Polish Journal of Pathology
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ISSN: 1233-9687
Polish Journal of Pathology
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Original paper

Prognostic impact of tumour budding, stromal phenotype, and CD163-positive macrophages in intestinal-type gastric adenocarcinoma

Elİf Aydin
1
,
Ömer Atmış
1
,
Hanİfe Seda Mavİlİ
1
,
Mustafa Şahbazlar
2
,
Semİn Ayhan
1

  1. Department of Pathology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
  2. Department of Medical Oncology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey
Pol J Pathol 2026; 77 (1)
Online publish date: 2026/05/14
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1. Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020; 76: 182-188.
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229-263.
3. Sexton RE, Al Hallak MN, Diab M, Azmi AS. Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer Metastasis Rev 2020; 39: 1179-1203.
4. Brierley JD, Giuliani M, O’Sullivan B, Rous B, Van Eycken L. TNM classification of malignant tumours. 9th ed. NJ: Wiley- Blackwell, Hoboken 2025.
5. Berlth F, Bollschweiler E, Drebber U, Hoelscher AH, Moenig S. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol 2014; 20: 5679.
6. Sternberg SS, Mills SE, Carter D. Sternberg’s diagnostic surgical pathology. 4th ed. Lippincott Williams & Wilkins, Philadelphia 2004.
7. Nakamura K, Kamei T, Ohtomo N, Kinukawa N, Tanaka M. Gastric carcinoma confined to the muscularis propria: how can we detect, evaluate, and cure intermediate-stage carcinoma of the stomach? Am J Gastroenterol 1999; 94: 2251-2255.
8. Hyung WJ, Lee JH, Choi SH, Min JS, Noh SH. Prognostic impact of lymphatic and/or blood vessel invasion in patients with node-negative advanced gastric cancer. Ann Surg Oncol 2002; 9: 562-567.
9. Rosai J. Rosai and Ackerman’s surgical pathology. 10th ed. Mosby, Edinburgh 2011.
10. Grigore AD, Jolly MK, Jia D, Farach-Carson MC, Levine H. Tumor budding: the name is EMT. Partial EMT. J Clin Med 2016; 5: 51.
11. Li H, Xu F, Li S, Zhong A, Meng X, Lai M. The tumor microenvironment: an irreplaceable element of tumor budding and epithelial-mesenchymal transition-mediated cancer metastasis. Cell Adh Migr 2016; 10: 1-13.
12. Lugli A, Zlobec I, Berger MD, Kirsch R, Nagtegaal ID. Tumour budding in solid cancers. Nature Rev Clin Oncol 2021; 18: 101-115.
13. Liang F, Cao W, Wang Y, Li L, Zhang G, Wang Z. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract 2013; 209: 269-275.
14. Koyuncuoglu M, Okyay E, Saatli B, Olgan S, Akin M, Saygili U. Tumor budding and E-Cadherin expression in endometrial carcinoma: are they prognostic factors in endometrial cancer? Gynecol Oncol 2012; 125: 208-213.
15. O’Connor K, Li-Chang HH, Kalloger SE, Peixoto RD, Webber DL, Owen DA, et al. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma. Am J Surg Pathol 2015; 39: 472-478.
16. Olsen S, Jin L, Fields RC, Yan Y, Nalbantoglu I. Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence. Hum Pathol 2017; 68: 26-33.
17. Kemi N, Eskuri M, Ikäläinen J, Karttunen TJ, Kauppila JH. Tumor budding and prognosis in gastric adenocarcinoma. Am J Surg Pathol 2019; 43: 229-234.
18. Gulluoglu M, Yegen G, Ozluk Y, Keskin M, Dogan S, Gundogdu G, et al. Tumor budding is independently predictive for lymph node involvement in early gastric cancer. Int J Surg Pathol 2015; 23: 349-358.
19. Anderson NM, Simon MC. The tumor microenvironment. Curr Biol 2020; 30: R921-R5.
20. Kalluri R. The biology and function of fibroblasts in cancer. Nature Rev Cancer 2016; 16: 582-598.
21. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in onco- logy. Nature Rev Clin Oncol 2017; 14: 399-416.
22. Kim KJ, Wen XY, Yang HK, Kim WH, Kang GH. Prognostic implication of M2 macrophages are determined by the proportional balance of tumor associated macrophages and tumor infiltrating lymphocytes in microsatellite-unstable gastric carcinoma. PloS One 2015; 10: e0144192.
23. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nature Immunol 2010; 11: 889-896.
24. Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Martínez-Ciarpaglini C, Cabeza-Segura M, et al. The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev 2020; 86: 102015.
25. Yin S, Huang J, Li Z, Zhang J, Luo J, Lu C, et al. The prognostic and clinicopathological significance of tumor-associated macrophages in patients with gastric cancer: a meta-analysis. PloS One 2017; 12: e0170042.
26. Alnuaimi AR, Bottner J, Nair VA, Ali N, Alnakhli R, Dreyer E, et al. Immunohistochemical expression analysis of caldesmon isoforms in colorectal carcinoma reveals interesting correlations with tumor characteristics. Int J Mol Sci 2023; 24: 2275.
27. Lee M-S, Lee J, Kim JH, Kim WT, Kim WJ, Ahn H, et al. Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer. Oncotarget 2015; 6: 40370.
28. Liu Y, Xie S, Zhu K, Guan X, Guo L, Lu R. CALD1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancers. Heliyon 2021; 7: e07257.
29. Zhao Z, Zhang Y, Guo E, Zhang Y, Wang Y. Periostin secreted from podoplanin-positive cancer-associated fibroblasts promotes metastasis of gastric cancer by regulating cancer stem cells via AKT and YAP signaling pathway. Mol Carcinogen 2023; 62: 685-699.
30. Fan C, Wang Q, Kanei S, Kawabata K, Nishikubo H, Aoyama R, et al. Periostin from tumor stromal cells might be associated with malignant progression of colorectal cancer via Smad2/3. Cancers 2025; 17: 551.
31. Liu Y, Huang Z, Cui D, Ouyang G. The multiaspect functions of periostin in tumor progression. Adv Exp Med Biol 2019; 1132: 125-136.
32. Sung PL, Jan YH, Lin SC, Huang CC, Lin H, Wen KC, et al. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma. Oncotarget 2015; 7: 4036.
33. Xue C, Du Y, Li Y, Xu H, Zhu Z. Tumor budding as a predictor for prognosis and therapeutic response in gastric cancer: a mini review. Front Oncol 2023; 12: 1003959.
34. Biliæ Z, Zovak M, Glavčiæ G, Mužina D, Ibukiæ A, Košec A, et al. The relationship between tumor budding and tumor deposits in patients with stage III colorectal carcinoma. J Clin Med 2024; 13: 2583.
35. Zlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 2010; 1: 651.
36. Guo YX, Zhang ZZ, Zhao G, Zhao EH. Prognostic and pathological impact of tumor budding in gastric cancer: a systematic review and meta-analysis. World J Gastrointestin Oncol 2019; 11: 898.
37. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012; 21: 309-322.
38. Kemi N, Eskuri M, Herva A, Leppänen J, Huhta H, Helmi- nen O, et al. Tumour-stroma ratio and prognosis in gastric adeno- carcinoma. Br J Cancer 2018; 119: 435-439.
39. Ueno H, Shinto E, Kajiwara Y, Fukazawa S, Shimazaki H, Yamamoto J, et al. Prognostic impact of histological categorisation of epithelial-mesenchymal transition in colorectal cancer. Br J Cancer 2014; 111: 2082-2090.
40. Huang X, Pan Y, Ma J, Kang Z, Xu X, Zhu Y, et al. Prognostic significance of the infiltration of CD163+ macrophages combined with CD66b+ neutrophils in gastric cancer. Cancer Med 2018; 7: 1731-1741.
41. Li J, Sun J, Zeng Z, Liu Z, Ma M, Zheng Z, et al. Tumour associated macrophages in gastric cancer: From function and mechanism to application. Clin Transl Med 2023; 13: e1386.
42. Park JY, Sung JY, Lee J, Park YK, Kim YW, Kim GY, et al. Polarized CD163+ tumor-associated macrophages are associated with increased angiogenesis and CXCL12 expression in gastric cancer. Clin Res Hepatol Gastroenterol 2016; 40: 357-365.
43. Qian S, Zhang H, Dai H, Ma B, Tian F, Jiang P, et al. Is sCD163 a clinical significant prognostic value in cancers? A systematic review and meta-analysis. Front Oncol 2020; 10: 585297.
44. Zeine R, Salwen HR, Peddinti R, Tian Y, Guerrero L, Yang Q, et al. Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors. Mod Pathol 2009; 22: 950-958.
45. Otranto M, Sarrazy V, Bonté F, Hinz B, Gabbiani G, Desmouliere A. The role of the myofibroblast in tumor stroma remodeling. Cell Adh Migr 2012; 6: 203-219.
46. Council L, Hameed O. Differential expression of immunohistochemical markers in bladder smooth muscle and myofibroblasts, and the potential utility of desmin, smoothelin, and vimentin in staging of bladder carcinoma. Mod Pathol 2009; 22: 639-650.
47. Oh HJ, Bae JM, Wen XY, Cho NY, Kim JH, Kang GH. Overexpression of POSTN in tumor stroma is a poor prognostic indicator of colorectal cancer. J Pathol Transl Med 2017; 51: 306-313.
48. Zhang T, Han Z, Chandoo A, Huang X, Sun X, Ye L, et al. Low periostin expression predicts poor survival in intestinal type gastric cancer patients. Cancer Manag Res 2018; 11: 25-36.
49. Furudate S, Fujimura T, Kakizaki A, Kambayashi Y, Asano M, Watabe A, et al. The possible interaction between periostin expressed by cancer stroma and tumor-associated macrophages in developing mycosis fungoides. Exp Dermatolo 2016; 25: 107-112.
Copyright: © 2026 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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