Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review
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Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases.
A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising ≥5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike’s information criterion (AIC).
PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 µm submucosal invasion and 1307 (43.2 %) with ≥1000 µm submucosal invasion (P < 0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P < 0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P < 0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48).
PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases.
KeywordsT1 colorectal cancer Endoscopic excision Poorly differentiated clusters Tumor budding Lymph node metastases
Lymph node metastasis
Poorly differentiated cluster
Akaike’s information criterion
Japanese Society for Cancer of the Colon and Rectum
Hematoxylin and eosin
The authors thank Professor Hidetaka Mochizuki who served as President of the 75th meeting of the Japanese Society for Cancer of the Colon and Rectum (JSCCR) for his valuable advice on this study. The authors also thank following investigators who participated in this study by offering their institutional data: Keisuke Minamimura (Mitsui Memorial Hospital), Munenori Ide (Gunma University), Yoshikazu Koide (Fujita Health University School of Medicine), Fumio Konishi (Saitama Medical Center, Jichi Medical University), Hiroshi Iino (Yamanashi Medical University), Soichi Tanaka (Matsuda Hospital Colo-proctological Institute), Mitsuo Kishimoto (Kyoto Prefectural University of Medicine), Tadahiko Masaki (Kyorin University School of Medicine), Keizo Yamaguchi (Kurume University Medical Center), Shinji Tanaka and Koichi Nakadoi (Hiroshima University Hospital), Hideto Fujita (Kanazawa University Hospital), Shiro Adachi and Taishi Hata (Toyonaka Municipal Hospital), Sachio Yokoyama (Kumamoto City Hospital), Shingo Kameoka and Takuzo Hashimoto (Tokyo Women’s Medical University), Yusuke Kinugasa (Shizuoka Cancer Center Hospital), Hiroyoshi Takemoto (Sakai Municipal Hospital), Takeyasu Suda (The Nippon Dental University Medical Hospital), Koji Nagata (Saitama Medical University).
Conflict of interest
The authors declare that they have no conflict of interest.
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