Hideki Ueno1, Shigeki Sekine2, Taihei Oshiro3, Yukihide Kanemitsu3, Tetsuya Hamaguchi4, Dai Shida3, Atsuo Takashima4, Megumi Ishiguro5, Eisaku Ito6, Yojiro Hashiguchi7, Fukuo Kondo8, Hideyuki Shimazaki9, Satsuki Mochizuki10, Yoshiki Kajiwara10, Eiji Shinto10, Junji Yamamoto10, Yasuhiro Shimada4. 1. Department of Surgery, National Defense Medical College, Saitama. Electronic address: ueno_surg1@ndmc.ac.jp. 2. Molecular Pathology Division, National Cancer Center Research Institute, Tokyo. 3. Colorectal Surgery Division, National Cancer Center Central Hospital, Tokyo. 4. Gastrointestinal Medical Oncology Division, National Cancer Center Central Hospital, Tokyo. 5. Department of Translational Oncology, Tokyo Medical and Dental University, Tokyo. 6. Department of Pathology, Tokyo Medical and Dental University, Tokyo. 7. Department of Surgery, Teikyo University School of Medicine, Tokyo. 8. Department of Pathology, Teikyo University Hospital, Tokyo. 9. Department of Laboratory Medicine, National Defense Medical College, Saitama. 10. Department of Surgery, National Defense Medical College, Saitama.
Abstract
BACKGROUND: Growing evidence suggests the importance of stroma in determining cancer biology and recent studies have identified that genes closely associated with poor prognosis subtypes of colorectal cancer are expressed by the stroma rather than epithelial cancer cells. We aimed to clarify the prognostic value of the novel histologic classification of desmoplastic reaction in stage III colorectal cancer. METHODS: A pathologic review was conducted for 466 stage III colorectal cancer patients in a single Japanese institution (1999-2006). Desmoplastic reaction was classified as mature, intermediate, or immature according to existence of hyalinized collagen bundles and myxoid stroma, both appear exclusively at the desmoplastic front. An additional 432 patients treated at four independent institutions (2007-2008) were examined as a second cohort to validate the results. RESULTS: According to desmoplastic reaction, 164, 133, and 169 patients were classified as mature, intermediate, and immature, respectively. Five-year relapse-free survival rates were highest in the mature group (86.0%), followed by the intermediate (73.7%) and immature (50.9%) groups. An adverse prognostic impact of desmoplastic reaction was invariably observed in stage IIIB, which contained 71% of stage III cases. Harrell's concordance index for relapse-free survival was greater in desmoplastic reaction (0.66) than any conventional tumor-associated prognostic factors including tumor node metastasis substage (0.62) and tumor grade (0.53). Similar results were observed in the second cohort, wherein desmoplastic reaction categorization was the most influential prognostic factor. CONCLUSION: Histologic desmoplastic reaction categorization could be a key to solve the issue of prognostic heterogeneity in stage III colorectal cancer, thereby enhancing the value of tumor node metastasis stage.
BACKGROUND: Growing evidence suggests the importance of stroma in determining cancer biology and recent studies have identified that genes closely associated with poor prognosis subtypes of colorectal cancer are expressed by the stroma rather than epithelial cancer cells. We aimed to clarify the prognostic value of the novel histologic classification of desmoplastic reaction in stage III colorectal cancer. METHODS: A pathologic review was conducted for 466 stage III colorectal cancerpatients in a single Japanese institution (1999-2006). Desmoplastic reaction was classified as mature, intermediate, or immature according to existence of hyalinized collagen bundles and myxoid stroma, both appear exclusively at the desmoplastic front. An additional 432 patients treated at four independent institutions (2007-2008) were examined as a second cohort to validate the results. RESULTS: According to desmoplastic reaction, 164, 133, and 169 patients were classified as mature, intermediate, and immature, respectively. Five-year relapse-free survival rates were highest in the mature group (86.0%), followed by the intermediate (73.7%) and immature (50.9%) groups. An adverse prognostic impact of desmoplastic reaction was invariably observed in stage IIIB, which contained 71% of stage III cases. Harrell's concordance index for relapse-free survival was greater in desmoplastic reaction (0.66) than any conventional tumor-associated prognostic factors including tumor node metastasis substage (0.62) and tumor grade (0.53). Similar results were observed in the second cohort, wherein desmoplastic reaction categorization was the most influential prognostic factor. CONCLUSION: Histologic desmoplastic reaction categorization could be a key to solve the issue of prognostic heterogeneity in stage III colorectal cancer, thereby enhancing the value of tumor node metastasis stage.
Authors: Marloes Smit; Gabi van Pelt; Annet Roodvoets; Elma Meershoek-Klein Kranenbarg; Hein Putter; Rob Tollenaar; J Han van Krieken; Wilma Mesker Journal: JMIR Res Protoc Date: 2019-06-14
Authors: Naohiko Akimoto; Juha P Väyrynen; Melissa Zhao; Tomotaka Ugai; Kenji Fujiyoshi; Jennifer Borowsky; Rong Zhong; Koichiro Haruki; Kota Arima; Mai Chan Lau; Junko Kishikawa; Tyler S Twombly; Yasutoshi Takashima; Mingyang Song; Xuehong Zhang; Kana Wu; Andrew T Chan; Jeffrey A Meyerhardt; Marios Giannakis; Jonathan A Nowak; Shuji Ogino Journal: Front Immunol Date: 2022-03-22 Impact factor: 7.561