The tumor-stroma ratio (TSR) has been reported as a strong, independent prognostic parameter in colon cancer as well as in other epithelial cancer types, and may be implemented to routine pathology diagnostics. The TSR is an easy technique, based on routine hematoxylin and eosin stained histological sections, estimating the amount of stroma present in the primary tumor. It links tumors with high stromal content to poor prognosis. The analysis time is less than 2 min with a low inter-observer variation. Scoring of the TSR has been validated in a number of independent international studies. In this manuscript, we provide a detailed technical description of estimating the TSR in colon cancer, including examples, pitfalls, and recommendations.Electronic supplementary materialThe online version of this article (10.1007/s00428-018-2408-z) contains supplementary material, which is available to authorized users.

Background:Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in situ hybridisation, in a unique, large population-based cohort.Patients and methods:The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient was processed for analysis of miR-21 and quantitatively assessed by image analysis.Results:The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS): HR=1.26; 95% CI: 1.15–1.60; P<0.001. In Cox regression analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR=1.41; 95% CI: 1.19–1.67; P<0.001.Conclusion:The present study showed that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited.

PurposeHigh-risk patients with stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better stratification. We investigated the prognostic value of tumour stroma ratio (TSR) and tumour budding (TB).MethodsA nationwide population-based cohort of 573 patients with stage II CC was included. TSR was scored on hematoxylin and eosin sections as low TSR (> 50% stroma) and high TSR (≤ 50% stroma). TB was evaluated in hotspots on pan-cytokeratin stained sections in 10 high power fields (HPF) at the invasive front and classified by the mean number of buds per HPF as high grade budding (≥ 10 buds) or low-grade budding (< 10 buds). The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS).ResultsLow TSR was associated with worse RFS (HR = 1.342 (95% CI 1.006–1.791), p = 0.045) and OS (HR = 1.376 (95% CI 1.016–1.862), p = 0.039). Furthermore, an association was found between low TSR and microsatellite stabile tumours (p < 0.001). The mean number of buds per HPF was associated to TSR with increasing number of buds related to a lower TSR (p = 0.026). No statistically significant prognostic impact of TB regarding OS or RFS was detected.ConclusionsTSR provided valuable prognostic information, and adding TSR to the current risk stratification may contribute to better patient selection. The estimates of TSR and TB were found to be associated, but no prognostic value of TB was documented.