Park Hye Eun, Yoo Seungyeon, Bae Jeong Mo, Jeong Seorin, Cho Nam-Yun, Kang Gyeong Hoon
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
J Pathol Transl Med. 2018 Nov;52(6):386-395. doi: 10.4132/jptm.2018.10.02. Epub 2018 Nov 14.
Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance.
Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC.
SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151).
Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.
既往关于同时性结直肠癌（SCRC）的研究报告了其临床病理、分子特征及预后意义方面不一致的结果。
选取46例未接受新辅助化疗和/或放疗且与家族性腺瘤性息肉病无关的多发进展期肿瘤（T2或更高分期）患者，对其99个肿瘤进行临床病理和分子分析。考虑到SCRC患者所行手术类型的分布情况以及SCRC单个肿瘤的T分期，选取92例孤立性结直肠癌（CRC）作为对照。
与孤立性CRC相比，多发进展期肿瘤的SCRC与更频繁的淋巴结转移（p = 0.003）和远处转移（p = 0.001）显著相关。SCRC组和孤立性CRC组之间KRAS突变、微卫星不稳定性及CpG岛甲基化表型状态无差异。在单因素生存分析中，即使校正手术范围、辅助化疗或分期后，SCRC患者的总生存和无复发生存仍显著低于孤立性CRC患者。多因素Cox回归分析显示，肿瘤多灶性是总生存的独立预后因素（风险比，4.618；95%置信区间，2.126至10.030；p < 0.001），但不是无复发生存的独立预后因素（p = 0.151）。
研究结果提示，进展期T分期肿瘤的多灶性可能与淋巴结转移风险增加及生存不良风险因素相关，这引发了对美国癌症联合委员会肿瘤-淋巴结-转移分期指南的关注，该指南中索引肿瘤的T分期决定SCRC的T分期。
