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. 2014 Nov 25;111(11):2114-21.
doi: 10.1038/bjc.2014.500. Epub 2014 Sep 30.

SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma

J Dhanda  1 , A Triantafyllou  2 , T Liloglou  1 , H Kalirai  1 , B Lloyd  1 , R Hanlon  3 , R J Shaw  2 , D R Sibson  1 , J M Risk  1
Affiliations

SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma

J Dhanda et al. Br J Cancer. .

Abstract

Background: Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available.

Methods: In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis.

Results: Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%).

Conclusion: A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.

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Figures

Figure 1
Figure 1
Examples of (A) SMA and (B) SERPINE1 IHC demonstrating distribution of expression at the tumour-advancing front. ( × 5 and × 20 objective). A full colour version of this figure is available at the British Journal Of Cancer journal online.
Figure 2
Figure 2
SMA-advancing front stroma vs ECS.
Figure 3
Figure 3
SERPINE1-advancing front tumour vs ECS.
Figure 4
Figure 4
Venn diagrams showing SMA and SERPINE1 expression vs ECS.
Figure 5
Figure 5
Kaplan–Meier survival curves (OS) for (A) SERPINE1 expression in tumour cells at the tumour-advancing front, (B) SMA expression in the stromal cells at the tumour-advancing front and (C) combined SERPINE1+ and SMA+.
See this image and copyright information in PMC

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