Objective: To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis. Methods: The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result: Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III-IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ2=6.293,P=0.043). The proportions of TNM Stage III-IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ2=13.994,P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ2=10.457,P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ2=5.086,P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ2=19.791,P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ2=4.601,P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ2=11.996,P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ2=7.643, P=0.006), had a higher proportion of TNM Stage III-IV disease (60.2% [100/166] vs. 24.2% [8/33], χ2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively (P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS (P=0.026). Conclusions: Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.
目的： 探讨散发性同时性多原发结直肠癌（SSCRC）多个癌灶相对位置及微卫星状态对于临床病理特征及预后的影响。 方法： 回顾性收集自2008年1月至2022年7月期间，于浙江省肿瘤医院结直肠外科收治的278例SSCRC患者的临床病理及随访资料。按照多个癌灶的相对位置，将患者分为3组，分别是：（1）右半组（多个癌灶均分布于盲肠、升结肠、结肠肝曲、横结肠）；（2）左半组（多个癌灶均分布于结肠脾曲，降结肠，乙状结肠、直肠）；（3）左半+右半组（多个癌灶在右半结肠和左半结肠/直肠均有分布）。按照微卫星状态（MSI），将患者分为两组，分别是：MSI-H组（错配修复缺陷）和MSI-L+MSS组（错配修复完整）。比较组间的临床特征和预后差异。不同临床特征的比较采用χ2检验，预后比较采用Kaplan-Meier生存分析和Log-rank检验。 结果： 278例SSCRC患者中，有256例（92.1%）癌灶数量为2个，22例（7.9%）>2个；255例（91.7%）病灶病理表现为腺癌，23例（8.3%）病灶包含或表现为黏液腺癌；136例（48.9%）发生淋巴结转移；癌灶浸润深度超过肌层的患者238例（85.6%）；TNM分期为Ⅲ或Ⅳ期者147例（52.9%）；左半组、右半组以及左半+右半组分别有155例（55.8%）、55例（19.8%）和68例（24.5%）。全组有199例行完整4项错配修复蛋白的免疫组化检查，其中有166例微卫星状态为MSI-L+MSS；33例微卫星状态为MSI-H。左半组、左半+右半组以及右半组比较，女性比例分别占16.8%（26/155）、26.5%（18/68）和49.1%（27/55），差异有统计学意义（χ2=22.335，P<0.001）；癌灶数量≥3个的比例分别占5.2%（8/155）、16.2%（11/68）和5.5%（3/55），差异有统计学意义（χ2=8.438，P=0.015）；黏液腺癌的比例分别占4.5%（7/155）、8.8%（6/68）和18.2%（10/55），差异有统计学意义（χ2=10.026，P=0.007）；淋巴结转移比例分别占55.5%（86/155）、48.5%（33/68）和30.9%（17/55），差异有统计学意义（χ2=9.817，P=0.007）；浸润T3~4分期比例分别占81.3%（126/155）、88.2%（60/68）、94.5%（52/55），差异有统计学意义（χ2=6.293，P=0.043）；肿瘤TNM临床分期Ⅲ~Ⅳ的比例分别占59.4%（92/155）、54.4%（37/68）和32.7%（18/55），差异有统计学意义（χ2=11.637，P=0.003）。3组在年龄、癌灶大小、远处转移、合并腺瘤、神经侵犯以及脉管侵犯等方面差异均无统计学意义（均P>0.05）。相较于MSI-H，MSI-L+MSS患者年龄>65岁和男性的比例更高［分别为50.6%（84/166）比15.2%（5/33），χ2=13.994，P<0.001；80.7%（134/166）比54.5%（18/33），χ2=10.457，P=0.001］，更易发生于左半［63.3%（105/166）比24.2%（8/33），χ2=18.232，P<0.001］，癌灶长径<4 cm比例较高［54.8%（91/166）比33.3%（11/33），χ2=5.086，P=0.024］，黏液腺癌比例偏低［4.2%（7/166）比27.3%（9/33），χ2=19.791，P<0.001］，更容易发生远处转移［22.3%（37/166）比6.1%（2/33），χ2=4.601，P=0.032］、淋巴结转移［57.2%（95/166）比24.2%（8/33），χ2=11.996，P<0.001］和神经侵犯［28.9%（48/166）比6.1%（2/33），χ2=7.643，P=0.006］，TNM分期为Ⅲ~Ⅳ期比例更高［60.2%（100/166）比24.2%（8/33），χ2=14.374，P<0.001］，而肿瘤家族史比例偏低［28.9%（48/166）比60.6%（20/33），χ2=12.228，P<0.001］，差异均有统计学意义（均P<0.05）。两者在癌灶数量、浸润深度、是否合并腺瘤以及脉管癌栓方面的差异均无统计学意义（均P>0.05）。在33例MSI-H患者的错配修复蛋白缺失情况中，以PMS-2的缺失频率最高，为66.7%（22/33），MLH-1次之，为57.6%（19/33），而MSH-2和MSH-6缺失的比例相对较少，分别为33.3%（11/33）和24.2%（8/33）。Kaplan-Meier生存分析和Log-rank检验显示：不同癌灶相对位置分组中，右半组、左半+右半组、左半组的3年总生存率分别为96.8%、79.6%以及88.5%，差异有统计学意义（P=0.021）；不同微卫星状态分组中，MSI-H的3年总生存率为93.8%，较MSI-L+MSS的78.4%更优，差异有统计学意义（P=0.026）。 结论： 在散发性同时性多原发结直肠癌中，以右半组局部浸润深度最深，以左半组淋巴结转移能力最强，临床TNM分期最晚，MSI-H占比最低，预后最差。.