The study is a single center study, 5753 patients were analyzed retrospectively, all of them have undergone radical resections due to CRC by specialist surgern in the Sixth Affiliated Hospital between January 2011 to May 2016. . The following exclusion criteria were applied: patients with familial adenomatous polyposis (FAP), hereditary non-polyposis CRC (HNPCC); patients with synchronous or metachronous cancer; death due to non-cancer causes such as heart disease and cerebral infarction; patients underwent local excision or neoadjuvant therapy were also excluded. Among them, 542 patients (9.42%) were diagnosed as stage I CRC on histopathologic examination and met the criteria for enrollment. Of the 542 patients, 12 patients lost to follow-up, and 27 patients died from non-cancer causes. Therefore, 503 patients were analyzed in this study.
Clinicopathologic evaluation
Before surgery, patients underwent a baseline assessment of demographics and disease characteristics, blood carcinoembryonic antigen (CEA) tests, and tumor imaging. At least two pathologists, who are specialized in CRC, assessed the surgical specimens. Among the 503 patients, 56 were defined as MAC when the tumor mass consisted 50% or more of mucin ingredient, mostly extracellular; and the other tumors were defined as non-MAC. Hematoxylin and eosin staining was used to assess lymph nodes metastasis and lymphovascular invasion (LVI). Immunohistochemically (IHC) assessment of mismatch repair (MMR) genes in tissue samples were performed as described by Förster et al. [14]. The clinicopathological features of all 503 patients are shown in Table 1. All patients were staged by TNM classification criteria [15].
Table 1. The relationship between clinicopathological characteristics and mucinous adenocarcinoma in stage I colorectal cancer
Variable
|
MAC
(n=56)
|
non-MAC
(n = 447)
|
p value
|
|
Sex
|
|
|
|
|
Male
|
33(58.9%)
|
243(54.3%)
|
0.518
|
|
Female
|
23(41.1%)
|
204(45.6%)
|
|
|
Age
|
|
|
|
|
≤ 65
|
39(69.6%)
|
278(62.2%)
|
0.277
|
|
> 65
|
17(30.4%)
|
169(37.8%)
|
|
|
Preoperative CEA
|
|
|
|
≤5 ng/dL
|
51(91.1%)
|
390(87.2%)
|
0.413
|
|
> 5 ng/dL
|
5(8.9%)
|
57(12.8%)
|
|
|
T classification
|
|
|
|
1
|
7(12.5%)
|
157(35.1%)
|
0.001*
|
|
2
|
49(87.5%)
|
290(64.9%)
|
|
|
Location
|
|
|
|
|
Colon
|
24(42.9%)
|
133(29.7%)
|
0.046*
|
|
Rectal
|
32(57.1%)
|
314(70.3%)
|
|
|
Size
|
|
|
|
|
<3cm
|
27(48.2%)
|
266(59.5%)
|
0.107
|
|
≥3cm
|
29(51.8%)
|
181(40.5%)
|
|
|
LVI
|
|
|
|
|
(–)
|
52(92.8%)
|
435(97.3%)
|
0.073
|
|
(+)
|
4(7.2%)
|
12(2.7%)
|
|
|
Less than 12 lymph nodes
|
|
|
|
|
Yes
|
9(16.1%)
|
82(18.3%)
|
0.678
|
|
No
|
47(83.9%)
|
365(81.7%)
|
|
|
MSI
|
|
|
|
|
Yes
|
5(8.9%)
|
13(2.9%)
|
0.023*
|
|
No
|
51(91.1%)
|
433(97.1%)
|
|
|
MAC: mucinous adenocarcinomas
CEA : carcinoembryonic antigen
MSI : microsatellite instability
Treatment
All patients underwent radical surgery. Colon cancer is completely removed by mesocolic excision with Lymph node (LN) dissection at R0-resection level. Resection of rectal cancer were performed by total mesorectal excision as described [16]. Recurrence occurred in 68 of 503 patients during follow-up and 25 patients underwent re-radical surgery. Laparoscopic surgery is performed for most patients.
Data collection
The follow-up information of 503 patients was collect and analyzed. The median follow-up period of all cases was 59 months (2 to 103 months). According to the mucinous histology, patients were divided into two groups: the MAC group and the non-MAC group. Clinicopathologic factors (age, sex, preoperative CEA lever, tumor location, tumor size, T stage, histologic subtype, the number of obtained lymph nodes, LVI, MSI status) were analyzed. We selected the 5-year disease-free survival (DFS) as the primary endpoint, which defined as the time from the date of radical resection to the diagnosis of cancer recurrence. The 5-year overall survival rate (OS) was selected as the second endpoint, defined as the time from the date of radical resection to death caused by cancer.
Statistical analysis
The associations between the discrete variables were analyzed by Spearman rank correlation test. p value <0.05 was regarded as statistically significant. Univariate analyses were performed by χ2 tests to evaluate the associations between clinical variables and the tumor histology. The survival probability was analyzed by Kaplan–Meier procedure, and the distribution differences were assessed by the log-rank test. Clinicopathologic factors such as age, sex, preoperative CEA lever, tumor location, tumor size, T stage, histologic subtype, the number of obtained lymph nodes, LVI, MSI status were analyzed. In multivariate analysis, cox proportional risk model (HR) was also used to evaluate the predictive value of various factors. The statistical analysis was carried out by using IBM SPSS ver. 20.0(IBM, Armonk, NY, USA).