title: Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.
abstract: The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.
authors.affiliation: Departments of *Surgery ‡Laboratory Medicine ##Laboratory for Mathematics, National Defense Medical College, Saitama †Department of Surgery, Teikyo University School of Medicine ∥Department of Surgery, International Medical Center of Japan ¶Department of Surgery, Kyorin University School of Medicine §§Department of Surgery II, Tokyo Women's Medical University ***Department of Surgery, Tokyo Medical and Dental University, Tokyo §Department of Surgery, Coloproctology Center, Takano Hospital, Kumamoto #Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata **Division of Gastrointestinal Surgery, Shizuoka Cancer Center Hospital, Shizuoka ††First Department of Surgery, University of Yamanashi, Yamanashi ‡‡Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto ∥∥Department of Surgical Oncology, Colorectal and Pelvic Surgery Division, National Cancer Center Hospital East, Chiba ¶¶Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Ohki
authors.initials: O
authors.lastname: Miyake
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Masaki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kinugasa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mori
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Kameoka
authors.forename: Yu
authors.initials: Y
authors.lastname: Sato
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakadoi
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult