Prognostic significance of tumor budding in biliary tract cancer

Regmi, Parbatraj; Paudyal, Aliza; Paudyal, Pranita; Hu, Hai‐Jie; Liu, Fei; Ma, Wen‐Jie; Jin, Yu; Li, Fuyu

doi:10.1016/j.ejso.2021.08.008

Cited by 9 publications

(10 citation statements)

References 35 publications

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“…All studies investigating TB in patients with CC published thus far graded the TB based on ITBCC scoring system [ 11 – 15 , 17 – 19 , 23 ]. Most of these studies classified TB into low and intermediate/high groups based on the cut-off value of 5 [ 11 , 12 , 14 , 15 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…By introducing this concept, studies on the prognostic significance of TB in various cancer types, such as pancreatic, gallbladder, esophageal, and gastric cancers, have been conducted [7][8][9][10]. Although relevant studies have recently been performed to evaluate the importance of TB in CC, the number remains limited, and only 10 papers have been published to date (as of March 2023) [11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma

Kim

Ahn

Kwon

et al. 2023

Pathol. Oncol. Res.

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Background: Tumor budding is considered a prognostic factor in several solid cancer types. However, we lack comprehensive information on the importance of tumor budding in cholangiocarcinoma. Therefore, we aimed to assess the prognostic value of tumor budding in intrahepatic and extrahepatic cholangiocarcinomas and to evaluate its correlations with other clinicopathological parameters.Methods: We monitored 219 patients who underwent surgery for intrahepatic or extrahepatic cholangiocarcinoma at the Pusan National University Hospital between 2012 and 2021. Tumor budding was evaluated using the International Tumor Budding Consensus Conference scoring system. Tumor budding was classified into low (0–4), intermediate (5–9), and high (≥10). For statistical analysis, tumor budding was divided into two groups based on the cut-off value of 10 (lower: 0–9 vs. higher: ≥10). The correlations between clinicopathological parameters were examined using the chi-square and Fisher’s exact test. The prognostic values of the variables were analyzed using the log-rank test and Cox regression analysis.Results: Low, intermediate, and high tumor buddings were identified in 135 (61.6%), 63 (28.8), and 21 (9.6%), patients, respectively. Higher tumor budding was related to the presence of lymphatic invasion (p = 0.017), higher tumor grade (p = 0.001), higher N category (p = 0.034). In the univariable and multivariable analyses, higher tumor budding was associated with shorter disease-free survival in 97 (44.3%) patients who underwent R0 resection (p < 0.001 and p = 0.011). Tumor budding did not significantly correlate with disease-specific survival in entire patients.Conclusion: Tumor budding may serve as a prognostic factor for intrahepatic and extrahepatic cholangiocarcinomas treated with R0 resection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma

Kim

Ahn

Kwon

et al. 2023

Pathol. Oncol. Res.

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“…TB is associated with epithelial-mesenchymal transition [9,23] and is a well-known prognostic factor for colorectal cancer [9,[24][25][26]. In various solid cancers, including biliary tract, breast, head and neck, lung, pancreas, and urinary tract cancers, TB has been recognized as a poor prognostic factor due to its close association with LNM [9,[27][28][29][30][31][32][33][34][35]. TB has also emerged as a potential predictor of LNM in GC lesions [3,[9][10][11][12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Two Cases of Lymph Node Metastasis Found in Differentiated, Small-Sized Gastric Adenocarcinomas: Did Tumor Budding Play a Critical Role?

Lee,

Chong,

Seo

et al. 2023

Medicina

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Background: Endoscopic resection (ER) is a minimally invasive therapeutic approach for early gastric cancer (EGC), particularly for cases with a low risk of lymph node metastasis (LNM). Tumor budding (TB) has gained attention as a potential prognostic indicator for LNM in EGC. Case Presentation: We report two cases—a 73-year-old and an 81-year-old male patient—who presented with gastric adenocarcinoma. Both patients had small-sized, differentiated, and intramucosal adenocarcinomas. However, high-grade TBs per high-power field under ×200 magnification at the invasive front and LNMs were found in both cases. Conclusions: These cases conformed to the post-ER observation guidelines of the current treatment protocol, yet demonstrated LNMs. We found that TB could serve as an effective prognostic marker for LNM compared to traditional risk factors. The aim of this study is to re-examine the ability of TB to predict LNM in EGC, thereby providing an impetus for reconsideration and potential revision of the current treatment guidelines for EGC.

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“…Both CSCs and tumor buds are present at the tumor’s invasive front ( Kodama et al, 2017 ; Lugli et al, 2017 ). High-grade tumor budding is an independent prognostic factor for various solid tumors ( Almangush et al, 2016 ; Cappellesso et al, 2017 ; Lawlor et al, 2019 ; Park et al, 2020 ; Regmi et al, 2022 ) and correlates with lymph node metastasis ( Nakagawa et al, 2013 ; Takamatsu et al, 2019 ) and the depth of tumor invasion ( Yamakawa et al, 2019 ; Xie et al, 2019 ). Nevertheless, we found that the presence or absence of tumor budding did not correlate with any clinicopathological variables ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor budding of cervical squamous cell carcinoma: epithelial-mesenchymal transition-like cancer stem cells?

Zheng

Xie

et al. 2022

PeerJ

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Recent evidence indicates that cancer stem cells (CSCs) are the origin of cancers. Scientists have identified CSCs in various tumors and have suggested the existence of a variety of states of CSCs. The existence of epithelial–mesenchymal transition (EMT)-like CSCs has been confirmed in vitro, but they have not been identified in vivo. Tumor budding was defined as single cell or clusters of ≤ 5 cells at the invasive front of cancers. Such tumor budding is hypothesized to be closely related to EMT and linked to CSCs, especially to those migrating at the invasive front. Therefore, tumor budding has been proposed to represent EMT-like stem cells. However, this hypothesis has not yet been proven. Thus, we studied the expression of EMT markers, certain CSC markers of tumor budding, and the tumor center of cervical squamous cell carcinoma (CxSCC). We performed tissue chip analyses of 95 primary CxSCCs from patients. Expression of EMT and CSC markers (E-cadherin, β-catenin, vimentin, Ki67, CD44, SOX2 , and ALDH1A1) in a set of tumor samples on tissue chips (87 cases of tumor budding/the main tumor body) were evaluated by immunohistochemistry. We found that the cell-membranous expression of β-catenin was stronger in the main tumor body than in tumor buds. Compared with the main tumor body, tumor buds had reduced proliferative activity as measured by Ki67. Moreover, vimentin expression was high and E-cadherin expression was low in tumor buds. Expression of EMT-related markers suggested that tumor buds were correlated with EMT. We noted that CxSCC tumor buds had a CD44negative/low/SOX2high/ALDH1A1high staining pattern, indicating that tumor buds of CxSCC present CSC-like immunophenotypic features. Taken together, our data indicate that tumor buds in CxSCC may represent EMT-like CSCs in vivo.

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Prognostic significance of tumor budding in biliary tract cancer

Cited by 9 publications

References 35 publications

Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma

Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma

Two Cases of Lymph Node Metastasis Found in Differentiated, Small-Sized Gastric Adenocarcinomas: Did Tumor Budding Play a Critical Role?

Tumor budding of cervical squamous cell carcinoma: epithelial-mesenchymal transition-like cancer stem cells?

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