Semiautomatic analysis of tumor proportion in colon cancer: Lessons from a validation study

The tumor stroma ratio (TSR) is a promising histopathologic prognostic biomarker, which could allow for more accurate risk stratification and improved patient management in colorectal cancer. The purpose of our research was to validate the results of a previous study, which had suggested that not only a low but also a high tumor proportion (TP) might be an independent risk factor for occurrence of distant metastasis and worse overall survival using a semiautomatic image analysis approach with the open-source software ImageJ. We investigated 253 pT3 and pT4 adenocarcinomas of no special type. The previously established thresholds (PES-cut-offs) used to classify the patients (previous 3-tiered-classification) according to the tumor proportion (TP) in a highTP (TP ≥ 54%), a mediumTP (TP < 54% ∩ TP >15%) and a lowTP (TP ≤ 15%) group did not show a significant risk stratification. Even the adjustment of these threshold revealed no significant results. Therefore, a receiver-operating characteristic (ROC) analysis was performed to establish the cut-off with the most significant predictive power and a "new 2-tiered-classification" using this cut-off (40% at MinTP) showed a significantly shorter absence of metastasis for patients with a low TP (p = 0.007). These results confirm that a low TP is associated with an adverse prognosis. This study did not confirm the previous assumption that a high TP might also be a risk factor for occurrence of metastasis. Furthermore, it demonstrates that this semiautomatic technique is not superior to the established method, so that approaches to enhance prognostic techniques should continue.