High proportion of stroma is an independent prognostic factor in both intestinal and diffuse histological subtypes of gastric adenocarcinoma.

Tumor budding has been associated with poor prognosis in several cancer types, but its significance in gastric cancer is unknown. The aim of this study was to assess the prognostic significance of tumor budding in gastric adenocarcinoma, and its main histological types. Some 583 gastric adenocarcinoma patients who underwent surgery in Oulu University Hospital during the years 1983-2016 were included in this retrospective cohort study. Tumor budding was counted per 0,785mm 2 fields from the slides originally used for diagnostic purposes. Patients were divided into low-(<10 buds) and high budding (≥10 buds) groups. Tumor budding was analyzed in relation to 5year survival and overall survival. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Determining tumor budding was difficult in diffuse type cancer due to the uncohesive growth pattern of these tumors. Patients with high tumor budding had worse 5-year survival compared to patients with low tumor budding (adjusted HR 1.55, 95% CI 1.20 -2.01). In intestinal type adenocarcinomas, the high budding group had significantly poorer 5-year survival compared to the low budding group (adjusted HR 1.57, 95% CI 1.14-2.15). There were no differences in 5-year survival between the budding groups in the diffuse type adenocarcinoma. In conclusion, high tumor budding is an independent prognostic factor in gastric adenocarcinoma, but its value is limited to intestinal type of gastric adenocarcinoma. In diffuse type gastric adenocarcinoma, the assessment of tumor budding is hardly feasible and it does not have prognostic relevance.

Tumour-stroma ratio (TSR) is a novel potential prognostic factor in cancers and based on the proportions of stroma and tumour area. The prognostic value of TSR in gastric cancer is incompletely known. The aim of this study was to estimate prognostic significance of TSR in gastric adenocarcinoma. A search of PubMed (MEDLINE), Web of Science, EMBASE, Cochrane and Scopus databases was performed. A meta-analysis was conducted on five-year survival in gastric cancer patients using inverse variance random-effects methods. The literature search yielded 5329 potential titles, of which a total of seven studies were eligible. Results of six studies including a total of 1779 patients were pooled in the meta-analysis. Only 23 (1.3%) of the patients received neoadjuvant therapy. All six studies had a cut-off of 50% for the proportion of stroma when dividing the patients into low- and high stroma groups. Low TSR (high amount of stroma) was strongly associated with increased five-year mortality (hazard ratio 2.19, 95% CI 1.69–2.85). In conclusion, TSR is a strong prognostic factor in gastric cancer. It could be used to estimate prognosis of gastric cancer patients not receiving neoadjuvant chemotherapy. Further studies including patients receiving neoadjuvant therapy are recommended.