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Virchows Archiv
Published in: Virchows Archiv 4/2022

01-04-2022 | Colorectal Cancer | Original Article

Desmoplastic reactions and epithelial-mesenchymal transition proteins in stages II and III colorectal cancer: association with and prognostic value for disease-free survival

Authors: Mai Hashimoto, Noriyuki Uesugi, Mayu Sugai, Kazuhiro Ito, Naoki Yanagawa, Koki Otsuka, Yoshiki Kajiwara, Hideki Ueno, Akira Sasaki, Tamotsu Sugai

Published in: Virchows Archiv | Issue 4/2022

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Abstract

Recent study has shown that there is a close association of desmoplastic reactions (DRs) with the survival of patient with colorectal cancer (CRC). Here, we examined the correlation of DR classification with disease-free survival and overall survival of CRC. Moreover, we also investigated the association of the histological transition of the DR with the expression of cancer-associated fibroblast (CAF)- and epithelial-mesenchymal transition (EMT)-related proteins in CRC in stages II and III. We examined 157 cases of stage II CRC and 163 cases in stage III. We classified DRs into mature, intermediate, and immature types and examined the correlation of the DR patterns with patient survival. Next, the expression of CAF- and EMT-related markers was examined in CRC samples using immunohistochemistry. In stage II CRC, we found a significant correlation of disease-free survival with DR subtype (immature vs mature) in univariate and multivariate analyses. In stage III CRC, however, such association was not identified. Finally, the DR was closely associated with two EMT-related markers in stages II and III CRC. Our findings suggest that classification of the DR may help to predict patient prognosis in CRC. Furthermore, classification of the DR is correlated with the expression of EMT-related proteins.
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Literature
1.
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC et al (2020) Colorectal cancer statistic. CA Cancer J Clin 70(3):145–164CrossRefPubMed
2.
Puppa G, Sonzogni A, Colombari R, Pelosi G (2010) TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med 134(6):837–852CrossRefPubMed
3.
Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H et al (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 30(9):1299–1311CrossRefPubMed
4.
Moccia F, Tolone S, Allaria A, Napolitano V, Rosa D, Ilaria F et al (2019) Lymph node ratio versus TNM system as prognostic factor in colorectal cancer staging. a Single Center Experience. Open Med (Wars) 14:523–531CrossRef
5.
Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 352(5):476–487CrossRefPubMed
6.
Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK (2010) Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol 28(2):264–271CrossRefPubMed
7.
Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, et al 2018. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23(1):1–34.
8.
Ueno H, Ishiguro M, Nakatani E, Hashiguchi Y, Ito Y, Saito Y et al (2021) Prognostic value of desmoplastic reaction characterization in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial). Br J Cancer 124(6):1088–1097CrossRefPubMedPubMedCentral
9.
Calon A, Lonardo E, Berenguer-Llergo A, Ishikawa T, Uetake H, Murotani K et al (2015) Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 47(4):320–329CrossRefPubMed
10.
Becht E, de Reyniès A, Giraldo NA, Pilati C, Buttard B, Lacroix L et al (2016) Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin Cancer Res 22(16):4057–4066CrossRefPubMed
11.
Musa M, Ali A (2020) Cancer-associated fibroblasts of colorectal cancer and their markers: updates, challenges and translational outlook. Future Oncol 16(29):2329–2344CrossRefPubMed
12.
13.
Ueno H, Konishi T, Ishikawa Y, Shimazaki H, Ueno M, Aosasa S et al (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(10):1380–1386CrossRefPubMed
14.
Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Fujikawa H et al (2011) Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy. Int J Oncol 38(3):655–663CrossRefPubMed
15.
Hamilton SR, Sekine S 2019. Conventional colorectal adenoma. WHO classification of tumours of the digestive system. International Agency for Research on Cancer, Lyon 170–173.
16.
Sugai T, Yamada N, Eizuka M, Sugimoto R, Uesugi N, Osakabe M et al (2017) Vascular Invasion and Stromal S100A4 Expression at the invasive front of colorectal cancer are novel determinants and tumor prognostic markers. J Cancer 8(9):1552–1561CrossRefPubMedPubMedCentral
17.
Shim HS, Kenudson M, Zheng Z, Liebers M, Cha YJ, Hoang Ho Q et al (2015) Unique genetic and survival characteristics of invasive mucinous adenocarcinoma of the lung. J Thorac Oncol 10(8):1156–1162CrossRefPubMed
18.
Hashimoto M, Uesugi N, Osakabe M, Yanagawa N, Otsuka K, Kajiwara Y, et al. Expression patterns of microenvironmental factors and tenascin-C at the invasive front of stage II and III colorectal cancer: novel tumor prognostic markers. Front Oncol. 2021;11:690816.
19.
Yang Z, Zhang C, Qi W, Cui C, Cui Y, Xuan Y (2018) Tenascin-C as a prognostic determinant of colorectal cancer through induction of epithelial-to-mesenchymal transition and proliferation. Exp Mol Pathol 105(2):216–222CrossRefPubMed
20.
Murakami T, Kikuchi H, Ishimatsu H, Iino I, Hirotsu A, Matsumoto T et al (2017) Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis. Br J Cancer 117(9):1360–1370CrossRefPubMedPubMedCentral
21.
22.
Tommelein J, Verset L, Boterberg T, Demetter P, Bracke M, De Wever O (2015) Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer. Front Oncol 5:63CrossRefPubMedPubMedCentral
23.
Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R, et al 2015. HIF-1α promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS One 10: e0129603.
24.
Krebs AM, Mitschke J, Lasierra Losada M, Losada M, Schmalhofer O, Boerries M et al (2017) The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol 19(5):518–529CrossRefPubMed
25.
Chen L, Gibbons DL, Goswami S, Cortez MA, Ahn YH, Byers LA et al (2014) Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun 5:5241CrossRefPubMed
26.
Terry S, Savagner P, Ortiz-Cuaran S, Mahjoubi L, Saintigny P, Thiery J et al (2017) New insights into the role of EMT in tumor immune escape. Mol Oncol 11(7):824–846CrossRefPubMedPubMedCentral
Metadata
Title
Desmoplastic reactions and epithelial-mesenchymal transition proteins in stages II and III colorectal cancer: association with and prognostic value for disease-free survival
Authors
Mai Hashimoto
Noriyuki Uesugi
Mayu Sugai
Kazuhiro Ito
Naoki Yanagawa
Koki Otsuka
Yoshiki Kajiwara
Hideki Ueno
Akira Sasaki
Tamotsu Sugai
Publication date
01-04-2022
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 4/2022
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-021-03266-4

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