Primary Tumor Histology Affects Oncological Outcomes Independently of the Anatomical Extent of Disease in Colorectal Liver Metastasis
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- Ueno Hideki
- Department of Surgery, National Defense Medical College, Saitama, Japan
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- Konishi Tsuyoshi
- Gastroenterology Center, Cancer Institute Hospital, Tokyo, Japan
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- Ishikawa Yuichi
- Division of Pathology, Cancer Institute Hospital, Tokyo, Japan
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- Shimazaki Hideyuki
- Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan
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- Ueno Masashi
- Gastroenterology Center, Cancer Institute Hospital, Tokyo, Japan
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- Aosasa Suefumi
- Department of Surgery, National Defense Medical College, Saitama, Japan
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- Saiura Akio
- Gastroenterology Center, Cancer Institute Hospital, Tokyo, Japan
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- Shinto Eiji
- Department of Surgery, National Defense Medical College, Saitama, Japan
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- Kajiwara Yoshiki
- Department of Surgery, National Defense Medical College, Saitama, Japan
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- Mochizuki Satsuki
- Department of Surgery, National Defense Medical College, Saitama, Japan
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- Nakamura Takahiro
- Laboratory for Mathematics, National Defense Medical College, Tokorozawa, Japan Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Tokyo, Japan
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- Yamamoto Junji
- Department of Surgery, National Defense Medical College, Saitama, Japan
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Description
<p>Introduction: Growing evidence indicates the prognostic importance of the crosstalk between cancer cells and stroma through the induction of epithelial-mesenchymal transition (EMT). This study aimed to clarify the prognostic value of evaluating primary tumor histology with the anatomical extent of disease in patients with colorectal liver metastasis (CRLM).</p><p>Methods: Prognostic analyses were performed in 411 CRLM patients who underwent hepatectomy at two institutions. Tumors were graded into one of three histological categories based on integrated assessment of EMT-associated histology (HistologyEMT) in primary tumors, i.e., poorly differentiated clusters (PDCs) and desmoplastic reaction (DR). </p><p>Results: A prognostic grouping system for the anatomical extent of disease (N stage, liver metastasis number and size, and extrahepatic disease; Gradeanatomical) stratified patients into three groups with different five-year relapse-free survival (RFS) rates after hepatectomy: A, 31% (191 patients); B, 15% (124 patients); and C, 6% (96 patients; P < 0.0001). HistologyEMT (A, G1 PDC and mature-type DR; C, G3 PDC and immature-type DR; and B, others) identified 49, 120, and 242 patients with 46%, 5%, and 22% five-year RFS, respectively (P < 0.0001). Among prognostic factors, the Akaike information criterion was most favorable in Gradeanatomical, followed by HistologyEMT. Multivariate analysis demonstrated that these two factors independently impacted RFS; two-year RFS after hepatectomy in different patient groups had a wide range (10%-76%).</p><p>Conclusions: Histological assessment of dedifferentiation and the stromal environment of primary tumors contributed to effective risk stratification of early relapse after hepatectomy, which could be useful to determine clinical management for CRLM patients.</p>
Journal
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- JMA Journal
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JMA Journal 3 (3), 240-250, 2020-07-15
Japan Medical Association / The Japanese Associaiton of Medical Sciences
