Morphological consistency of desmoplastic reactions between the primary colorectal cancer lesion and associated metastatic lesions
- 25 Downloads
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.
KeywordsDesmoplastic reaction Colorectal cancer Lymphatic metastases Liver metastases Cancer-associated fibroblasts
Desmoplastic reaction in the lymph node metastases
Desmoplastic reaction in the colorectal liver metastases
Desmoplastic reaction in the primary tumor
Metastatic lymph nodes
The authors would like to thank Dr. Hideyuki Shimazaki from the Department of Laboratory Medicine, National Defense Medical College for providing pathological evaluation.
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.
Compliance with ethical standards
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).
Conflicts of interest
The authors declare that they have no conflict of interest.
- 8.Huijbers A, Tollenaar RA, v Pelt GW, Zeestraten EC, Dutton S, CC MC, Domingo E, Smit VT, Midgley R, Warren BF, Johnstone EC, Kerr DJ, Mesker WE (2013) The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 24:179–185. https://doi.org/10.1093/annonc/mds246 CrossRefPubMedGoogle Scholar
- 10.Karagiannis GS, Poutahidis T, Erdman SE, Kirsch R, Riddell RH, Diamandis EP (2012) Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol Cancer Res 10:1403–1418. https://doi.org/10.1158/1541-7786.Mcr-12-0307 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Shibutani M, Maeda K, Nagahara H, Fukuoka T, Matsutani S, Kashiwagi S, Tanaka H, Hirakawa K, Ohira M (2018) A comparison of the local immune status between the primary and metastatic tumor in colorectal cancer: a retrospective study. BMC Cancer 18:371. https://doi.org/10.1186/s12885-018-4276-y CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Ueno H, Konishi T, Ishikawa Y, Shimazaki H, Ueno M, Aosasa S, Saiura A, Hase K, Yamamoto J (2014) Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis. Am J Surg Pathol 38:1380–1386. https://doi.org/10.1097/pas.0000000000000232 CrossRefPubMedGoogle Scholar
- 22.Ueno H, Shinto E, Hashiguchi Y, Shimazaki H, Kajiwara Y, Sueyama T, Yamamoto J, Hase K (2015) In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis. Virchows Arch 466:655–663. https://doi.org/10.1007/s00428-015-1756-1 CrossRefPubMedGoogle Scholar
- 23.Ueno H, Shinto E, Shimazaki H, Kajiwara Y, Sueyama T, Yamamoto J, Hase K (2015) Histologic categorization of desmoplastic reaction: its relevance to the colorectal cancer microenvironment and prognosis. Ann Surg Oncol 22:1504–1512. https://doi.org/10.1245/s10434-014-4149-9 CrossRefPubMedGoogle Scholar
- 24.Ueno H, Kanemitsu Y, Sekine S, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J (2017) Desmoplastic pattern at the tumor front defines poor-prognosis subtypes of colorectal cancer. Am J Surg Pathol 41:1506–1512. https://doi.org/10.1097/pas.0000000000000946 CrossRefPubMedGoogle Scholar
- 25.Ueno H, Sekine S, Oshiro T, Kanemitsu Y, Hamaguchi T, Shida D, Takashima A, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J, Shimada Y (2018) Disentangling the prognostic heterogeneity of stage III colorectal cancer through histologic stromal categorization. Surgery 163:777–783. https://doi.org/10.1016/j.surg.2017.09.007 CrossRefPubMedGoogle Scholar
- 26.West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H (2010) The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 102:1519–1523. https://doi.org/10.1038/sj.bjc.6605674 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Xu Z, Vonlaufen A, Phillips PA, Fiala-Beer E, Zhang X, Yang L, Biankin AV, Goldstein D, Pirola RC, Wilson JS, Apte MV (2010) Role of pancreatic stellate cells in pancreatic cancer metastasis. Am J Pathol 177:2585–2596. https://doi.org/10.2353/ajpath.2010.090899 CrossRefPubMedPubMedCentralGoogle Scholar