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Tumor Budding and Prognosis in Gastric Adenocarcinoma

Kemi, Niko, BM*; Eskuri, Maarit, BM*; Ikäläinen, Julia, BM*; Karttunen, Tuomo J., MD, PhD*; Kauppila, Joonas H., MD, PhD*,†

The American Journal of Surgical Pathology: February 2019 - Volume 43 - Issue 2 - p 229–234
doi: 10.1097/PAS.0000000000001181
Original Articles

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 histologic 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 0.785 mm2 fields from the slides originally used for diagnostic purposes. Patients were divided into low-budding (<10 buds) and high-budding (≥10 buds) groups. Tumor budding was analyzed in relation to 5-year 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 with 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 with 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 the 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.

*Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland

Department of Molecular medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Informed consent or substitute for it was obtained from all patients for being included in the study.

Conflicts of Interest and Source of Funding: supported by grants from Sigrid Jusélius Foundation (J.H.K.), Orion Research Foundation (J.H.K.), Thelma Mäkikyrö Foundation (J.H.K.), and Mary and Georg C. Ehrnroot Foundation (J.H.K.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Niko Kemi, BM, Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Aapistie 5, P.O. Box 5000, Oulu 90014, Finland (e-mail:

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