It is difficult to determine the clinicopathologic characteristics and long-term outcome of stage I MAC. Even though the long-term survival of stage I CRC is thought to be much better, it is still unclear whether mucinous histology had significant prognostic effect on stage I CRC. Previous research shows poor survival for CRC patients with a higher mucinous content [17, 18], but there were also reports with opposite conclusions [19, 20]. Here, we analyzed the prognostic value of MAC focusing on stage I CRC and correlated the mucinous histology with clinical and pathological features of stage I CRC. Compared with non-MAC patients, MAC had more T2 patients in stage I at presentation, more colon cancers and a higher MSI status. Many independent risk factors for recurrence and long-term survival were found in our study, including abnormal CEA level, LVI and MSS phenotypes. However, there was no correlation between mucinous histology and survival in stage I CRC.
In our study, univariate and multivariate analyses showed that that the histology pattern of MAC was not a prognostic factor for DFS or OS. Although the pathological T2-classification of MAC was higher in stage I patients than in non-MAC patients (87.5% vs 64.9%, p = 0.001), distinct clinical results were not observed. Du et al. [21] also reported that patients with MAC in stage III alone shown poorer DFS and OS compared with the non-MAC group, which means the worse survival of MAC patients might be due to regional lymph node metastasis.
Serum CEA is the most widely used tumor markers for diagnosis and recurrence monitoring of CRC. Several studies have investigated the ability of CEA to predict tumor recurrence and metastasis [22–24]. However, in stage I CRCs, there has been a paucity of evidence for it being a predictive factor for recurrence. Here, we found abnormal pretreatment CEA was an independent risk factor for recurrence even in stage I CRC. It suggests that if the serum CEA level is high preoperative in patients, the recurrence of CRC should be closely monitored, even in stage I CRC.
LVI is considered to be an early event in lymph node metastasis, and it has been proved to be an independent predictor of survival in CRC. The LVI group showed a higher risk of recurrence and a significantly lower overall survival rate in advanced CRC compared with the non-LVI group[25]. Meanwhile, LVI also has an independent predictor power for poor prognosis rectal cancer after neoadjuvant therapy and surgery [26]. However, the prognostic value of LVI in stage I CRC patient has not been well studied. Our study confirms that LVI is an important risk factor for stage I CRC recurrence. This suggests that LVI might be a sensitive marker for local recurrence and distant metastasis, even the patients without LN metastases.
The effect of MSI on the prognosis of CRC is controversial. MSI status influences the prognosis of CRC only in specific stages [27, 28]. Compared to MSS patients, MSI patients were found to possess worse survival in stage III colon cancer [29]. While opposite conclusion was found that MSI status was related to a better survival in stage II CRC [30]. Our study revealed that stage I CRC patients with MSI status showed a much better survival compared with the MSS group. MSI tumors were also found significantly associated with mucinous histology in stage I CRC patients, suggesting patients of MC are suitable for immunotherapy when recurrence and metastasis occur in the future.