T1期食管鳞状细胞癌组织肿瘤出芽与内镜分型及恶性程度的关系

目的 探讨T1期食管鳞状细胞癌组织中肿瘤出芽的临床病理意义。方法 在T1期食管鳞状细胞癌（SCC）切除组织中查找肿瘤出芽,并分析肿瘤出芽与内镜分型和各种病理参数之间的相关性,以验证肿瘤出芽是否可作为衡量浅表浸润性食管癌侵袭性的一项有用指标。结果 经表皮生长因子受体（EGFR）标记后肿瘤出芽检出率有明显提高（P<0.05）。肿瘤出芽检出率在T1b期食管SCC患者显著高于T1a期者,差异有统计学意义（P<0.05）;有淋巴结转移的病例肿瘤出芽检出率显著高于无转移者,差异有统计学意义（P<0.05）;ⅡB期者肿瘤出芽检出率显著高于ⅠB期,差异有统计学意义（P<0.05）。结论 肿瘤出芽在T1期食管SCC中检出率较高;EGFR免疫组织化学标记可提高食管SCC中肿瘤出芽的检出率;当T1期食管SCC出现肿瘤出芽时提示其更具侵袭性。     

肿瘤出芽和TILs与结直肠癌患者临床病理特征和预后的相关性北大核心

目的:研究不同数量及比例的肿瘤出芽(tumor budding,TB)、肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)在结直肠癌中的临床病理意义。方法:收集193例结直肠癌患者的肿瘤切片和临床资料,在HE染色下观察肿瘤出芽及TILs水平,并分析肿瘤出芽、TILs、出芽TILs联合分组与患者临床病理特征和预后的关系。结果:在结直肠癌患者中,肿瘤出芽与TNM分期、肿瘤解剖分期、分化程度、脉管侵犯、神经侵犯和预后相关(P<0.05);TILs与性别、TNM分期、肿瘤解剖分期、分化程度、神经侵犯、伴黏液腺癌和预后相关(P<0.05);出芽TILs联合分组与TNM分期、肿瘤解剖分期、分化程度、脉管侵犯、神经侵犯和预后相关(P<0.05),低出芽+高TILs组总生存期最长,高出芽+高TILs组次之,低出芽+低TILs组再次之,高出芽+低TILs组总生存期最短;肿瘤浸润淋巴细胞水平与肿瘤出芽水平呈负相关。结论:不同水平的肿瘤出芽、TILs、出芽TILs联合分组均能反映结直肠癌侵袭转移能力及预后,且出芽TILs联合分组相比肿瘤出芽和TILs对预后有更精细的评估。     

Tumor budding,a novel prognostic indicator for predicting stage progression in T1 bladder cancers

Tumor budding has been defined as an isolated single cancer cell or a cluster composed of fewer than five cancer cells scattered in the stroma. It is a strong predictor for lymph node metastasis in T1 colorectal cancer. We introduced this concept to T1 non‐muscle invasive bladder cancer and evaluated whether tumor budding could have a prognostic impact on the clinical outcome. We identified 121 consecutive patients with newly diagnosed T1 bladder cancer between 1994 and 2014 at Keio University Hospital. All slides were re‐reviewed by a dedicated uropathologist. Budding foci were counted under ×200 magnification. When the number of budding foci was 10 or more, tumor budding was defined as positive. The relationship between tumor budding and clinical outcomes was assessed using a multivariate analysis. The median follow‐up was 52 months. Tumor budding was positive in 21 patients (17.4%). Tumor budding was significantly associated with T1 substaging, tumor architecture and lymphovascular invasion. The 5‐year progression‐free survival rate in T1 bladder cancer patients with tumor budding was 53.8%, which was significantly lower than that in patients without tumor budding (88.4%, P = 0.001). A multivariate Cox regression analysis revealed that tumor budding was independently associated with stage progression (P = 0.002, hazard ratio = 4.90). In a subgroup of patients treated with bacillus Calmette‐Guérin instillation (n = 88), tumor budding was also independently associated with stage progression (P = 0.003, hazard ratio = 5.65). Tumor budding may be a novel indicator for predicting stage progression in T1 bladder cancer, and would likely be easily introduced in clinical practice.     

Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met

Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c‐Met protein expression and phosphorylation and MET gene copy numbers because c‐Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease‐free survival (DFS) from the low‐grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma.     

Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma.

BACKGROUND: In an earlier study, the authors demonstrated that tumor budding was useful for predicting lymph node metastasis in patients with early invasive (T1) colorectal carcinoma. This study was undertaken to clarify the associations between tumor budding, E-cadherin-catenin complex, and CD44 variant 6 abnormalities. METHODS: In 51 T1 colorectal carcinomas, tumor budding (the number of dedifferentiation units at the invasive margin) on hematoxylin and eosin-stained slides was counted under light microscopy. Immunostaining for E-cadherin, alpha-catenin, beta-catenin, and CD44 variant 6 was performed on formalin fixed, paraffin embedded sections. The associations between locoregional failure (lymph node metastasis or local recurrence) and tumor budding and clinicopathologic parameters and immunoreactivity were examined statistically. RESULTS: In univariate analysis, tumor budding and nuclear beta-catenin expression were associated significantly with locoregional failure (P = 0.004, 0.01). Multivariate analysis showed that tumor budding alone was associated significantly with locoregional failure (P = 0.02), and the association between nuclear beta-catenin expression and locoregional failure was marginally significant (P = 0.07). Analysis of variance showed that lymphatic invasion alone was associated significantly with tumor budding (P = 0.02), and there was a significant interaction effect for tumor budding between CD44 variant 6 expression and nuclear beta-catenin expression (P = 0.01). There was a significant correlation between expression patterns of these two molecules and locoregional failure (P = 0.01). CONCLUSIONS: The current results suggest that the up-regulation of CD44 variant 6 through nuclear beta-catenin activation may contribute to the formation of tumor budding, and immunostaining of these two adhesion molecules may be useful in identifying those at high-risk for locoregional failure among patients with T1 colorectal carcinoma.     

Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget

Epithelial mesenchymal transition (EMT) is proposed as a critical mechanism for the acquisition of malignant phenotypes by epithelial cells. In colorectal cancer, tumor cells having undergone EMT are histologically represented by the presence of tumor buds defined as single cells or small clusters of de-differentiated tumor cells at the invasive front. Tumor budding is not a static, histological feature rather it represents a snap-shot of a dynamic process undertaken by an aggressive tumor with the potential to disseminate and metastasize. Strong, consistent evidence shows that tumor budding is a predictor of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival time and an independent prognostic factor. Moreover, the International Union against Cancer (UICC) recognizes tumor budding as a highly relevant, additional prognostic parameter. The aim of this review is to summarize the evidence supporting the implementation of tumor budding into diagnostic pathology and patient management and additionally to illustrate its worthiness as a potential therapeutic target.     

联合肿瘤芽殖与淋巴管浸润预估大肠癌淋巴结转移的研究

目的 联合肿瘤芽殖与淋巴管浸润预估大肠癌淋巴结转移,旨在确立一组与大肠癌淋巴结转移密切相关的指标.方法 回顾性调查施行根治手术并具有完整临床病理资料的大肠癌病例168例,评价芽殖或与淋巴管浸润联合预估淋巴结转移的可行性.结果 肿瘤芽殖与淋巴结转移程度、数目、浸润深度、临床分期等病理生物学指标密切相关;肿瘤芽殖单独预测淋巴结转移的灵敏度、特异性、阳性预测值、阴性预测值分别为:86%、45%、49%、84%;而联合淋巴管的预测灵敏度、特异性、阳性预测值、阴性预测值分别为:88%、44%、49%、85%.结论 术前通过超声纤维结肠镜和螺旋CT的准确判断,结合肿瘤芽殖这一病理生物学指标预估伴发淋巴结转移的风险,对选择个体化的合理治疗方案具有非常重要的实践意义.     

肿瘤出芽计数在预测T1期结直肠癌淋巴结转移中的应用价值

背景与目的：肿瘤出芽是结直肠癌的不良预后因素。本研究使用10个高倍镜视野计数的方法评价肿瘤出芽,并分析其在预测T1期结直肠癌淋巴结转移中的临床应用价值。方法：通过计数307例T1期结直肠癌10个高倍镜视野下肿瘤出芽个数,参比临床病理特征,建立T₁期结直肠癌淋巴结转移的风险分析公式,并在14例新病例中对该公式进行验证。结果：多因素分析结果显示,肿瘤分化水平、脉管侵犯和肿瘤出芽个数与T₁期结直肠癌淋巴结转移显著相关。统计分析得出的淋巴结转移的风险分析公式为：Z=1.571×(脉管状态：侵犯为1;无侵犯为0)+2.661×(肿瘤分化：高级别为1;低级别为0)+0.024×(肿瘤出芽个数)-3.885,概率=1/1+e^-Z。在14例新病例中得到了验证。结论：通过计数10个高倍镜视野下的肿瘤出芽个数,可以精确地评估淋巴结转移风险,从而协助临床作出合理的决策。     

Prognostic significance of tumor budding in gastrointestinal tumors

Tumor budding describes the presence of single tumor cells or small tumor cell clusters at the invasion front of carcinomas. It is currently thought to be the result of epithelial-mesenchymal transformation. Tumor budding can be appreciated histologically during routine evaluation of malignant polyps or surgical specimens of malignant tumors. Many studies have been published assessing cancers in all locations from the esophagus to the rectum, almost always reporting similar results. This seems especially remarkable as a generally accepted definition of how budding must be evaluated is still lacking. Regardless of the location, tumor budding generally is associated with nodal metastases and aggressive behavior, and it is mostly independent from other adverse factors. While the prognostic value of tumor budding is evident, especially in stage II colorectal cancers, it still has no therapeutic implications. This is owing to the heterogeneity of the performed studies and the lack of oncological studies, which are urgently needed.     

Prognostic significance of tumor budding in gastrointestinal tumors

Tumor budding describes the presence of single tumor cells or small tumor cell clusters at the invasion front of carcinomas. It is currently thought to be the result of epithelial–mesenchymal transformation. Tumor budding can be appreciated histologically during routine evaluation of malignant polyps or surgical specimens of malignant tumors. Many studies have been published assessing cancers in all locations from the esophagus to the rectum, almost always reporting similar results. This seems especially remarkable as a generally accepted definition of how budding must be evaluated is still lacking. Regardless of the location, tumor budding generally is associated with nodal metastases and aggressive behavior, and it is mostly independent from other adverse factors. While the prognostic value of tumor budding is evident, especially in stage II colorectal cancers, it still has no therapeutic implications. This is owing to the heterogeneity of the performed studies and the lack of oncological studies, which are urgently needed.     

Tumor budding as a useful prognostic marker in T1‐stage squamous cell carcinoma of the esophagus

Background

Establishing a new prognostic factor for early‐stage cancer may seem difficult due to the small number of disease‐specific deaths. Tumor budding has been recognized as a useful microscopic finding reflecting biological activity of the tumor.

Methods

Tumor budding stand for isolated single cancer cells and cell clusters scattered beyond the tumor margin at the invasive front. It was searched for in the resected esophagus with T1 squamous cell carcinoma (SCC), and the correlation between the tumor budding, patient survival, and various pathologic factors were analyzed to verify whether tumor budding is a prognostic factor in superficial esophageal cancer.

Results

Seventy‐nine patients undergoing curative esophagectomy were assigned to frequent (n = 29) and rare (n = 50) groups according to the microscopically observed frequency of tumor budding in the tumor. Three‐year survival rates after esophagectomy were 48.8% for the frequent group and 94.5% for the rare group. Multivariate analysis using the Cox proportional hazards model identified this morphological variable as a significant independent prognostic factor.

Conclusions

Tumor budding reflects the biological activity of the tumor and may be a useful prognostic indicator even in early‐stage SCC of esophagus. J. Surg. Oncol. 2013;108:42–46. © 2013 Wiley Periodicals, Inc.     

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy

BACKGROUND:

In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.

METHODS:

Studied were 74 patients who received neoadjuvant chemotherapy (5‐fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival.

RESULTS:

Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high‐grade budding in the invasive front. The 5‐year survival rate of patients with low‐grade budding tumors was 49%, compared with 17% for those with high‐grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases.

CONCLUSIONS:

The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified. Cancer 2009. © 2009 American Cancer Society.     

结直肠癌雌激素受体、孕激素受体、C-erbB-2表达与肿瘤芽的关系

 目的　探讨在结直肠癌雌激素受体（ER）、孕激素受体（PR）、C-erbB-2表达与肿瘤芽（budding）的关系。方法　对93份存档大肠癌石蜡组织标本进行重新切片，采用免疫组织化学染色法分别检测ER、PR、C-erbB-2在大肠癌标本的表达。染色结果与结直肠癌常规染色标本肿瘤芽进行比较。结果　ER、C-erbB-2在大肠癌标本的表达与结直肠癌肿瘤芽正相关，而PR与肿瘤芽呈负相关。结论　检测PR、C-erbB-2对准确判断结直肠癌生物学行为有所帮助。ER与肿瘤芽的关系还有待进一步研究。     

TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer

Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding phenotype. TWIST1 and TWIST2 promoter methylation and protein expression were investigated in six cell lines and further correlated with tumor budding in patient cohort 1 (n = 185). Patient cohort 2 (n = 112) was used to assess prognostic effects. Laser capture microdissection (LCM) of tumor epithelium and stroma from low- and high-grade budding cancers was performed. In colorectal cancers, TWIST1 and TWIST2 expression was essentially restricted to stromal cells. LCM results of a high-grade budding case show positive TWIST1 and TWIST2 stroma and no methylation, while the low-grade budding case was characterized by negative stroma and strong hypermethylation. TWIST1 stromal cell staining was associated with adverse features like more advanced pT (p = 0.0044), lymph node metastasis (p = 0.0301), lymphatic vessel invasion (p = 0.0373), perineural invasion (p = 0.0109) and worse overall survival time (p = 0.0226). Stromal cells may influence tumor budding in colorectal cancers through expression of TWIST1. Hypermethylation of the tumor stroma may represent an alternative mechanism for regulation of TWIST1.     

Tumor budding and human chorionic gonadotropin-β expression correlate with unfavorable patient outcome in colorectal carcinoma

Tumor budding is thought to represent a manifestation of epithelial-to-mesenchymal transition (EMT) and it has been correlated with poor patient outcomes in colorectal cancer (CRC). Our group recently demonstrated that human chorionic gonadotropin-β (hCGβ) modulates EMT in CRC. In the current study, based on the likely relationships between tumor budding and hCGβ expression, we examined their clinicopathologic significance in CRC. Twenty-eight of 80 (35.0%) CRC showed tumor budding. Tumor budding significantly correlated with lymph node metastasis (P?<?0.01), pathologic stage (P?<?0.01), lymphatic invasion (P?=?0.044), and vascular invasion (P?=?0.013). Thirteen of 80 (16.3%) CRC were hCGβ positive on immunohistochemistry. More tumor buds were present in the hCGβ-positive cases (P?<?0.01), and tumor budding was significantly correlated with hCGβ positivity (P?<?0.01). Cases with both tumor budding and hCGβ expression had the poorest prognosis compared with all other groups (P?<?0.01). In conclusion, tumor budding and hCGβ expression are closely associated with EMT, and they are independent prognostic factors in CRC. They identify patients with an “EMT phenotype” who may respond to targeted molecular therapies.     

The prognostic role of tumor budding and tumor-stroma ratio in pulmonary metastasis of colorectal carcinoma

ObjectiveTo evaluate the prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC).MethodsIn total, 106 pulmonary metastasectomies were performed to 74 patients in two study hospitals during 2000–2020. All relevant clinical data were retrospectively collected. Tumor budding based on the International Tumor Budding Consensus Conference recommendations and TSR in the first resected pulmonary metastases and primary tumors were evaluated from diagnostic hematoxylin-eosin-stained histopathological slides.Results60 patients (85.7%) had low tumor budding (≤5 buds/field) and 10 patients (14.3%) had high tumor budding (>5 buds/field) in their first pulmonary metastases of CRC. 5-year overall survival rates of pulmonary metastasectomy in low and high total tumor budding were 28.3% and 37.3% (p = 0.387), respectively. 19 patients (27.1%) had low TSR and 51 patients (72.9%) had high TSR. The 5-year overall survival rates were 32.9% in low and 28.6% in high TSR of first pulmonary metastases (p = 0.746). Tumor budding and TSR did not provide prognostic value in Cox multivariate analysis. Tumor budding and TSR in resected pulmonary metastases were not associated with those of the primary tumor.ConclusionTumor budding and TSR in the resected pulmonary metastases of CRC showed no statistically significant prognostic value, however, additional well-powered confirmatory studies are needed.     

Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung

Tumor budding is morphologically defined as infiltration by small clusters of cancer cells. While the biological properties of budding cells in adenocarcinoma (decreased expression of adhesion molecules and of differentiation markers) have been elucidated, those of the cells in squamous cell carcinoma (SqCC) of the lung still remain to be clarified. We examined the clinicopathological data of 217 patients with SqCC of the lung. Furthermore we evaluated the immunohistochemical properties of the budding cells. Tumor budding was observed in 83 (38.2%) patients. A statistically significant difference was observed in overall 5-year survival rates between the cases showing tumor budding and the cases not showing budding (45.6% vs. 64.0%, p<0.001). As compared with cancer cells forming solid nests, budding cells (BCs) exhibited reduced expression levels of the cellular adhesion molecules (E-cadherin; p=0.004, β-catenin; p=0.002) and increased expression levels of laminin-5γ2 (p=0.001). On the other hand, no significant differences in the staining scores for differentiation markers (p63 and podoplanin) were found between BCs and cancer cells forming nests. Multivariate analysis revealed that tumor budding was a significant independent prognostic factor in patients with SqCC of the lung (p=0.022). Tumor budding is an independent adverse prognostic factor in patients with SqCC of the lung. Although budding cells in SqCC exhibited reduced expression levels of the cellular adhesion molecules, the expression levels of specific differentiation markers were retained, suggesting that the budding mechanism in SqCC may differ, at least in part, from that in adenocarcinoma.     

Prognostic significance of tumor budding in biliary tract cancer

BackgroundTumor budding is a significant prognostic indicator for poor survival of several solid tumors. However, due to the lack of a standard scoring system, its clinical application for biliary tract cancer (BTC) is limited.ObjectiveTo identify the prognostic significance of tumor budding in BTC.ResultsTumor budding was associated with poor histologic differentiation, lymphovascular invasion, perineural invasion, lymph node metastasis, positive surgical margin, etc. Tumor budding was a predictor of poor OS in univariate (HR: 4.36; 95% CI 3.15 to 6.02; P < 0.001) and multivariate (HR: 2.95; 95% CI 2.28 to 3.80; P < 0.001) analysis. Similarly, it was also a predictor of poor DFS in univariate (HR: 3.26; 95% CI 2.12 to 4.99; P < 0.001) and multivariate (HR: 3.21; 95% CI 1.90 to 5.40; P < 0.001) analysis. In addition, tumor budding was also associated with advanced T-stage, poor histologic differentiation, lymph node metastasis, positive resection margin, lymphatic invasion, vascular invasion, and perineural invasion.ConclusionResults of our study have shown that tumor budding is a strong predictor of poor survival for BTC. The clinical utility of tumor budding as a prognostic marker for BTC should be considered after developing a standard international consensus based on the current evidence.     

Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Invasive tumor front (ITF) is the deepest three to six cell layers or detached tumor cell groups at the advancing edge of the tumor. Tumor budding is defined as presence of isolated single cells or small cell clusters scattered in the stroma ahead of the ITF and is characteristic of aggressive cancer. It is recognized as an adverse prognostic factor in several human cancers like colorectal, oesophageal, laryngeal cancers and more recently tongue cancers. However, the prognostic value of tumor budding has not been reported in GBCSCC. The aim of our study was to evaluate the role of pattern of invasion (POI) at the ITF, Tumor budding and other clinicopathological parameters in predicting nodal metastases and prognosis in GBCSCC. 33 patients with primary GBCSCC were prospectively evaluated at a tertiary care referral centre. Tumor budding and type of POI was examined in detail and data documented. Statistical analyses were carried out to assess the correlation of tumor budding, POI, and other clinicopathologic parameters (stage, grade of the tumor, tumor thickness, PNI, LVI) with nodal metastases and predict prognosis. Cox regression was used for both Univariate and multivariate analysis. Significant predictors of nodal metastases on Univariate analysis were male gender (p = 0.021), smoking (p = 0.046), Tumor budding (p = 0.014) and diffuse infiltrative/worst POI (p = 0.004), where as on multivariate analysis only worst POI was significantly associated with positive lymph nodes (p = 0.004). Presence of nodal metastases (p = 0.01) and tumor thickness >5 mm (p = 0.009) were independent negative prognostic factors on multivariate analysis. Significant single risk factor predictive of positive lymph nodes is worst POI in GBCSCC. Nodal metastases and >5 mm tumor thickness are independent risk factors for disease free survival.     

Histopathological Significance and Prognostic Impact of Tumor Budding in Colorectal Cancer

Background: Colorectal cancer (CRC) is a heterogeneous disease with a complex etiology. New prognostic factorsneed to be investigated. Our present focus is on histopathological significance and prognostic impact of tumor buddingin CRC. Material and Methods: A total of 60 treatment-naive consecutive patients undergoing surgical resection ofCRCs during the period of January 2011 to December 2013 were included in the study. Details of each related to theirdemographic and tumor profile were recorded. Hematoxylin and Eosin (H and E) and pan-cytokeratin details of each“case” immunohistochemically stained sections were examined for tumor budding assessment along with clinicalfeatures. Results: The most frequent site of involvement was the rectosigmoid and sigmoid colon (31.6%). The majorityof the cases were moderately differentiated (75%), showed tumor invasion into the pericolic/subserosal fat (66.6%) andstage III (38.3%). Nodal involvement was present in 47%. Correlations between tumor budding and nodal involvement(p-value 0.039) and AJCC stage (p-value 0.021) were found to be statistically significant. Conclusion: Tumor buddingis a promising and powerful predictor of lymph nodal metastasis and a higher stage of tumor and can be used as amarker for high-risk CRC. Routine H and E staining aided by cytokeratin immunostaining allows reproducible gradingof tumor budding in CRC cases.