Lauren classification is widely used in scientific research, but there are still different opinions on this method. One reason is that the sample size is too small, with most of the cases included in the study range from several hundred to thousand, Therefore, there is no substantial progress owing to the less representativeness of these research results. Although Li et al. recently reported a study of Lauren classification in early GC based on the SEER database , they included 5593 cases and only focused on early GC. In our study, we have a lot of data available with 28000 patients, so we can get the desired and more reliable results theoretically.
Analysis of the clinicopathological features showed that the age of onset of intestinal-type GC was older (≥ 65) (P < 0.001) than that of diffuse-type GC; additionally, when comparing intestinal-type GC with diffuse-type GC, there were more males affected than females (P < 0.001), there was a higher degree of pathological differentiation (P < 0.001), disease occurred at an earlier stage (P < 0.001), disease was more likely to be distributed in the lower stomach (P < 0.001), tumour size was more likely to be 4–8 cm (P < 0.001), there was more invasion into the muscularis propria (P < 0.001), there was less lymph node metastasis (P < 0.001), and there was less distant metastasis (P < 0.001). Compared with diffuse-type, the prognosis of intestinal-type was significantly better. Different from intestinal-type group, patients in diffuse-type group have relatively poor pathological differentiation (P < 0.001), and diffuse cases were often at an advanced stage when they were diagnosed, to be located in the upper stomach, and to have distant metastasis (P < 0.001) compared with intestinal cases.
LNM is often considered an important determinant of outcomes and treatment strategy choices in EGC [12–13]. While many studies have reported a high rate of diffuse lymph node metastasis, our study concluded that two groups didn’t significantly differed in lymph node metastasis; Thus, the LNM risk of intestinal and diffuse GC is considered similar. Our findings indicated that there was no positive correlation between LNM and Lauren type (OR = 1.096; 95% CI: 0.856–1.403; P = 0.467), but we demonstrated that the hazard of intestinal lymph node metastasis in all stages of GC was higher than that in the diffuse type (OR = 0.891; 95% CI, 0.801–0.992; P = 0.036).
The cause of these contradictory results may be the fact that the patients who basically register the information in the SEER database are mainly postoperative pathology. Moreover, the general surgery patients were mainly without metastasis and peripheral lymph node metastasis, while the proportion of distant metastasis in the surgical enrollment group was relatively small. In this study, the proportion of patients with intestinal type GC undergoing surgery was 68.07%, and the proportion of patients with diffuse GC undergoing surgery was 44.87%. As a result, we obtained this result when we estimated the risk of lymph node metastasis. However, theconclusion of this large sample of studies also remind us that we should pay more attention to lymphatic metastasis of intestinal type GC than before.
Another reason may be that our definitions of intestinal and diffuse types differ from those of other studies. In addition to Lauren classification, we also used WHO classification. Intestinal GC also includes papillary adenocarcinoma, highly differentiated/moderately differentiated tubular adenocarcinoma, diffuse GC including signet-ring cell carcinoma, and low-differentiated adenocarcinoma. Different inclusion criteria may have resulted in inconsistent analysis results. Based on the conclusion that the hazard of lymph node metastasis in intestinal-type GC is high, clinicians must be cautious when choosing surgical treatment for intestinal-type GC.
The most obvious finding to emerge from the analysis is that the prognosis of diffuse-type GC was worse than that of intestinal-type GC. The median DSS time of intestinal-type patients was 29.79 months, compared with 10.41 months in diffuse-type patients, and the 5-year survival DSS rate was 42.8% and 21.4%, respectively. These findings are consistent with previous reports  and may be partially explained by the tendency of the diffuse-type to present at more advanced T and N stages.
Previous research findings related to GC are inconsistent and contradictory with our results, and the studies have showed that the prognosis of intestinal-type GC is worse than that of diffuse-type GC. In particular, studies by Li et.al , which are based on the SEER database, analysed only early GC patients. The results showed that patients of different GC subtypes had similar prognoses, or even that the prognosis of intestinal-type GC was worse than that of diffuse-type GC. Therefore, we further analysed the differences in prognosis between patients with early-stage GC and diffuse-type GC. it was concluded that the prognosis of diffuse-type GC was worse than that of intestinal-type GC in both early stage and all-stage GC populations.
Most studies have concluded that intestinal-type GC is common in older men, has a low degree of invasion, has a high level of lymph node metastases, and has vascular invasion . Diffuse GC is common in young and female patients and has serous invasion; additionally, lymph node metastasis occurs very early [ 16–19].
In intestinal-type GC, the median DSS time decreased according to tumour infiltration depth (T1, T2, T3, and T4), indicating that an increase in tumour infiltration depth was negatively correlated with the prognosis of patients. Analysis of lymph node metastasis revealed that patient survival time decreased with the increase of the number of lymph node metastasis. The survival time of patients with distant metastases was evidently shorter than that of patients without distant metastases. The relationship between tumour invasion depth, lymph node metastasis, distant metastasis and prognosis in diffuse GC also showed the same trends. Studies have shown that lymph node metastasis is an independent factor in the prognosis of patients [20–21]. Patients with node-negative disease have a higher 5-year survival rate than that of patients with lymph node metastasis, and the survival time of patients with lymph node metastasis decreases with an increase in the number of metastatic lymph nodes. The larger extent of metastasis from lymph nodes in diffuse GC than intestinal GC suggests that the prognosis of diffuse GC is worse than that of intestinal-type GC. Invasive depth of diffuse patients
The proportion of GC patients with T3 and T4 disease in diffuse-type is higher than that in intestinal-type. Previous researches have shown that the depth of invasion is an independent factor in the prognosis of GC [22–24]. According to our study, the prognosis of diffuse GC is worse than that of intestinal-type GC. In patients with diffuse TNM, the proportion of patients with stage I and II disease was lower than that of patients with intestinal-type disease (P = 0.004), while the percentage of patients with stage IV was significantly higher than that of patients with intestinal-type disease (P = 0.008). Previous studies have shown that patients with stage III and IV GC have poor prognosis, and the 5-year survival rate is significantly lower in these patients than in patients with stage I and II disease [25–26]. The prognosis of diffuse GC is worse than that of intestinal-type GC.
According to follow-up statistics, the difference in survival rate 5 years after surgery for intestinal GC and diffuse GC was statistically significant (P < 0.05), and the survival rate of diffuse GC was lower than that of intestinal GC after 5 years (see Fig. 2). The 5-year survival rate of patients receiving surgery was significantly higher than that of patients without surgery P < 0.05) (see Fig. 5A). In patients with diffuse GC, there was a statistically significant difference between the 5-year survival rate of those receiving radiotherapy and the 5-year survival rate of patients who did not receive radiotherapy (P > 0.05), and the 5-year survival rate of patients receiving radiotherapy was higher than that of patients who did not receive radiotherapy (see Fig. 5B).
We found that there was a recent article that was also based on the SEER database and Lauren classification of GC, but its conclusions were very inconsistent . This article suggests that diffuse-type has a better prognosis than intestinal-type GC. The results also showed that diffuse types occur in younger female patients and tend to occur in upper gastric areas, with smaller sizes and more lymph nodes involved than those in intestinal types. Table 1 detailed the clinical characteristics of both types, however, the differences between them may be due to several reasons. Firstly, early GC was included in this study, it meant all stages of GC were contained. Secondly, in addition to the intestinal and diffuse coding, the coding of the WHO classification was also included in this research.
At the same time, we should admit that the study has some shortcomings. First, some important clinical information is missing from the SEER database, such as chemotherapy used, omics data for bioinformatics analysis, and the data of modern prognostic factors such HER-2 status were not complete in SEER. Hence, a few potential prognostic factors cannot be applied into our study. In addition, a majority of cases were not updated to the newest AJCC staging system in the database. Our results suggested that diffuse-type carried a worse prognosis but a lower risk of LNM than intestinal-type. It is remarkable that clinicians should take their lymphatic metastasis seriously.