Assessment of Tumor Budding in Colorectal Carcinoma by Cytokeratin Staining
DOI:
https://doi.org/10.52206/jsmc.2024.14.4.882Abstract
Background: Tumor budding has been receiving increasing recognition in many studies, as an important independent prognostic factor in colorectal carcinoma (CRC). In histopathological reporting of CRC, it is defined as the presence of single tumor cell or small clusters of up to 4 cells in the advancing edge of the tumor stroma.
Objectives: We aim to determine the frequency of tumor budding by cytokeratin staining, in relation to the depth of invasion, lymph node involvement, perineural invasion and tumor grade in colorectal carcinoma.
MaterialS and Methods: This descriptive cross sectional study was carried out from November 2022 till April 2023. During these six months, 62 hemi-colectomy specimens of colorectal carcinoma, received in histopathology lab were included in this study. The samples belonged to the patients who were biopsy proven cases of colorectal carcinoma and those who were not given any pre-operative therapy. The age range was from 20 to 80 years including both genders. After processing the tumor sections were examined under microscope, on both conventional stains and the Pan-Cytokeratin (AE1/AE3) stain. The results were interpreted by consultant histopathologists for tumor budding score. Tumor buds less than 10 per high power field was considered as low score. 10 and more buds per high power field were considered as high score.
Results: When tumor grade and depth of invasion was compared to tumor budding score, the comparison was not statistically significant with p value of 0.06 and 0.937 respectively, whereas its relationship with lymph node involvement and perineural invasion was found to be statistically highly significant with p value of < 0.001.
Conclusion: This study concluded that tumor budding has a statistically significant relationship with lymph node metastasis and perineural invasion, but not with tumor grade and depth of invasion (T stage).
Keywords: Colorectal carcinoma, Drade, Lymph node, Pan-cytokeratin, Perineural invasion, Stage.
References
Sung H, Ferlay J, Siegel RL. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021 May;71(3):209-49. DOI: https://doi.org/10.3322/caac.21660
Mori G, Pasca MR. Gut microbial signatures in sporadic and hereditary colorectal cancer. International Journal of Molecular Sciences. 2021 Jan 28;22(3):1312. DOI: https://doi.org/10.3390/ijms22031312
Lewandowska A, Rudzki G, Lewandowski T. Risk factors for the diagnosis of colorectal cancer. Cancer Control. 2022 Jan 4;29: 10732748211056692. DOI: https://doi.org/10.1177/10732748211056692
Tehrani KF, Park J, Chaney EJ, Tu H, Boppart SA. Nonlinear imaging histopathology: a pipeline to correlate gold-standard hematoxylin and eosin staining with modern nonlinear microscopy. IEEE Journal of Selected Topics in Quantum Electronics. 2023 Jan 2;29(4: Biophotonics):1-8. DOI: https://doi.org/10.1109/JSTQE.2022.3233523
Cyr DP, Pun C, Shivji S, Mitrovic B, Duan K, Tomin R, et al. Tumor Budding Assessment in Colorectal Carcinoma: Normalization Revisited. The American Journal of Surgical Pathology. 2024 Mar 1;48(3):251-65. DOI: https://doi.org/10.1097/PAS.0000000000002166
Pyo JS, Choi JE, Kim NY, Min KW, Kang DW. Comparison between Peritumoral and Intratumoral Budding in Colorectal Cancer. Biomedicines. 2024 Jan 17;12(1):212. DOI: https://doi.org/10.3390/biomedicines12010212
Basu B, Karmakar S, Basu M, Ghosh MK. USP7 imparts partial EMT state in colorectal cancer by stabilizing the RNA helicase DDX3X and augmenting Wnt/â-catenin signaling. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2023 Apr 1;1870(4):119446. DOI: https://doi.org/10.1016/j.bbamcr.2023.119446
Qu Q, Wu D, Li Z, Yin H. Tumor budding and the prognosis of patients with metastatic colorectal cancer: A meta-analysis. International journal of colorectal disease. 2023 May 24;38(1):141. DOI: https://doi.org/10.1007/s00384-023-04423-8
Mishra PP, Madan K, Biswas S, Rao AC, Shetty R, Panda P. Tumour budding in colorectal carcinoma: Association with other histopathological prognostic parameters. IP Archives of Cytology and Histopathology Research 2022;7(1):26-31. DOI: https://doi.org/10.18231/j.achr.2022.006
Li J, Ma Y, Wen L, Zhang G, Huang C, Wang J. Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis. Systematic Reviews. 2024 Jan 9;13(1):22. DOI: https://doi.org/10.1186/s13643-023-02441-9
Kristensen MP, Korsgaard U, Timm S, Hansen TF, Zlobec I, Hager H, et al. The prognostic value of tumor budding in a thoroughly characterized stage II colon cancer population in the context of a national screening program. Human Pathology. 2024 Feb 28. DOI: https://doi.org/10.1016/j.humpath.2024.02.010
Bokhorst JM, Blank A, Lugli A, Zlobec I, Dawson H, Vieth M, et al. Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning. Modern pathology. 2020 May 1;33(5):825-33. DOI: https://doi.org/10.1038/s41379-019-0450-2
Fauzi MF, Chen W, Knight D, Hampel H, Frankel WL, Gurcan MN. Tumor budding detection system in whole slide pathology images. Journal of medical systems. 2020 Feb;44:1-0. DOI: https://doi.org/10.1007/s10916-019-1515-y
Koelzer VH, Assarzadegan N, Dawson H, Mitrovic B, Grin A, Messenger DE. Cytokeratin-based assessment of tumour budding in colorectal cancer: analysis in stage II patients and prospective diagnostic experience. J Pathol Clin Res. 2017; 3(3):171-8. DOI: https://doi.org/10.1002/cjp2.73
Deb B, Jacob SE. Predictive power of tumour budding for lymph node metastasis in colorectal carcinomas: A retrospective study. Indian J Med Res. 2019; 150(6): 6359. DOI: https://doi.org/10.4103/ijmr.IJMR_1268_17
Graham RP, Vierkant RA, Tillmans LS, Wang AH, Laird PW, Weisenberger DJ, et al. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population- based Cohort. Am J Surg Pathol. 2015; 39(10): 1340-6. DOI: https://doi.org/10.1097/PAS.0000000000000504
Zlobec I, Bihl MP, Foerster A, Rufle A, Lugli A. The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer. Histopathology. 2012; 61(5): 777-87. DOI: https://doi.org/10.1111/j.1365-2559.2012.04273
Huh JW, Kim HC, Kim SH, Park YA, Cho YB, Yun SH, et al. Mismatch repair system and p53 expression in patients with T1 and T2 colorectal cancer: predictive role of lymph node metastasis and survival. J Surg Oncol. 2014; 109(8): 848-52. DOI: https://doi.org/10.1002/jso.23592
Okuyama T, Oya M, Ishikawa H. Budding as a Useful Prognostic Marker in pT3 Well- or Moderately-Differentiated Rectal Adenocarcinoma. J Surg Oncol. 2003; 83(1): 42-7. DOI: https://doi.org/10.1002/jso.10230
Nakadoi K, Tanaka S, Kanao H, Terasaki M, Takata S, Oka S, et al. Management of T1 colorectal carcinoma with special reference to criteria for curative endoscopic resection. J Gastroenterol Hepatol. 2012; 27(6): 1057-62. DOI: https://doi.org/10.1111/j.1440-1746.2011.07041.x
Sert Bektaþ S, Inan Mamak G, Cýrýþ IM, Bozkurt KK, Kapucuoðlu N. Tumor budding in colorectal carcinomas. Turk Patoloji Derg. 2012; 28(1): 61-6. DOI: https://doi.org/10.5146/tjpath.2012.01099
Mehta A, Goswami M, Sinha R, Dogra A. Histopathological significance and prognostic impact of tumor budding in colorectal cancer. Asian Pacific journal of cancer prevention: APJCP. 2018;19(9):24-47. DOI: https://doi.org/10.22034/APJCP.2018.19.9.2447
Wang LM, Kevans D, Mulcahy H, O'Sullivan J, Fennelly D, Hyland J, et al. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer. Am J Surg Pathol. 2009; 33(1): 134-41. DOI: https://doi.org/10.1097/PAS.0b013e318184cd55
Miyachi H, Kudo SE, Ichimasa K, Hisayuki T, Oikawa H, Matsudaira S, et al. Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis. J Gastroenterol Hepatol. 2016; 31(6): 1126-32. DOI: https://doi.org/10.1111/jgh.13257
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