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Cellular Oncology

, Volume 41, Issue 5, pp 517–525 | Cite as

Stromal collagen type VI associates with features of malignancy and predicts poor prognosis in salivary gland cancer

  • Linus AngenendtEmail author
  • Jan-Henrik Mikesch
  • Dennis Görlich
  • Alina Busch
  • Irina Arnhold
  • Claudia Rudack
  • Wolfgang Hartmann
  • Eva Wardelmann
  • Wolfgang E. Berdel
  • Markus Stenner
  • Christoph Schliemann
  • Inga GrünewaldEmail author
Original Paper

Abstract

Purpose

Collagen Type VI (COLVI) is an extracellular matrix protein that is upregulated in various solid tumours during tumour progression and has been shown to stimulate proliferation, suppress apoptosis and promote invasion and metastasis. It has also been described as a mediator of chemotherapy resistance and as a therapeutic target in preclinical cancer models. Here, we aimed to analyse the prognostic role of COLVI in salivary gland cancer (SGC).

Methods

Stromal COLVI protein expression was assessed in primary SGC specimens of 91 patients using immunohistochemistry (IHC). The IHC expression patterns obtained were subsequently correlated with various survival and clinicopathological features, including Ki-67 and p53 expression.

Results

We found that COLVI was expressed in all SGC specimens. High expression was found to be associated with features of malignancy such as high histologic grades, advanced and invasive T stages and metastatic lymph node involvement (p < 0.05 for all variables). COLVI expression was also found to correlate with both Ki-67 and p53 expression (p < 0.01). We found that high COLVI expression predicted a significantly inferior 5-year overall survival (38.3%, 55.1% and 93.8%; p = 0.002) and remained a significant predictor of prognosis in a multivariate Cox regression analysis (hazard ratio, 2.62; 95% confidence interval, 1.22–5.61; p = 0.013). In all low-risk subgroups COLVI expression identified patients with an adverse outcome. Patients receiving adjuvant radiotherapy had a poor survival when expressing high levels of COLVI.

Conclusions

Our data indicate that stromal COLVI expression associates with key features of malignancy, represents a novel independent prognostic factor and may affect response to radiotherapy in SGC. Although our results warrant validation in an independent cohort, assessing stromal COLVI expression may be suitable for future diagnostic and therapeutic decision making in patients with SGC.

Keywords

Salivary gland carcinoma Parotid cancer Collagen type VI Tissue microarray Prognosis 

Notes

Funding

This work was supported by the fund “Innovative Medical Research” of the University of Münster Medical School (grants SC211008 (C.S.), SC111411 (C.S.), and SC221410 (L.A. and C.S.)). W.E.B. is supported by the Deutsche Forschungsgemeinschaft (DFG EXC 1003, Cluster of excellence “Cells in Motion”).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

13402_2018_389_MOESM1_ESM.docx (290 kb)
ESM 1 (DOCX 290 kb)

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Copyright information

© International Society for Cellular Oncology 2018

Authors and Affiliations

  • Linus Angenendt
    • 1
    Email author
  • Jan-Henrik Mikesch
    • 1
  • Dennis Görlich
    • 2
  • Alina Busch
    • 3
  • Irina Arnhold
    • 1
  • Claudia Rudack
    • 4
  • Wolfgang Hartmann
    • 5
  • Eva Wardelmann
    • 5
  • Wolfgang E. Berdel
    • 1
  • Markus Stenner
    • 4
  • Christoph Schliemann
    • 1
  • Inga Grünewald
    • 5
    Email author
  1. 1.Department of Medicine AUniversity Hospital MünsterMünsterGermany
  2. 2.Institute of Biostatistics and Clinical ResearchUniversity of MünsterMünsterGermany
  3. 3.Department of Internal Medicine IIUniversity Hospital EppendorfHamburgGermany
  4. 4.Department of Otorhinolaryngology, Head and Neck SurgeryUniversity Hospital of MünsterMünsterGermany
  5. 5.Gerhard-Domagk-Institute of PathologyUniversity Hospital MünsterMünsterGermany

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