A Multicenter Study of the Prognostic Value of Desmoplastic Reaction Categorization in Stage II Colorectal Cancer

Abstract

Highly accurate risk assessment of recurrence may improve adjuvant treatment practice in stage II colorectal cancer (CRC), which lacks definite prognostic factors. Recent studies indicate the importance of stroma in determining cancer behavior, although there are few histopathologic criteria for its evaluation. A pathology review of 679 stage II CRC patients (1980-2005) was conducted at an institution. Desmoplastic reaction (DR) results were classified as mature, intermediate, or immature depending on the presence of hyalinized collagen bundles and myxoid stroma observed at the extramural desmoplastic front on hematoxylin–eosin-stained slides. Pathologically, 430, 180, and 69 tumors were classified into the mature, intermediate, and immature groups, respectively. On the basis of the DR results, 5-year recurrence rate was found to have a wide range of 9.1% to 30.7%; 5-year relapse-free survival (RFS) rates were highest in the mature group (85.2%), followed by the intermediate (77.1%), and immature (60.9%) groups. Multivariate analyses revealed an independent effect of DR pattern on RFS. In addition, 446 patients treated at 4 independent institutions (2007-2008) were examined as a second cohort for result validation, revealing an adverse prognostic impact of unfavorable DR and identifying DR categorization as an independent prognostic factor. In both cohorts, Harrell’s concordance index for RFS was higher than the other conventional factors in the DR including T stage. Categorizing DR pattern based on the histologic products of fibroblasts at the desmoplastic front help elucidate their important biological role in cancer development, thus providing clinically useful prognostic information regarding stage II CRC.

Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial)

“…49 On the other hand, our previous retrospective multicentre study found that DR categorisation stratified risk of recurrence for two independent cohorts over a wider range in stage II CRC patients; specifically, the cumulative recurrence rate 5 years after surgery ranged between 9-31% in the first cohort and 11-37% in the second cohort. 23 Given that these figures are similar to those presented here, where there is also a clear differentiation in the recurrence rates among the three prognostic groups (8%, 21% and 32% for Mature, Intermediate and Immature, respectively), it is worth revisiting the classic and H&E-oriented surgical pathology when new treatment-deciding factors based on the role of cancer microenvironment emerge. These may include tumour budding 26 and DR pattern, which could improve upon current genetic staging in terms of cost-benefit performance.…”

“…Recent retrospective multicentre studies revealed that the type of DR in a primary tumour affects postoperative prognostic outcomes independently of tumour stage, and this factor may outweigh conventional tumour factors in terms of the power for predicting RFS in early CRC. 19,23,33 These results were validated in this study, in which DR characterisation was prospectively determined in stage II colon cancer and its prognostic value was evaluated employing three different statistical approaches. First, based on the Cox proportional-hazard model, DR characterisation was identified as an independent prognostic factor, along with Tstage and tumour budding.…”

“…This method has been applied subsequently to some individual stages of CRC, including T2 CRC, 16 stage II CRC, 17 stage III CRC, [18][19][20] resectable stage IV CRC 21,22 and unresectable stage IV CRC, 22 in which efficient three-tier survival stratification was consistently found using this method. Furthermore, recent multicentre retrospective studies revealed that a significant survival stratification could be achieved by DR categorisation in stage II CRC patients in Japan 23 and the United Kingdom. 24 In both of these studies, DR categorisation was shown to be the most significant of all the analysed histopathologic features for predicting survival outcome.…”

Stromal categorization in early oral tongue cancer

“…HE-stained slides of resection specimens of early OTSCC were used for the assessment of all stromal features in this study. We categorized desmoplastic reaction based on the maturity of stroma as recently described [11,14] into three groups:…”

“…Regarding the desmoplastic reaction, the stroma has been categorized into mature, intermediate, and immature based on morphology and arrangement of collagen and the myxoid nature of stroma. [14]. Of note, the clinical significance of the desmoplastic reaction has not been studied in early OTSCC.…”