HNSCC progress.


Head and neck neoplasms Biological markers Prognosis Tumour microenvironment Metallothionein Matrix metalloproteinase 9 Gene expression 



This work was supported by the Ministry of Health of the Czech Republic IGA MZ NT 14337-3/2013.

Conflicts of interest


Supplementary material

13277_2015_3755_MOESM1_ESM.pdf (59 kb)
ESM. 1 (PDF 59 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Martina Raudenska
    • 1
    • 2
  • Marketa Sztalmachova
    • 1
    • 2
  • Jaromir Gumulec
    • 1
    • 2
  • Michaela Fojtu
    • 1
    • 2
    • 3
  • Hana Polanska
    • 1
    • 2
  • Jan Balvan
    • 1
    • 2
  • Marek Feith
    • 1
  • Hana Binkova
    • 4
  • Zuzana Horakova
    • 4
  • Rom Kostrica
    • 4
  • Rene Kizek
    • 2
    • 5
  • Michal Masarik
    • 1
    • 2
  1. 1.Department of Pathological Physiology, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  2. 2.Central European Institute of TechnologyBrno University of TechnologyBrnoCzech Republic
  3. 3.Department of Physiology, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  4. 4.Department of Otorhinolaryngology and Head and Neck SurgerySt. Anne’s Faculty HospitalBrnoCzech Republic
  5. 5.Department of Chemistry and BiochemistryMendel University in BrnoBrnoCzech Republic

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