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. 2017 Feb 28;116(5):640-648.
doi: 10.1038/bjc.2016.455. Epub 2017 Jan 17.

Tenascin-C and fibronectin expression divide early stage tongue cancer into low- and high-risk groups

Elias Sundquist  1   2 , Joonas H Kauppila  1   2   3 , Johanna Veijola  4   5 , Rayan Mroueh  6 , Petri Lehenkari  1   2 , Saara Laitinen  7 , Juha Risteli  2   8   9 , Ylermi Soini  10   11 , Veli-Matti Kosma  10   11   12 , Iris Sawazaki-Calone  13 , Carolina Carneiro Soares Macedo  14 , Risto Bloigu  15 , Ricardo D Coletta  14 , Tuula Salo  1   2   16
Affiliations

Tenascin-C and fibronectin expression divide early stage tongue cancer into low- and high-risk groups

Elias Sundquist et al. Br J Cancer. .

Abstract

Background: Oral tongue squamous cell carcinoma (OTSCC) metastasises early, especially to regional lymph nodes. There is an ongoing debate on which early stage (T1-T2N0) patients should be treated with elective neck dissection. We need prognosticators for early stage tongue cancer.

Methods: Mice immunisation with human mesenchymal stromal cells resulted in production of antibodies against tenascin-C (TNC) and fibronectin (FN), which were used to stain 178 (98 early stage), oral tongue squamous cell carcinoma samples. Tenascin-C and FN expression in the stroma (negative, moderate or abundant) and tumour cells (negative or positive) were assessed. Similar staining was obtained using corresponding commercial antibodies.

Results: Expression of TNC and FN in the stroma, but not in the tumour cells, proved to be excellent prognosticators both in all stages and in early stage cases. Among early stages, when stromal TNC was negative, the 5-year survival rate was 88%. Correspondingly, when FN was negative, no cancer deaths were observed. Five-year survival rates for abundant expression of TNC and FN were 43% and 25%, respectively.

Conclusions: Stromal TNC and, especially, FN expressions differentiate patients into low- and high-risk groups. Surgery alone of early stage primary tumours might be adequate when stromal FN is negative. Aggressive treatments should be considered when both TNC and FN are abundant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Characterisation of the new matrix antibodies. Coomassie-stained SDS-7.5% PAGE of the target antigens from the cultured hMSC lysate immunoprecipitated using the new anti-tenascin-C monoclonal antibody D2 (A) or anti-fibronectin monoclonal antibody F12 (B). Molecular weight markers are shown on the left of the gels: Bio-Rad Dual Colour (A) and Sigma Colorburst (B). The identified target antigen is marked with arrows. Bands migrating at ∼60 kDa region are mouse antibody fragments detached from the resin (A). The immunostaining of the synovia tissue sections with anti-tenascin-C D2, anti-fibronectin F12 and idiotype IgG1 as negative control (C). New antibodies were compared with commercial ones by staining representative samples from ‘negative' and ‘abundant' groups using both D2 and commercial DB7 for TNC (D), and both F12 and commercial NCL-FIB for FN (E).
Figure 2
Figure 2
Scoring of stromal and intracellular TNC and FN.Stromal TNC (A–C) and FN (E–G) were scored from 0 to 4 and grade 0 was labelled ‘negative' (A and E), grades 1–3 were combined and labelled ‘moderate' (B and F) and grade 4 was labelled ‘abundant' (C and G). Intracellular TNC (D) and FN (H) were scored from 0 to 2. Grade 0 was labelled ‘negative' and 1–2 were combined and labelled ‘positive' (D and H).
Figure 3
Figure 3
Survival of stage I and II OTSCC patients.Kaplan–Meier curves representing the cumulative survival of early stage OTSCC patients divided by stromal TNC (A) and FN (B) staining, as well as cellular TNC (C) and FN (D). In curves A–D the survivals are shown throughout the entire follow-up time. Five-year survivals are shown separately (E). Log-rank test was used to test statistical significance.
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