Ueno Hideki, Kanemitsu Yukihide, Sekine Shigeki, Ishiguro Megumi, Ito Eisaku, Hashiguchi Yojiro, Kondo Fukuo, Shimazaki Hideyuki, Mochizuki Satsuki, Kajiwara Yoshiki, Shinto Eiji, Yamamoto Junji
Departments of *Surgery **Laboratory Medicine, National Defense Medical College, Saitama Departments of †Colorectal Surgery Division, National Cancer Center Hospital ‡Molecular Pathology Division, National Cancer Center Research Institute §Department of Colorectal Surgery, Tokyo Medical and Dental University Medical Hospital ∥Department of Pathology, Tokyo Medical and Dental University ¶Department of Surgery, Teikyo University School of Medicine #Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
Am J Surg Pathol. 2017 Nov;41(11):1506-1512. doi: 10.1097/PAS.0000000000000946.
Although recent findings of cancer biology research indicate that prognostic power arises from genes expressed by stromal cells rather than epithelial cells, desmoplastic reaction (DR) has not been completely examined as a prognostic marker for colorectal cancer. A pathologic review of 821 stage II and III patients who underwent R0 resection for colorectal cancer at 4 independent institutions was conducted. DR was classified as mature, intermediate, or immature based on the existence of hyalinized keloid-like collagen and myxoid stroma at the extramural desmoplastic front. Totally, 325, 282, and 214 patients were classified as having mature, intermediate, and immature DR, respectively. DR significantly influenced the recurrence rate in the liver, lung, and peritoneum (P≤0.0001 to 0.01). Five-year relapse-free survival (RFS) rate was the highest in the mature group (85.7%), followed by the intermediate (77.3%) and immature (50.4%) groups. A significant adverse impact of immature stroma on RFS was observed in subset analyses of the 4 institutions. Multivariate analysis revealed that DR, along with T and N stages, is an independent prognostic factor. On the basis of Harrell's concordance index, the prognostic power of DR categorization (0.67) in stratifying RFS was greater than any other conventional prognostic factors, including TNM (0.64), N (0.62) and T stages (0.59), venous invasion (0.59), and tumor grade (0.54). Characterizing DR based on the histologic products of activated fibroblasts is valuable for evaluating prognostic outcomes. To our knowledge, this is the first study reporting a greater prognostic power of histology of the fibrotic stroma than that of tumor factors.
尽管癌症生物学研究的最新发现表明，预后能力源自基质细胞而非上皮细胞所表达的基因，但促结缔组织增生性反应（DR）作为结直肠癌的预后标志物尚未得到充分研究。我们对4家独立机构中821例接受结直肠癌R0切除的II期和III期患者进行了病理回顾。根据壁外促结缔组织增生前沿透明样瘢痕疙瘩样胶原和黏液样基质的存在情况，将DR分为成熟型、中间型或未成熟型。总共有325例、282例和214例患者分别被归类为具有成熟型、中间型和未成熟型DR。DR对肝、肺和腹膜的复发率有显著影响（P≤0.0001至0.01）。成熟组的5年无复发生存率（RFS）最高（85.7%），其次是中间型（77.3%）和未成熟型（50.4%）组。在4家机构的亚组分析中，观察到未成熟基质对RFS有显著的不利影响。多变量分析显示，DR与T和N分期一样，是一个独立的预后因素。根据哈雷尔一致性指数，DR分类在分层RFS方面的预后能力（0.67）大于任何其他传统预后因素，包括TNM（0.64）、N（0.62）和T分期（0.59）、静脉侵犯（0.59）以及肿瘤分级（0.54）。基于活化成纤维细胞的组织学产物来表征DR，对于评估预后结果具有重要价值。据我们所知，这是第一项报道纤维化基质组织学比肿瘤因素具有更强预后能力的研究。
