Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial

Ueno, Hideki; Ishiguro, Megumi; Nakatani, Eiji; Ishikawa, Toshiaki; Uetake, Hiroyuki; Matsuda, Chu; Nakamoto, Yoshihiko; Kotake, Masanori; Kurachi, Kiyotaka; Egawa, Tomohisa; Yasumasa, Keigo; Murata, Kohei; Ikawa, Osamu; Shinji, Seiichi; Murotani, Kenta; Matsui, Shigeyuki; Teramukai, Satoshi; Tomita, Naohiro; Sugihara, Kenichi

doi:10.1200/jco.18.02059

Cited by 95 publications

(83 citation statements)

References 31 publications

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“…Recently, tumor-stroma interaction including extramural tumor deposits without lymph node structure or tumor budding has been discussed as the mechanism of metastasis and poor prognosis [6,7]. In fact, both extramural tumor deposits and tumor budding were confirmed in our case although the relationship between intramural metastasis and these factors is unknown.…”

Section: Discussionmentioning

confidence: 54%

Intramural metastasis to the appendix from ascending colon cancer: a case report

et al. 2020

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Background: Intramural metastasis is rare in colorectal cancer, especially metastasis of ascending colon cancer to the appendix. Case presentation: A 64-year-old man was admitted to our hospital for surgery for ascending colon cancer detected by medical examination. Colonoscopy identified a type-2 tumor in the ascending colon, which was diagnosed as adenocarcinoma. Abdominal computed tomography revealed focal thickening of the ascending colon and middle of the appendix and swelling of the lymph nodes around the ileocolic artery. The patient underwent laparoscopic right hemi-colectomy with D3 lymph node dissection. Histopathological findings revealed that the ascending colon cancer was moderately differentiated adenocarcinoma with lymphatic and vascular invasion (stage IIIB; pT3N2M0). Additionally, moderately differentiated adenocarcinoma was observed mainly in the submucosa and muscularis propria of the appendix, which was approximately 10 cm proximal to the ascending colon cancer. These findings indicated intramural metastasis to the appendix from the ascending colon cancer. The patient experienced recurrence with lung metastasis 2.5 years after the first surgery. Conclusions: Intramural metastasis of ascending colon cancer to the appendix is extremely rare. Because the risk of recurrence and the prognosis for intramural metastasis has not been clarified, careful follow-up is recommended.

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Section: Discussionmentioning

confidence: 54%

Intramural metastasis to the appendix from ascending colon cancer: a case report

et al. 2020

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“…As the EMT was suggested to be associated with the tumor-budding degree (5), this parameter is routinely evaluated in the daily diagnosis of CRC and considered as a negative prognostic marker, particularly for stage II cases (6,7).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical‑based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial‑mesenchymal transition

et al. 2019

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The aim of the present study was to classify colorectal carcinoma (CRC) into molecular subtypes, based on immunohistochemical (IHC) assessments. A total of 112 CRC samples were molecularly classified based on the expression levels of epithelial-mesenchymal transition (EMT)-associated IHC markers. A total of three molecular subtypes were defined: Epithelial, membrane positivity for E-cadherin and β-catenin, negative for vimentin; mesenchymal, E-cadherin-negative, nuclear β-catenin-and vimentin-positive; and hybrid cases, epithelial tumor core and mesenchymal tumor buds. Most of the cases were diagnosed as moderately differentiated adenocarcinoma (n=89; 79.46%). The majority of cases (n=100; 89.28%) exhibited a mismatch repair proficient status (microsatellite stable CRCs). A predominance of epithelial-type (n=51; 45.54%) and hybrid CRCs (n=47; 41.96%) was observed, whereas a few cases (n=14; 12.50%) were classified as mesenchymal-type CRCs. This molecular classification was associated with pathological stage (P<0.01), pT stage (P=0.04), pN stage (P<0.01), the grade of tumor budding (P=0.04), and maspin expression in both the tumor core (P=0.04) and the invasion front (P<0.01). The mesenchymal-type cases predominantly exhibited lymph node metastases, high-grade budding and a tendency towards maspin nuclear predominance. All epithelial-type cases with maspin-only expression (n=18) were non-metastatic. Patients with CRC of the epithelial subtype and those with a lymph node ratio (LNR) ≤0.15 presented the best overall survival, followed by those with hybrid and mesenchymal subtypes. Nuclear maspin positivity was more frequent in cases with a high-budding degree compared with those with a low-budding degree (P=0.03). The EMT-associated molecular classification of CRCs may be used to identify the most aggressive CRCs, which show a mesenchymal phenotype, high-budding degree, maspin nuclear positivity and lymph node metastases. The pN stage, LNR and budding degree of patients, which can be evaluated with maspin expression, remain the most important prognostic factors.

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“…Tumour budding is a histological feature observed predominantly at the tumour front. Previous studies have revealed the clinical significance of budding, not only as a predictor of recurrence in stage II disease 5,6 , but also as a predictor of recurrence and chemosensitivity in stage III colorectal cancer [7][8][9][10][11][12] . However, in patients with stage IV disease, the significance of tumour budding remains unclear, because most analyses of stage IV colorectal cancer have had limited patient numbers 11-13 . This study aimed to investigate the prognostic impact of tumour budding in patients with stage IV CRC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and predictive values of tumour budding in stage IV colorectal cancer

Nagata¹,

Shinto²,

Yamadera³

et al. 2020

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Background: Tumour budding is an important prognostic feature in early-stage colorectal cancer, but its prognostic significance in metastatic disease has not been fully investigated. Methods: Patients with stage IV disease who had primary colorectal tumour resection without previous chemotherapy or radiotherapy from January 2000 to December 2018 were reviewed retrospectively. Budding was evaluated at the primary site and graded according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) (BD1, low; BD2, intermediate; BD3, high). Patients were categorized by metastatic (M1a, M1b) and resectional (R0/R1, R2/unresected) status. Subgroups were compared for overall (OS) and recurrence-free (RFS) survival in R0/R1 subgroups; R2/unresected patients were evaluated for the rate of tumour progression, based on change in tumour size from baseline. Results: Of 371 patients observed during the study, 362 were analysed. Patients with BD3 had a lower 5-year OS rate than those with BD1 + BD2 (18⋅4 versus 40⋅5 per cent; P < 0⋅001). Survival analyses according to metastatic and resection status also showed that BD3 was associated with shorter OS than BD1 + BD2. In multivariable analysis, BD3 (hazard ratio (HR) 1⋅51, 95 per cent c.i. 1⋅11 to 2⋅10; P = 0⋅009), T4 status (HR 1⋅39) and R2/unresected status (HR 3⋅50) were associated with decreased OS. In the R0/R1 subgroup, the 2-year RFS rate was similar for BD3 and BD1 + BD2 according to metastatic status. There was no significant difference between BD3 and BD1 + BD2 for change in tumour size in the R2/unresected subgroup (P = 0⋅094). Of 141 patients with initially unresectable metastases who had chemotherapy, 35 achieved conversion from unresectable to resectable status. The conversion rate was significantly higher for BD1 + BD2 than for BD3 (36 versus 18 per cent; P = 0⋅016). Conclusion: Stage IV colorectal cancer with high-grade tumour budding according to ITBCC criteria correlates with poor prognosis.

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Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial

Cited by 95 publications

References 31 publications

Intramural metastasis to the appendix from ascending colon cancer: a case report

Intramural metastasis to the appendix from ascending colon cancer: a case report

Immunohistochemical‑based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial‑mesenchymal transition

Prognostic and predictive values of tumour budding in stage IV colorectal cancer

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