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. 2019 Jun 25;19(1):624.
doi: 10.1186/s12885-019-5816-9.

Expression of toll-like receptors in non-endemic nasopharyngeal carcinoma

Miia Ruuskanen  1 , Ilmo Leivo  2 , Heikki Minn  3 , Tero Vahlberg  4 , Caj Haglund  5   6 , Jaana Hagström  6   7 , Heikki Irjala  8
Affiliations

Expression of toll-like receptors in non-endemic nasopharyngeal carcinoma

Miia Ruuskanen et al. BMC Cancer. .

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer.

Methods: In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome.

Results: We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative).

Conclusions: TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

Keywords: Epstein-Barr virus; Head and neck cancer; Human papillomavirus; Nasopharyngeal carcinoma; Toll-like receptor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
TLR5 and TLR7 expression in nasopharyngeal carcinoma and in the normal epithelium. a H&E staining in non-keratinizing undifferentiated carcinoma (NK-U). b H&E staining in keratinizing squamous cell carcinoma (KSCC). c Mild positive TLR5 expression in NK-U. d Strong positive TLR5 expression in KSCC. e Moderate positive TLR7 expression in NK-U. f Moderate positive TLR7 expression in KSCC. g Positive TLR5 staining in benign nasopharyngeal epithelium. h Positive TLR7 staining in benign nasopharyngeal epithelium. Magnification × 250
Fig. 2
Fig. 2
Score distribution of TLR expressions according to viral status. a TLR2nucl. b TLR5
Fig. 3
Fig. 3
Kaplan-Meier survival curves. a Overall survival for TLR5. b Disease-specific survival for TLR5. c Overall survival for TLR7. d Disease-specific survival for TLR7
See this image and copyright information in PMC

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