High rate of lymphogenic metastases and poor prognosis in patients with mixed gastric carcinoma

Background. Current information of the prognosis of mixed-type gastric cancer (GC) is poor. A few studies have shown that mixed GC differs from other types in the Lauren classification by more frequent of the lymph nodes metastasis and an aggressive behavior.

Aim. To study the prognosis of mixed GC versus other Lauren GC types and evaluate the prognostic value of the predominant component in mixed carcinoma.

Materials and methods. 315 patients with GC were reviewed by using a semi-quantitative assessment of the proportion of the diffuse and intestinal components of the tumor after surgical treatment by evaluation of the specimens slides to clarify the type of GC according to the Lauren classification, as well as the proportion of each component in the mixed GC. 166 patients (52.7%) with GC had the intestinal type, 72 (22.8%) had the diffuse type, 60 (19.0%) had the mixed type, and 17 (5.4%) had an unclassified type.

Results. Mixed-type GC exhibited more aggressive behavior than intestinal and diffuse types of GC. It was characterized by deeper invasion of the gastric wall and more extensive lymphogenic metastasis. Early cancer (pT1b) was diagnosed in only 1 (1.7%) case, while in intestinal and diffuse types, it was detected in 18.6% and 29.2% of patients (p<0.01), respectively. Invasion into the serous membrane of the stomach was reported in 56.7% of cases versus 45.1% (p=0.1270) and 27.7% (p=0.0008), respectively. Mixed GC metastasized to regional lymph nodes metastasis more frequently than intestinal or diffuse cancer (80% vs. 59.0% and 29.2%, respectively; p<0.004). The average number of lymphogenic metastases was significantly higher than in intestinal and diffuse GC types (6.73±7.51 vs 3.58±5.04 and 2.15±4.39, respectively; p<0.001). More frequently lymph node involvement in patients with mixed GC was observed with a similar depth of tumor invasion in the compared groups. In the study population, the 5-year overall survival (OS) in patients with mixed-type GC was significantly lower than in patients with intestinal and diffuse-type GC: 26.4% vs. 58.7% (p=0.00000) and 51.1% (p<0.03). Stage-by-stage analysis showed significant differences in OS between mixed and intestinal GC in the largest group of patients with stage III disease and found no significant differences between mixed and diffuse GC at any stage. If the diffuse component was prevailed in patients with mixed-type GC, the 5-year OS rate was 37.9%; if the intestinal component prevailed, there were no survivors 5 years after surgery, and the 3-year OS rate was 12.8% (Log rank test; p=0.022). The frequency of metastatic lesions of regional lymph nodes in subgroup 1 was lower than in subgroup 2 (74.4% vs. 94.1%; p=0.0856).

Conclusion. Mixed GC is diagnosed in later stages compared to other types of GC according to the Lauren classification, which translates into lower OS rates. This histological type shows a higher rate of lymphatic metastases, even with the same depth of tumor invasion. In a step-by-step analysis, OS in patients with mixed GC was significantly worse than that in the intestinal type, and was comparable to the results of treatment of diffuse GC. The predominant component assessment in mixed carcinoma may prove to be an additional prognostic factor.