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.

Aims Histological assessment of stromal maturity is a potential prognostic factor in colorectal cancer, but its applicability in gastric adenocarcinoma is completely unknown. The aim of this study was to evaluate the feasibility and prognostic significance of assessing stromal maturity in gastric adenocarcinoma. Methods and results This study was conducted retrospectively in a cohort of 583 gastric adenocarcinoma patients treated surgically in Oulu University Hospital, Finland between 1983 and 2016. The original diagnostic slides were used for assessment of stromal maturity. Patients were divided into mature stroma and immature stroma groups, and stromal maturity was analysed in relation to 5‐year and overall survival (OS). The primary outcome of the study was 5‐year survival, and the secondary outcome was OS. The kappa‐coefficient for interobserver agreement was 0.609. Patients with immature stroma had worse 5‐year survival compared to patients with mature stroma [adjusted hazard ratio (HR) = 1.32, 95% confidence interval (CI) = 1.06–1.64]. Stromal maturity was significantly associated with 5‐year survival in intestinal‐type subgroup (adjusted HR = 0.63, 95% CI = 1.20–2.21), but not in the diffuse‐type subgroup (adjusted HR = 1.21, 95% CI = 0.87–1.70). Conclusions Stromal maturity is an independent prognostic factor in gastric adenocarcinoma, and it can be analysed with moderate reproducibility.

Background Tumour budding and low tumour–stroma ratio (TSR) are associated with poor prognosis in some cancers, but their value in Western hepatocellular carcinoma is unclear. The prognostic value of tumour budding and TSR in hepatocellular carcinoma was examined. Methods Some 259 hepatocellular carcinoma patients treated in Oulu University Hospital 1983–2018 were included in this retrospective cohort study. Tumour budding and TSR were analysed from the haematoxylin- and eosin-stained original diagnostic slides, by dividing patients into bud-negative (0 bud) or bud-positive (≥1 bud) groups, and into high TSR (<50%) and low TSR (≥50%) groups. Surgically treated patients (n = 47) and other treatments (n = 212) were analysed separately. Primary outcomes were overall, and disease-specific 5-year mortality was adjusted for confounding factors. Results Surgically treated patients with positive tumour budding had increased 5-year overall (adjusted HR 3.87, 95% CI 1.10–13.61) and disease-specific (adjusted HR 6.17, 95% CI 1.19–31.90) mortality compared with bud-negative patients. In surgically treated patients, TSR had no effect on 5-year overall (adjusted HR 2.03, 95% CI 0.57–7.21) or disease-specific (adjusted HR 3.23, 95% CI 0.78–13.37) mortality. No difference in survival related to tumour budding and TSR in non-surgically treated patients was observed. Conclusions Tumour budding is a prognostic factor in surgically treated hepatocellular carcinoma.

Purpose: To examine and compare the prognostic value of immune cell score (ICS) and Klintrup–Mäkinen (KM) grade in gastric cancer. Methods: Gastric adenocarcinoma tissues from samples of 741 patients surgically treated in two hospitals in Finland were assessed for ICS and KM grade. Cox regression with adjustment for confounders provided hazard ratios (HRs) and 95% CIs. Subgroup analyses were performed in intestinal and diffuse type subgroups. The primary outcome was 5-year overall survival. Results: High ICS was associated to longer 5-year survival (adjusted HR 0.70, 95% CI 0.52–0.94), compared to low ICS. The difference was significant in intestinal type subgroup (adjusted HR 0.54, 95% CI 0.36–0.81) but not in diffuse type subgroup (adjusted HR 0.92, 95% CI 0.58–1.46). High KM grade was an independent prognostic factor for longer 5-year overall survival (adjusted HR 0.59, 95% CI 0.45–0.77) in both intestinal (adjusted HR 0.61, 95% CI 0.44–0.85) and diffuse subgroups (adjusted HR 0.52, 95% CI 0.31–0.86). ICS and KM grade were moderately correlated (ρ = 0.425). When both immune cell score and KM grade were included in the regression analysis, only KM grade remained prognostic. Conclusions: Both ICS and KM grade are prognostic factors in gastric adenocarcinoma, but immunohistochemistry-based ICS might not have additional prognostic value over hematoxylin–eosin-based KM grade.

Background: Monocarboxylate transporters (MCTs) appear to play an important role in tumor development and aggressiveness. The present study aimed to evaluate associations between cytoplasmic MCT1, MCT4, and mitochondrial cytochrome c oxidase (MTCO1) expression and clinicopathological variables or survival in gastric cancer. Material and methods: A total of 568 gastric adenocarcinoma patients were included in this retrospective cohort study. Protein expressions were detected by immunohistochemical staining. The patients were divided into low expression and high expression groups by median value. The Chi-squared test was used to compare categorical variables. The T-test was used to compare continuous variables. Expressions were analyzed in relation to 5-year survival and overall survival. Cox regression provided HRs and 95% CIs, adjusted for confounders. Results: High cytoplasmic MCT1 expression was associated statistically significantly with higher T-class (p = 0.020). High cytoplasmic MCT4 expression was associated statistically significantly with positive lymph node status (p = 0.005) and was more common in Lauren’s intestinal type (p < 0.001). Low cytoplasmic MTCO1 expression was associated statistically significantly with positive distant metastases (p = 0.030), and high cytoplasmic MTCO1 expression was associated more often with intestinal type (p = 0.044). However, MCT1, MCT4, and MTCO1 were not associated with survival. Conclusions: Monocarboxylate receptors seem to be associated with gastric cancer progression but have no independent prognostic relevance.

Tertiary lymphoid structures (TLSs) are part of immune response against cancer. Their high density and high diameter have been shown to be associated with prognosis in different cancer types. The aim of this study was to examine the prognostic significance of TLS density and diameter in gastric cancer and reproducibility of their assessments. TLS densities and maximal TLS diameter were assessed from hematoxylin–eosin (HE) stained slides of 721 surgically treated gastric cancer patients from two hospitals in Finland. Mortality hazard ratios (HRs) for TLS densities and maximal TLS diameter were analyzed. TLS densities and maximal TLS diameter were assessed with moderate interobserver agreement (Cohen's kappa 0.50–0.62). Maximal TLS density was not associated with survival (adjusted HR 0.85, 95% CI 0.70–1.02) and neither was hotspot TLS density (adjusted HR 0.85, 95% CI 0.70–1.02). High maximal TLS diameter was associated with longer survival in overall study population (adjusted HR 0.74, 95% CI 0.61–0.89) and in diffuse type subgroup (adjusted HR 0.65, 95% CI 0.50–0.85). In conclusion, high maximal TLS diameter is associated with improved survival in gastric cancer and can be assessed from HE‐stained slides. Its prognostic value might be limited to diffuse histological type.