Histological categorisation of fibrotic cancer stroma in advanced rectal cancer

Background and aims: Based on conflicting reports regarding the role of the fibrotic stromal response in cancer development - namely, that a desmoplastic reaction can favour either the host or the tumour - it is clear that the role of the stromal response is varied. We have classified the fibrotic stroma of rectal adenocarcinoma penetrating the muscularis propria, based on histologically identified stromal components. Methods: Three categories of stroma were used: mature - when the stroma was composed of mature collagen fibres ( fine and elongated fibres into multiple layers); intermediate - when keloid-like collagen was intermingled with mature fibres; and immature - consisting of a myxoid stroma in which no mature fibres were included. Results: In a data set of 862 patients, 53% of patients had mature fibrotic cancer stroma, 33% had intermediate stroma, and 15% had immature stroma. Five year survival rates decreased as follows: mature stroma ( 80%), intermediate stroma (55%), and immature stroma (27%). The adverse tumour phenotype, tumour cell budding ( conspicuous isolated cells or small clusters of cancer cells), was observed in the cancer fronts in tumours with unfavourable fibrotic stroma (p< 0.0001). Based on multivariate analysis, categorised fibrotic stroma was selected as an independent prognostic parameter ( hazard ratio 1.39; 95% confidence interval 1.17 - 1.64) together with tumour differentiation. By immunohistochemical examination, as maturation of the fibrotic stroma decreased, stromal T cells became significantly sparser. Furthermore, myofibroblasts were distributed extensively in immature fibrotic stroma compared with mature and intermediate fibrotic stroma. Conclusion: The morphological categorisation of fibrotic cancer stroma highlights the role of the stromal response in relation to the behaviour and host immune reactions of rectal adenocarcinoma and would be a useful tool for predicting patient prognostic outcome.