Clinical significance of coexisting histological diffuse type in stage II/III gastric cancer

Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two main types: intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type that are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1-based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathological mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy. The clinicopathological data of 968 patients with gastric carcinoma who underwent gastrectomy between 2007 and 2016 at Osaka City University Hospital were retrospectively analyzed. In the present study, tumors containing Sig or Por2 were classified as diffuse type, and those not containing them were classified as intestinal type. There were 307 cases of diffuse type and 661 cases of intestinal type. Diffuse type included 189 cases with Sig. A pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III gastric cancer. Patients with diffuse type had a worse overall survival rate than those with intestinal type at stage III gastric cancer. Among the patients who received S-1 adjuvant chemotherapy, the prognosis of patients with stage III gastric cancer with Sig but not Por2 was significantly worse compared with that of patients with intestinal type. Therefore, the present study revealed that the coexistence of Sig in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. The current findings suggested that, since mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy was performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in patients with stage III gastric cancer.