Recently, colorectal cancer (CRC) has become a worldwide health issue in both morbidity and mortality. In Western societies, CRC is the third most common cancer [1,2], and in Asia, CRC morbidity is increasing [3,4]. CRC is a heterogeneous type of cancer, meaning that a variety of different histology types, including adenocarcinomas (ADCs), adenosquamous carcinomas, spindle cell carcinomas, squamous cell carcinomas, and undifferentiated carcinomas, are possible [5]. According to its histologic type, CRC has different clinical features; thus, identifying the characteristics of each CRC subtype is an important step in managing the treatment of patients with CRC appropriately.

Among these pathologic subtypes, signet-ring-cell carcinomas (SRCCs) of the colon and of the rectum are rare histologic subtypes of colorectal ADCs and account for only approximately 0.5%–1% and 15%–20% of all ADCs, respectively [6]. By definition, a 50% or greater signet-ring-cell component is required for a colorectal carcinoma to be designated as a signet-ring-cell colorectal carcinoma [7,8]. Because many patients with a SRCC are diagnosed at more advanced stages and in an unresectable state, the prognosis for such a patient is generally poorer than that for a patient with a colorectal non-mucinous ADC [9,10,11,12]. According to previous studies, a specific histological type of colorectal carcinoma such as a SRCC has a poorer prognosis [13,14,15], but the results in previous studies cannot be readily and widely accepted because of their limitations, such as their small sample size and the lack of propensity matching in the study's design.

Until now, not many studies have used propensity score matching to determine the prognostic significance of a SRCC. In this research, we attempt to identify whether or not the poor prognosis associated with patients with SRCCs is due to the histologic type being a signet-ring-cell type itself or is a secondary outcome due to the cancer's advanced stage. A further aim of this study is to evaluate the relationship between the clinicopathologic features of SRCCs and the prognosis for patients with a SRCC and to compare any identified relationship to the corresponding known relationships for patients with colorectal ADCs.

A SRCC of the colorectum was first reported in 1951 [16]. It is a rare and distinctive type of cancer [6], and its prognosis is poorer than the prognoses for other types. It usually presents at more advanced stages because its clinical symptoms develop late [9]. Bonello et al. [17] reported that this delay in diagnosis was due to its rarity and intramucosal tumor spread with relative sparing of the mucosa.

In some studies [18,19], researchers used univariate analyses to report that a lower TNM stage and the absence of lymphovascular invasion had favorable effects on the survival rates of patients with a SRCC. Decreased invasion depth and no lymph-node metastasis also had favorable effects on survival in patients with a SRCC and patients with an ADC. Moreover, Sung et al. [14] reported that the absence of lymphatic invasion had a favorable outcome on OS compared to previous studies. In other previous studies, mucinous histologic type was an independent poor prognostic factor in some studies [20,21], but not in others [22,23,24]. Wu et al. [22] suggested that the different DFS and OS rates could be associated with differences in the stage upon presentation rather than the cancer's pathologic subtype.

In our research, we found that in patients with a resectable, nonhereditary, primary colorectal SRCC, the DFS and the OS rates were significantly lower in the SRCC group compared to the ADC group before propensity score matching, and the results were the same after propensity score matching. In a subgroup analysis stratified by stage after propensity score matching, the SRCC histologic type could be regarded as an independent poor prognostic factor when the cancer was in an advanced stage although no significant differences in DFS and OS were found between the SRCC and the ADC groups when the cancer was in an early stage. We might explain the poor prognosis for patients with a SRCC by the aggressiveness of its infiltrating growth because of the higher rate of lymphovascular invasion; in addition, slow infiltration without penetrating the mucosa layer could be the reason for its late diagnosis, meaning that SRCC could be diagnosed at a more advanced stage [5,8,10,11,12].

Our study has several limitations. First, we collected patient data from a single comprehensive cancer center. Considering the Korean medical environment, patients with a higher social economic status and a more advanced disease usually go to tertiary medical centers. This means that selection bias must be considered and that our results may not be generalizable to all patients with signet-ring-cell colon cancer. Second, this is not a prospective cohort; therefore, the treatment strategy was selected according to the surgeon's preference and choice and so was not controlled. Third, its statistical power is limited due to the rarity of SRCC. However, the number of SRCC patients was maintained as 71 before and after propensity score matching; thus, we could maintain statistical power quiet well. We collected patient data from a single cancer center, but we could collect relatively many SRCC patient data and exclude the surgical technique's influence on DFS and OS because the Samsung Medical Center is a comprehensive cancer center.

In conclusion, SRCC is an uncommon and rare subtype of CRC that shows poor OS and DFS rates compared to other histologic types such as a classical ADC. In many other studies, SRCC is frequently diagnosed at a more advanced stage and with more aggressive pathologic features, such as lymphovascular or neural invasion, which eventually translates to poor survival [8,22]; however, in our study, we could regard SRCC as the single prognostic factor of CRC. Therefore, more intensive surveillance and closer follow-up should be afforded to patients with SRCC, despite the condition's relatively rarity.