Annals of Coloproctology

Original Articles

Colorectal cancer

Are the width, length, depth, and area of submucosal invasion predictive of lymph node metastasis in pT1 colorectal cancer?: Olga Maynovskaia, Evgeny Rybakov, Stanislav Chernyshov, Evgeniy Khomyakov, Sergey Achkasov; Ann Coloproctol. 2023;39(6):484-492. Published online December 26, 2023; DOI: https://doi.org/10.3393/ac.2023.00087.0012

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Purpose
Submucosa-limited (pathological T1, pT1) colorectal cancers (CRCs) pose a continuing challenge in the choice of treatment options, which range from local excision to radical surgery. The aim of this study was to evaluate the morphometric and morphologic risk factors associated with regional lymph node metastasis (LNM) in pT1 CRC.
Methods
We performed a histological review of patients who underwent oncological resection between 2016 and 2022. Tumor grade, budding, poorly differentiated clusters (PDCs), cancer gland rupture, lymphovascular invasion (LVI), and presence of deep submucosal invasion (DSI), as well as width, length, total area, and area of DSI, were evaluated as potential risk factors for LNM.
Results
A total of 264 cases of colon and rectal carcinomas with invasion into the submucosal layer (pT1) were identified. LNM was found in 46 of the 264 cases (17.4%). All morphometric parameters, as well as DSI (P=0.330), showed no significant association with LNM. High grade adenocarcinoma (P=0.050), budding (P=0.056), and PDCs (P<0.001) were associated with LNM. In the multivariate analysis, LVI presence remained the only significant independent risk factor (odds ratio, 15.7; 95% confidence interval, 8.5–94.9; P<0.001).
Conclusion
The DSI of T1 CRC, as well as other morphometric parameters of submucosal tumor spread, held no predictive value in terms of LNM. LVI was the only independent risk factor of LNM.

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IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer
Giulia Becherucci, Cesare Ruffolo, Melania Scarpa, Federico Scognamiglio, Astghik Stepanyan, Isacco Maretto, Andromachi Kotsafti, Ottavia De Simoni, Pierluigi Pilati, Boris Franzato, Antonio Scapinello, Francesca Bergamo, Marco Massani, Tommaso Stecca, An
Surgery.2025; 178: 108902. CrossRef
Long-term outcomes and lymph node metastasis following endoscopic resection with additional surgery or primary surgery for T1 colorectal cancer
Pin-Chun Chen, Yi-Kai Kao, Po-Wen Yang, Chia-Hung Chen, Chih-I Chen
Scientific Reports.2025;[Epub] CrossRef

Gland Attenuation, a Novel Morphological Feature of Colorectal Cancer: Evidence for an Epithelial-Mesenchymal Transition: Tae-Hwa Baek, Dong-Wook Kang, Joo-Heon Kim, Hyun-Jin Son; Ann Coloproctol. 2018;34(4):187-196. Published online August 31, 2018; DOI: https://doi.org/10.3393/ac.2017.12.02

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Abstract PDF

Purpose
Along the invasive margin, colorectal cancer may show distinctive morphologic changes characterized by an asymmetrically attenuating tumor gland with loss of polarity. The author coined the term ‘gland attenuation (GA)’ for these peculiar changes. The aims of this study were to compare the immunoreactivity of the epithelial-mesenchymal transition (EMT) markers E-cadherin and β-catenin and thus determine whether EMTs occurs at tumor budding (TB) or GA sites and to assess the association of TB and/or GA levels with clinicopathological parameters and prognosis.
Methods
Expression patterns of E-cadherin and β-catenin in the tumor centers at GA and TB sites were examined in 101 patients with well or moderately differentiated CRCs, and the prognostic significance of TB and/or GA was statistically evaluated.
Results
GA foci, as well as TB foci, revealed loss of membranous and cytoplasmic E-cadherin expressions and aberrant β-catenin expression with reduced membranous expression and increased localization to the nucleus, suggesting that EMTs occur in GA as well as in TB. The high-TB and the TB-dominant groups were significantly correlated with advanced invasion depth, presence of lymph node metastasis, advanced pathologic staging and presence of lymphovascular invasion. The high-TB and the TB-dominant groups showed poor overall survival (OS) and recurrence-free survival (RFS), and high TB was an independent prognostic factor in the multivariate analyses for OS and RFS.
Conclusion
This study showed evidence that EMTs occurs at GA sites as well as TB foci. TB is a strong and independent prognostic factor, and TB-dominance may be an indicator of adverse clinical outcome.

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Tumor budding as a potential prognostic marker in determining the behavior of primary liver cancers
Betul Unal, Mennan Yigitcan Celik, Elif Ocak Gedik, Cumhur Ibrahim Bassorgun, Gulsum Ozlem Elpek
World Journal of Hepatology.2023; 15(6): 775. CrossRef
Identification of a Novel Epithelial–Mesenchymal Transition Gene Signature Predicting Survival in Patients With HNSCC
Wei Xin, Chaoran Zhao, Longyang Jiang, Dongmei Pei, Lin Zhao, Chengpu Zhang
Pathology and Oncology Research.2021;[Epub] CrossRef
Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial–mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma
Shinya Neri, Toshi Menju, Terumasa Sowa, Yojiro Yutaka, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi F. Chen-Yoshikawa, Toshihiko Sato, Makoto Sonobe, Akihiko Yoshizawa, Hironori Haga, Hiroshi Date
Lung Cancer.2019; 128: 13. CrossRef
MicroRNA‐198‐5p inhibits the migration and invasion of non‐small lung cancer cells by targeting fucosyltransferase 8
Siyao Wang, Xin Zhang, Chunlu Yang, Shun Xu
Clinical and Experimental Pharmacology and Physiology.2019; 46(10): 955. CrossRef

The Prognostic Significance of Tumor Budding, Tumor Nodules, and Lymph Node Extracapsular Extension in Stage III Colorectal Cancer Patients.: Kim, Seong Ah , Shin, Ok Ran , Kim, Hyong Ran , Cho, Hang Ju , Seo, Hak Jun , Kim, Kee Hwan , Kim, Ji Il , An, Chang Hyeok , Oh, Seung Tack , Kim, Jeong Soo; J Korean Soc Coloproctol. 2007;23(6):460-476.; DOI: https://doi.org/10.3393/jksc.2007.23.6.460

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PURPOSE
The prognosis of advanced colorectal cancer patients may be different even for the same TNM staging. The characteristic features of tumors, such as tumor budding, tumor nodules, and extracapsular extension (ECE) of lymph nodes, can influence the disease progression and the outcome for patients. Tumor budding occurs what at the invasion front of colorectal adenocarcinomas, tumor cells, singly or in small aggregates, become detached from the neoplastic glands, and it can be divided it into two groups, low grade (0~16 foci in a field) and high grade (17 or more foci in a field). A tumor nodule is histologically identified within the fatty tissue or the detached fatty tissue around the dissected lymph nodes, or is a place picked up as lymph nodes from resected specimens which contain no lymph node components. ECE is defined as a tumor extension beyond the node capsule. The aims of this study were to evaluate the clinical significance of tumor budding, tumor nodules, and ECE of lymph nodes as prognostic factors in Stage III colorectal cancer patients.
METHODS
We analyzed the disease-free and overall 5-year survival rates and recurrence rates in 94 Stage-III colorectal cancer patients according to tumor the budding intensity, the tumor nodules, and the lymph node ECE status.
RESULTS
Of the entire group, the 5-year disease-free and overall survival rates were 49%, and 50%, respectively. The 5-year disease-free and overall survival rates were higher in the low-grade tumor budding group than in the high-grade group (58% vs 33%, P=0.045, 61% vs 39%, P=0.003). The 5-year disease-free and overall survival rates in patients with tumor nodules were lower than those in patients without one (44% vs 69%, P=0.086, 47% vs 77%, P=0.018). The recurrence rate was also higher in the group with tumor nodules than without one (80% vs 52%, P=0.045). The 5-year disease-free and overall survival rates were higher in the ECE negative group than in the positive one (68% vs 37%, P=0.018, 75% vs 42%, P=0.001). The recurrence rate was also higher in the ECE positive group than in the negative group (78% vs 46%, P=0.008). The existence of ECE and tumor nodule were strongly related to systemic recurrence (P=0.006, P=0.033), but not to the local recurrence (P=0.777, P=0.611). Considering the analysis of the recurrence pattern by N stage classification, there is no statistical difference in the N2 patient group, but there was in the existence of ECE and tumor nodule were strongly related to the systemic recurrence in N1 group (P=0.019, P=0.028). These three factors were scored according to the existence, and the score range was divided into two prognostic groups, high risk group (> or =2) and low risk group (<2). The high risk group was significantly associated with systemic recurrence (P= 0.004) rather than recurrence (P=0.865), and these score value were only significant in the N1 patient group (P=0.007) rather than in the N2 group (P=0.927). The high risk group also showed poor overall survival rate compared with the low risk one in only the N1 group (P=0.002), but nof in the N2 group (P=0.193). On multivariate analysis, UICC stage and ECE were two significant factors for tumor recurrence and the 5-year disease-free survival rate.
CONCLUSIONS
These data showed that even if similar lymph node metastasis existed in advanced colorectal cancer patients, there was a different 5-year disease-free survival rate and overall survival rate according to the tumor budding, tumor nodule, and ECE status. On multivariate analysis, UICC stage and ECE were two significant factors for the tumor recurrence and the 5-year disease-free survival rate. Our results suggest that tumor budding, tumor nodule, and ECE of lymph node are excellent parameters to provide a confident prediction of clinical outcome.

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Tumor Budding and Survival After Potentially Curative Resection of Node-Positive Colon Cancer
Joanne Sy, Caroline L.-S. Fung, Owen F. Dent, Pierre H. Chapuis, Les Bokey, Charles Chan
Diseases of the Colon & Rectum.2010; 53(3): 301. CrossRef
The Relatioships Between Tumor-related Gene Expression and Tumor Budding, Tumor Nodule and Lymph Node Extracapsular Extension in Colorectal Cancer
Hyun Jong Kang, Hang Joo Cho, Gi Chang Kang, Kee Hwan Kim, Won Kyung Kang, Ji Il Kim, Jong Kyung Park, Seungtack Oh, Jeong Soo Kim, Chang Hyeok An
Journal of the Korean Society of Coloproctology.2009; 25(1): 1. CrossRef

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