Disentangling the prognostic heterogeneity of stage III colorectal cancer through histologic stromal categorization

Background. Growing evidence suggests the importance of stroma in determining cancer biology and recent studies have identified that genes closely associated with poor prognosis subtypes of colorectal cancer are expressed by the stroma rather than epithelial cancer cells. We aimed to clarify the prognostic value of the novel histologic classification of desmoplastic reaction in stage III colorectal cancer. Methods. A pathologic review was conducted for 466 stage Ill colorectal cancer patients in a single Japanese institution (1999-2006). Desmoplastic reaction was classified as mature, intermediate, or immature according to existence of hyalinized collagen bundles and myxoid stroma, both appear exclusively at the desmoplastic front. An additional 432 patients treated at four independent institutions (2007-2008) were examined as a second cohort to validate the results. Results. According to desmoplastic reaction, 164, 133, and 169 patients were classified as mature, intermediate, and immature, respectively. Five-year relapse-free survival rates were highest in the mature group (86.0%), followed by the intermediate (73.7%) and immature (50.9%) groups. An adverse prognostic impact of desmoplastic reaction was invariably observed in stage IIIB, which contained 71% of stage III cases. Harrell's concordance index for relapse-free survival was greater in desmoplastic reaction (0.66) than any conventional tumor-associated prognostic factors including tumor node metastasis substage (0.62) and tumor grade (0.53). Similar results were observed in the second cohort, wherein desmoplastic reaction categorization was the most influential prognostic factor. Conclusion. Histologic desmoplastic reaction categorization could be a key to solve the issue of prognostic heterogeneity in stage III colorectal cancer, thereby enhancing the value of tumor node metastasis stage. (C)17 Published by Elsevier Inc.