Morphological consistency of desmoplastic reactions between the primary colorectal cancer lesion and associated metastatic lesions

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Some preceding studies show that a desmoplastic reaction (DR) at the invasive front of a primary tumor (DRprimary) is a promising prognostic indicator, and its histologic classification is an independent prognostic factor in patients with colorectal cancer (CRC). Although DR is observed in metastatic lesions, such as those in lymph nodes (DRLN) and the liver (DRliver), the association between DRprimary and DR of metastatic lesions is unclear. We investigated whether DRLN and DRliver could be categorized in the same manner as DRprimary and examined the features and prognostic implications of DRLN and DRliver. In this study, we evaluated 363 patients with metastases to lymph nodes and 45 patients with synchronous liver metastases who underwent curative resection. DRLN and DRliver statuses were classified as mature, intermediate, or immature, based on keloid-like collagen and myxoid stroma appearances in the metastatic lesions. Overall, 109, 106, and 148 patients had mature, intermediate, and immature DRLN, respectively; in total, 5, 21, and 19 patients had mature, intermediate, and immature DRliver, respectively. DRLN and DRprimary (spearman’s rho = 0.43, P < 0.0001) and DRliver and DRprimary (spearman’s rho = 0.40, P = 0.0069) were each significantly correlated. The 5-year relapse-free survival (RFS) after surgery was 67.7% for mature/intermediate DRLN and 52.9% for immature DRLN; the 5-year RFS after hepatectomy was 11.5% for mature/intermediate DRliver and 5.6% for immature DRliver. In conclusion, DRLN and DRliver may be classified in the same manner as DRprimary; morphological consistency of DR was observed between primary and metastatic lesions.

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Fig. 1
Fig. 2



Cancer-associated fibroblast


Colorectal cancer


Desmoplastic reaction


Desmoplastic reaction in the lymph node metastases

DRliver :

Desmoplastic reaction in the colorectal liver metastases

DRprimary :

Desmoplastic reaction in the primary tumor


Overall survival


Relapse-free survival


Metastatic lymph nodes


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The authors would like to thank Dr. Hideyuki Shimazaki from the Department of Laboratory Medicine, National Defense Medical College for providing pathological evaluation.

Author information

Tadakazu Ao and Yoshiki Kajiwara conceived and designed the study, and wrote, edited, and reviewed the manuscript. Keisuke Yonemura collected the data and reviewed the manuscript. Eiji Shinto, Satsuki Mochizuki, Koichi Okamoto, and Yoji Kishi revised the manuscript. Hideki Ueno conceived and designed the study, and reviewed manuscript. All authors approved the final version of the manuscript for publication. Tadakazu Ao takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Correspondence to Yoshiki Kajiwara.

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The experiments reported here were conducted in agreement with the Declaration of Helsinki, and were approved by the Ethics Committee of the National Defense Medical College Hospital (Tokorozawa, Japan).

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The authors declare that they have no conflict of interest.

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Ao, T., Kajiwara, Y., Yonemura, K. et al. Morphological consistency of desmoplastic reactions between the primary colorectal cancer lesion and associated metastatic lesions. Virchows Arch (2020) doi:10.1007/s00428-019-02742-2

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  • Desmoplastic reaction
  • Colorectal cancer
  • Lymphatic metastases
  • Liver metastases
  • Cancer-associated fibroblasts