The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

N P West, M Dattani, P McShane, G Hutchins, J Grabsch, W Mueller, D Treanor, P Quirke, H Grabsch, N P West, M Dattani, P McShane, G Hutchins, J Grabsch, W Mueller, D Treanor, P Quirke, H Grabsch

Abstract

Background: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer.

Methods: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses.

Results: Tumours with PoT-low (<or=47%) were associated with significantly lower cancer-specific survival when compared to PoT-high (hazard ratio (HR)=2.087, 95% CI=1.088-4.003, P=0.024). On sub-analysis, the prognostic effect remained significant in colonic tumours (HR=2.474, 95% CI=1.132-5.408, P=0.019) and tumour, node, metastasis stage III disease (HR=3.480, 95% CI=0.325-9.136, P=0.007). Multivariate Cox regression analysis demonstrated that PoT was an independent prognostic marker when adjusted for age, T stage, N stage and extramural vascular invasion (P=0.017).

Conclusion: This study suggests that a low proportion of tumour cells in colorectal cancer is related to poor cancer-specific survival. A relatively quick, inexpensive and well-established method such as point counting on diagnostic tissue sections could be used to identify a subset of patients who may benefit from adjuvant therapy.

Figures

Figure 1
Figure 1
Morphometric method for establishing the PoT. (A) Selection of a 9 mm2 area at the luminal surface of a haematoxylin and eosin-stained representative section of colorectal cancer. A total of 300 points are randomly inserted into the selected area. (B) Annotation of four individual points comprised of tumour and stroma.
Figure 2
Figure 2
Modified receiver operating characteristic curve used to determine the optimal cut off point for PoT for the subsequent survival analyses. The optimal point is determined from the peak of the curve.
Figure 3
Figure 3
The distribution of the proportion of tumour cells across the colorectal cancer patient population.
Figure 4
Figure 4
Kaplan–Meier survival curve after stratification by PoT. Hazard ratio for PoT-low=2.087 (95% confidence interval=1.088–4.003).

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