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

Ueno, Hideki MD*; Kanemitsu, Yukihide MD; Sekine, Shigeki MD; Ishiguro, Megumi MD§; Ito, Eisaku MD; Hashiguchi, Yojiro MD; Kondo, Fukuo MD#; Shimazaki, Hideyuki MD**; Kajiwara, Yoshiki MD*; Okamoto, Koichi MD*; Mochizuki, Satsuki PhD*; Tsujimoto, Hironori MD*; Shinto, Eiji MD*

The American Journal of Surgical Pathology: August 2019 - Volume 43 - Issue 8 - p 1015–1022
doi: 10.1097/PAS.0000000000001272
Original Articles

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.

Departments of *Surgery

**Laboratory Medicine, National Defense Medical College, Tokorozawa

Department of Colorectal Surgery, National Cancer Center Hospital

Molecular Pathology Division, National Cancer Center Research Institute

§Department of Chemotherapy and Oncosurgery, Tokyo Medical and Dental University Medical Hospital

Department of Pathology, Tokyo Medical and Dental University

Department of Surgery, Teikyo University School of Medicine

#Department of Pathology, Teikyo University Hospital, Tokyo, Japan

Conflicts of Interest and Source of Funding: Supported by a Grant-in-Aid for Scientific Research (C) by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 25462075.

Correspondence: Hideki Ueno, MD, Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan (e-mail:

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