Clinical significance of tumor budding as a marker for predicting distant metastasis after radical gastrectomy in elderly patients / 中华老年医学杂志

Objective:To investigate the clinical significance of tumor budding as an indicator of postoperative distant organ metastasis after radical gastrectomy in elderly patients diagnosed with gastric cancer.Methods:The clinical and pathological data of 124 elderly patients who experienced metastasis after undergoing radical gastrectomy were retrospectively analyzed.The analysis was conducted from March 2015 to June 2022, focusing on the clinicopathological factors that influenced the occurrence of postoperative distant metastasis in these patients.Tumor budding in gastric cancer tissues was assessed using hematoxylin-eosin staining, and its clinical significance was analyzed.Results:The tumor budding grade of gastric cancer tissues showed a significant correlation with vascular invasion( χ2=6.731, P=0.009), the number of lymph node metastases( rs=0.481, P<0.001), and the time of distant metastasis( rs=-0.450, P<0.001).In the univariate analysis, factors such as tumor budding grade, tumor size, vascular invasion, postoperative chemotherapy, cancerous nodule, preoperative serum carbohydrate antigen 125, and the number of lymph node metastases were found to influence distant metastasis-free survival after radical gastrectomy in elderly patients(all P<0.05).The multifactorial analysis also indicated that tumour outgrowth grade was an important independent prognostic factor for postoperative distant metastasis in elderly gastric cancer patients( HR=3.731, P<0.001). Conclusions:The findings of this study indicate that tumor budding may serve as a potential marker for predicting distant organ metastasis in elderly patients who have undergone radical gastrectomy.This discovery holds significant clinical implications.

Study of tumor budding and its association with clinicopathological parameters in breast carcinoma

SUMMARY OBJECTIVE: Tumor budding is a phenomenon in which the tumor cells detach from the main mass and are present at the invasive front. The present study was conducted to study tumor budding in invasive breast carcinoma and to correlate it with clinicopathological parameters and molecular subtypes. METHODS: The study was conducted over a period of 1 year, and tumor budding was studied as a single or group of cells at the invasive front of breast carcinoma counted in a high-power field (40×). The grading was statistically correlated with tumor size, grade, lymph node status, lymphovascular invasion, pathological TNM staging, molecular subtype, and survival of patients. RESULTS: A total of 50 cases of invasive breast carcinoma were included, out of which 66% (n=33) showed high-grade tumor budding, which was statistically significantly higher in grade 2 invasive ductal carcinoma (p<0.05). High tumor budding was associated with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. All cases showing low-grade budding were alive until 6 months of diagnosis, but there was no statistically significant association between stage and budding. CONCLUSION: Tumor buds are significantly higher in grade 2 invasive ductal carcinoma with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. Immunohistochemistry may prove helpful in distinguishing tumor buds from their mimickers. Further studies with extended follow-up are recommended to predict tumor budding as a prognostic marker in breast carcinoma, which may play an important role in cancer therapy.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.

Evaluation and prognostic significance of tumor budding in pancreatic ductal adenocarcinomas

Aim: In this study, it was aimed to investigate the prognostic importance of Tumor budding (TB) in Pancreatic ductal adenocarcinomas(PDAC) and its correlation with histopathological findings according to the International Tumor Budding Consensus Conference(ITBCC) grading. Material and Methods: A total of 75 patients diagnosed with PDAC were included in this study. The demographic features of the cases (age, sex) and the macroscopic features of the tumors (localization,size) were obtained from the electronic archive system. All Hematoxylin-Eosin-stained sections were re-evaluated in terms of differentiation, presence of lymphovascular (LVI) and perineural invasion(PNI), surgical margin positivity, primary tumor(pT), lymph node metastasis(LNM) and tumor budding. Statistically, Chi-square test, cox-regression and Kaplan-Meier test were performed. Results:Thirty four of the cases were female and 41 were male. The mean age was 64.21±9.71years. The degree of TB was TB-few in 17 cases, TB-moderate in 25cases, and TB-high in 33cases. LVI, PNI, LNM and TB-high were poor prognostic factors. Moreover, TB-high was related with poor differantiation,LVI,PNI,LNM and short survival time. Tumor budding was independent negative prognostic factor in multivariable model analyzes. Conclusion: ITBCC scoring can also be used in PDACs. In addition, high tumor budding was a poor prognostic feature and might be a target for tumor-specific treatments as it could be a predictive finding for the locally invasive character of the tumor. Evaluation and grading of TB thought to represent EMT may be a histological feature that can be used in tumor selection for advanced molecular methods to identify subtypes that may be associated with poor prognosis and drug resistance.

Evaluation of tumor budding and its correlation with histomorphological prognostic markers in oral squamous cell carcinoma and its association with the epithelial-mesenchymal transition process

Objective: To evaluate the association of tumor budding (TB) with prognostic histomorphological parameters in oral squamous cell carcinoma (OSCC) and to investigate the correlation of TB intensity with epithelial to mesenchymal transition (EMT). Material and Method: A total of 200 cases diagnosed as OSCC were selected and their TB status was reviewed using Hematoxylin and eosin (H and E) and Immunohistochemistry (IHC). Correlation with histomorphological prognostic parameters was done. Also, IHC for Vimentin and E-cadherin was performed to look for EMT. Results: On H and E examination, TB was observed in 154/200 (77%). About 88/154 (57.14%) cases showed a high TB (>5 TB/10 hpf) which increased to 100/154 (64.9%) cases on IHC staining. The intensity of TB was significantly associated with tumor grade and depth of invasion. It was also significantly associated with reduced expression for E-Cadherin and upregulation of Vimentin establishing a pathogenetic correlation between the TB and EMT. Conclusion: Therefore, our results suggest that TB is associated with poor prognosis and histologically represents EMT in OSCC which further adds to the aggressiveness of the tumor.

Correlation of tumor budding with KRAS,NRAS,BRAF gene mutation and MSI status in colorectal adenocarcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To explore the clinicopathological re-lationship between tumor budding and KRAS,NRAS,BRAF gene mutations and MSI status in colorectal adenocarcinoma and their clinical significance.Methods The clinical data of 237 cases of colorectal adenocarcinoma were collected to interpret tumor budding.RT-PCR was used to detect the gene mutations of KRAS,NRAS,BRAF in 229 cases and to analyze the corre-lation between tumor budding and gene mutations.MSI was de-tected by PCR and its relationship with tumor budding was ana-lyzed.Results Of the 237 patients,147 showed low-to medi-um-grade tumor budding and 90 showed high-grade tumor bud-ding.Tumor budding was associated with tumor size,vascular involvement,perineural invasion,tumor differentiation,lymph node metastasis,tumor nodule formation,tumor recurrence and TNM staging(P＜0.05),while it was not associated with age,sex and location.Single factor logistic regression analysis showed that tumor budding was associated with the risk of lymph node metastasis(P＜0.05),while multivariate logistic regres-sion analysis showed that tumor budding was an independent pre-dictor of lymph node metastasis in colorectal adenocarcinoma(P＜0.05).Of the 229 cases,the mutation rate of KRAS,NRAS and BRAF was 42.4％,2.6％and 3.1％,respectively.A-mong KRAS,NRAS and BRAF mutation cases,the proportion of high-grade tumor budding was 56.7％,33.3％and 14.3％,respectively.Tumor budding was associated with mutations in the Kras 12 and Kras 13 codons,as well as KRAS total muta-tions(P＜0.05).However,tumor budding had no relationship with NRAS and BRAF.In the high-grade budding tumors,KRAS mutations were mainly KRAS codons 12 and 13.Among the cases with KRAS mutation,the disease-free survival time and total survival time of the cases with high-grade tumor bud-ding were significantly shorter(P＜0.05).Of the 237 patients,the rate of MSI-H was 6.8％and only 2 out of 16 MSI-H pa-tients had high-grade tumor budding.There was a negative cor-relation between tumor budding and MSI status(r=-0.143,P＜0.05).Conclusion Tumor budding is related to the muta-tions in the Kras 12 and Kras 13 codons,as well as total KRAS mutations and MSI status.Tumor budding is also related to the prognosis of patients with colorectal adenocarcinoma,which can provide a reference for their outcome judgment.

Association of tumor budding in preoperative biopsies with clinicopathological characteristics and prognosis of colorectal cancer / 临床与实验病理学杂志

Purpose To explore the association of tumor budding in preoperative biopsies with the clinicopathological characteristics of colorectal cancer(CRC),and its effects on the prognosis.Methods A total of 144 preoperative biopsies and corresponding radical resection specimens of colorectal ade-nocarcinoma were collected.Tumor budding was evaluated by HE staining and EnVision immunohistochemical staining,to an-alyze the association of tumor budding with the clinicopathologi-cal characteristics and prognosis in biopsies.Results The de-tection rate of intra-tumoral budding(ITB)in biopsy specimens was 39.6%(57/144),and peritumoural budding(PTB)in surgical specimens was 64.6%(93/144);ITB was significantly correlated with PTB(r =0.510,P<0.05).The proportion of patients with lymph node metastasis,pTNM stage,differentiated degree,vascular invasion and nerve recidivism in the tumor bud-ding group of biopsies was significantly higher than that in no tumor budding group(P<0.05).Kaplan-Meier survival analy-sis showed that ITB significantly affected the overall survival and progression free survival of CRC(P<0.05).Conclusion The presence of ITB in biopsies tissue may be an important indicator of invasive behavior and poor prognosis in CRC.

Tumor budding is a valuable prognostic parameter in endometrial carcinomas

Background: Tumor budding (TB) is a morphological finding believed to play an important role in determining the prognosis in many cancers. Aim: Our aim is to evaluate the prognostic importance of TB in endometrial carcinomas. Settings and Design: Two-hundred-eleven endometrial cancers were obtained from 2008 to 2015 that were comprised of those having undergone surgical staging with a hysterectomy and at least 5 years followed up. Material and Methods: All hematoxylin and eosin stained slides were reevaluated for the status of TB. Statistical Analysis: Nonparametric tests, the Kaplan–Meier method, the Log-rank test, and Cox proportional hazard regression were used. Results and Conclusion: TB was found to correlated with larger diameter (P = 0.000), nonendometrioid (P = 0.038), mixed cell types (P = 0.005), higher grade (P = 0.000), deeper invasion of the myometrium (P = 0.000), cervical stromal invasion (P = 0.000), advanced pT (P = 0.011), lymph node involvement (P = 0.000), lymphovascular invasion (P = 0.000), and advanced stage (P = 0.000). The presence of TB worsens the 5-year overall survival (OS) (P = 0.0001). In cases such as grade 1, pT1, or stage 1 endometrial carcinomas, the presence of TB decreases the OS rate (P = 0.00017, P = 0.0016, P < 0.0001). Our result suggested that the presence of TB adversely affects the prognosis. It was concluded that TB could be a valuable prognostic parameter.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups – Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades.Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

The Role of Tumour Budding as a Prognostic Factor in Primary Invasive Ductal Carcinoma of Breast.

Background: Tumor budding is considered as an essential step in invasion and as a poor prognostic factor in carcinoma.It is used as the main prognostic factor in colon cancer but it is now gaining popularity in other tumor types. Objectives of the study was to determine tumor budding and categorize it into low grade and high grade in primary invasive breast cancer patients and to determine the association of tumor budding with clinicopathological characteristics. An attempt was also made to compare cytokeratin expression in intra- tumoral and budding sites. Method: It was an observational-analytical study including 50 cases of surgically resected modified radical mastectomy specimens diagnosed as invasive breast carcinoma in the tertiary care hospital from October 2018 to March 2020. Tumor buds were counted in H&E and IHC stained sections in 10 high power fields. IHC marker used was pan cytokeratin. Cases were classified into low tumor budding and high tumor budding. Correlation of tumor budding was done with all the established clinicopathological characteristics. Cytokeratin expression was compared in tumor proper and budding sites. Results: Among the 50 casesof invasive breast carcinoma, 24 cases showed high tumor budding (>4/10HPF) and 26 cases showed low tumor budding (?4/10HPF). High tumor budding was seen with larger size of the tumor, higher primary tumor staging, higher lymph node staging, presence of lymphovascular invasion, lymph node involvement and presence of necrosis with a significant correlation. Also cytokeratin expression was similar in tumor proper and budding sites in 92% of the cases. Interpretation & Conclusion: Tumor budding showed significant correlation with tumor size, primary tumor staging, lymph node staging, lymph node involvement, lymphovascular invasion and tumor necrosis. Thus it can be considered as a significant prognostic factor in the invasive breast carcinoma and can be incorporated in the reporting protocol for breast cancer.

High tumor budding activity may predict poor prognosis in laryngeal squamous cell carcinomas

Background: Laryngeal squamous cell carcinoma (SCC) which is the most common carcinoma of the respiratory system after lung carcinomas is graded by the World Health Organization (WHO) into three groups as grades 1, 2, and 3. This system does not correlate with the prognosis and has a low reproducibility among the pathologists. Searching for a new grading system, in this study, we investigated the relationship between tumor budding and histomorphological parameters and survival status. We examined the new grading system based on cell nest size and tumor budding. Methods: Partial and total laryngectomy materials of 130 patients diagnosed as laryngeal SCC between 2012 and 2018 in our clinic were evaluated retrospectively by two pathologists. Tumor budding activity and cell nests were scored and a new score was obtained by summing the scores. According to the scores obtained, a new grading system was created. Results: There was a statistically significant difference between the tumor budding activity and the overall and disease-free survival times of the groups. The overall and disease-free survival time of the patients with high tumor budding significantly reduced. Tumor budding was found to be low in the presence of an intense lymphocytic host response (P < 0.05). There was no relationship between the new grade system and cell nest size and life expectancy (P > 0.05). Conclusions: Tumor budding provides significant clues in predicting the life expectancy of the patients. Therefore, tumor budding might be a component of new grading systems and should take place in pathology reports.

Histopathological study of tumor budding in colorectal carcinoma and its correlation with clinicopathological parameters

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. “Tumor budding,” defined by the presence of five or less tumor cell cluster in the invasive front of tumor, is a strong, reproducible, and independent prognostic marker of the biological aggressiveness of the tumor. Aim and Objective: The present study was conducted to assess the correlation of clinicopathological parameter with tumor budding in CRC. Materials and Methods: Sixty patients presenting with colectomy specimens with known histological diagnosis of colorectal adenocarcinoma were included in the study. Histological examination with hematoxylene and eosin stain and immunohistochemistry with pancytokeratin (Pan-CK) was performed in equivocal cases. Tumor budding was counted and scored as per international tumor budding consensus conference, 2016, recommended criteria. Tumor budding was correlated with other relevant clinicopathological parameters. Results: The age distribution ranged from 19 to 78 years with a peak incidence in the age group of 41–50 years (31.7%). Low-grade tumor budding was seen in 20%, intermediate grade budding in 16.7%, and high-grade tumor budding in 63.3%. No correlation could be established between age, sex, site, size of tumor, lymphovascular invasion, histological grade, and budding intensity. However, association between tumor budding and nodal involvement, perineural invasion and higher American Joint Committee on Cancer stage has been found to be statistically significant in this study. Conclusions: Tumor budding is emerging to be a promising and powerful predictor of nodal metastasis and a higher stage of the tumor. Immunohistochemistry with Pan-CK can aid in the grading of tumor budding and buid consensus.

Clinicopathological Significance of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma / 肿瘤防治研究

Objective To investigate the clinicopathological significance of PDC in liver metastases and analyze the correlation of PDC between liver metastases and primary lesions. Methods Retrospective analysis of 72 matched cases of colorectal cancer with liver metastases was performed. The PDC in primary tumor and liver metastatic lesion was interpreted synchronously, and then the relationship between PDC in liver metastasis and clinicopathological parameters was analyzed based on the correlation of PDC between primary and metastatic lesions. In addition, PDC were interpreted in accordance with Uenos' standard. Results Among the 72 cases of liver metastasis of colorectal cancer, the number of G1, G2, and G3 graded by PDC was 28, 24, and 20, respectively. The PDC in liver metastatic lesion was correlated with tumor budding in liver metastatic lesion and PDC grade of primary lesion. No significant correlation with the size and number of liver metastatic lesion, the site, WHO grade, depth of invasion, lymph node metastasis, vascular invasion or tumor budding of the primary lesion was observed. Conclusion A positive correlation is found between liver metastasis of colorectal adenocarcinoma and PDC grade of primary tumor. Evaluating the PDC grade of primary tumor may provide a reference for the risk of liver metastasis.

Tumor budding is related with clinicopathology and prognosis of pancreatic neuroendocrine tumors / 中华普通外科杂志

Objective:To investigate the value of tumor budding in the clinicopathology and prognosis of pancreatic neuroendocrine tumors.Methods:The Cliniccal data of 105 pancreatic neuroendocrine tumor patients underwent resection in Henan Provincial People's Hospital from Jan 2010 to Dec 2016 were retrospectively analyzed. Tumor budding was calculated through hematoxylin-eosin (HE) and immunohistochemical stained slides. Based on the receiver operating characteristic curve (ROC), the number of tumor budding ≥10 was defined as the high-grade budding group, and <10 as the low-grade budding group. Multiple analysis was performed to determine the relationship between tumor budding and clinicopathology as well as prognosis.Results:High-grade budding group was observed in 35 cases and low-grade group in 70. High-grade budding were more common in tumors with advanced T stage, high risk of lymphatic metastasis, preoperative liver metastasis, vascular invasion and postoperative recurrence (respectively χ 2=9.043, 4.286, 10.130, 12.090, 9.260, all P<0.05). Multivariate COX regression analysis showed that tumor budding ( P=0.018), tumor grade ( P=0.026), preoperative liver metastasis ( P=0.042), vascular invasion( P=0.048) was independent risk factors predicting poor prognosis. Conclusion:Tumor budding is highly correlated with clinicopathological parameters which reflect the aggressiveness of pancreatic neuroendocrine tumor, it is also an important prognostic factor.

Radical surgery for colon cancer guided by membrane anatomy theory / 中华胃肠外科杂志

Like other solid tumors, colon cancer surgery has undergone a century-old journey from lumpectomy to organ resection and then to lymphadenectomy. From the Toldt fascia to complete mesenteric resection, and from local resection to D3 radical treatment, local recurrence rates have been reduced, but remain a nuisance to surgeons and patients. Based on the theory of membrane anatomy, radical surgery for colon cancer will focus more on removing the mesocolon from the mesentery bed while maintaining the integrity of the posterior fascia to avoid the occurrence of "fifth metastasis" as much as possible. Thanks to the membrane anatomy theory, its strong reproducibility and replicability, a new phase of colorectal surgery is on the horizon.

Relation Between Tumor Budding and Endoscopic Classification, Degree of Malignancy in T1 Stage Esophageal Squamous Cell Carcinoma / 肿瘤防治研究

Objective To investigate the clinical pathological significance of tumor budding in T1 stage esophageal squamous cell carcinoma. Methods Tumor budding was searched for in the resected tissues of T1 stage esophageal squamous cell carcinoma(ESCC), and the relation between tumor budding and endoscopic classification, degree of malignancy in T1 ESCC were analyzed. Results The detection rate of tumor budding was significantly improved after EGFR labeling(P < 0.05). The detection rate of tumor budding in T1b ESCC was significantly higher than that of T1a SCC(P < 0.05). The detection rate of tumor budding in the cases with lymph node metastasis was significantly higher than that without lymph node metastasis(P < 0.05). The detection rate of tumor budding in stage ⅡB ESCC was significantly higher than those with stageⅠB(P < 0.05). Conclusion The detection rate of tumor budding in T1 ESCC is relatively high. The detection rates of tumor budding is improved by EGFR immunohistochemistrical labeling. The occurrence of tumor budding in T1 ESCC indicates more tumor aggression.

CD57 as a routine neuroendocrine marker for liver metastasis

Background: The characterization of hepatic metastases as having neuroendocrine origins is essential and the main markers currently used are chromogranin A (CgA) and synaptophysin (Syn). However, these markers may exhibit certain limitations, and the use of CD56 and CD57 can also be considered, although, due to low specificity, their use is discouraged. Aim: This study sought to compare the immunohistochemical expression of these markers in hepatic metastases of neuroendocrine neoplasms (NEN). Materials and Methods: Eighteen samples, were used for immunohistochemical staining with CgA, Syn, CD56, and CD57 antibodies. The immunostaining reactions were compared according to its intensity (I), the percentage of labeled cells (P), and a final score (I × P). Statistical agreement between the markers was also evaluated. Results: CD57 was expressed in the highest number of cases and also showed the most intense expression. CgA showed the highest number of cases with more than 80% positively stained area (72.2%), followed by CD57 (61.1%). The highest average score (I × P) was obtained for CD57 (9.1 ± 4.1). The best indices of agreement were between CgA and CD57 with respect to positivity (P = 0.021) and score (P = 0.014). According to the primary site, stomach/duodenum, lungs, and undetermined subgroups showed the highest average scores for CD57, followed by CgA. For the small bowel subgroup, the highest average score was obtained for CgA, followed by CD57. Conclusion: Our results highlight the importance of CD57 in the evaluation of hepatic metastases of NEN and indicate that this marker should be included with CgA and Syn in routine diagnostic panels.

The role of tumor budding in colorectal adenocarcinoma: Possible involvement of the intestinal cancer stem cell marker Lgr5

Background: Tumor budding (TB) is a promising prognostic factor in colorectal cancer (CRC) that is independent of tumor-node-metastasis (TNM) staging. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a stem cell marker and a member of the canonical Wnt-signaling cascade. It is involved in colorectal carcinogenesis. However, its role in CRC progression and TB needs to be clarified. Materials and Methods: TB was assessed in both H and E and CK immunostained sections of 92 CRC cases. Associations between TB grade and different clinicopathological parameters were evaluated. Lgr5 expression in CRC cases and its association with TB grade and other clinicopathological features was also evaluated. Results: H and E stained sections revealed low- and high-grade budding in 55 (59.8%) and 37 (40.2%) tumors, respectively, whereas Cytokeratin Immunohistochemistry (CK-IHC) showed low- and high-grade budding in 31 (33.7%) and 61 (66.3%) tumors, respectively. TB grade (in H and E and CK stained sections) was significantly associated with adverse pathological prognostic variables including vascular invasion (P = 0.03 and 0.001), lymph node metastasis (P = 0.001 and 0,001), advanced Dukes (P = 0.000 and 0.000), and TNM (P = 0.001 and 0.000) stages and inversely associated with Tumor infiltrating lymphocytes (TILS) (P = 0.02 and 0.0001) which is known to be a good prognostic indicator. Lgr5 protein was positively expressed in 52.2% (48/92) of the CRCs. Immunoreactivity of Lgr5 was significantly associated with histological grade (P = 0.01), lymph node metastasis (P = 0.002), vascular invasion (P = 0.02), TNM stage (P = 0.000), Dukes stage (P = 0.000), and TILS (P = 0.03). Furthermore, Lgr5 was found to be significantly associated with TB estimated in both H and E and CK stained tumors (P = 0.003 and 0.001 respectively). Conclusion: This study supported the relevance of TB in the assessment of CRC aggressiveness. It also revealed that Lgr5 expression is related to morphologic features in the invasive front of CRC. Lgr5 could have an important role in forming a morphologic feature at the invasive front associated with the aggressiveness of the tumor.

Tumor Budding en cáncer rectal. Relación entre la densidad de los brotes tumorales y otros factores pronósticos / Budding tumor in rectal cancer. Relationship between tumor outbreak density and other prognostic factors

Introducción: El budding tumor (BT) es la presencia de células tumorales aisladas o en pequeños grupos situadas en el frente de invasión del tumor. Su hallazgo en alto grado es un factor de mal pronóstico independiente del cáncer colorrectal. El objetivo de este trabajo es determinar si el grado de BT está asociado con otros factores pronósticos del cáncer rectal. Material y métodos: Se incluyen las resecciones oncológicas de recto en el período 2013-2017. Los casos se agruparon según la densidad en la formación de los BT en 3 grupos, los de grado bajo, intermedio y alto. Se utilizó como valor estadístico el cálculo del odds ratio (OR). Resultados: Se analizaron las piezas de resección de 27 pacientes (15 mujeres y 12 hombres) con una media de edad de 68,4 años (40-86). Se calculó el OR para invasión ganglionar, vascular y recidiva en función del grado de budding tumoral. Discusión: Se observó una tendencia a la presencia de factores histológicos de mal pronóstico en relación al budding de alto grado, si bien el bajo número de casos no permitió demostrarlo en este estudio. Conclusiones: El análisis del grado de tumor budding es reproducible y podría ayudar a identificar pacientes con cáncer rectal de peor pronóstico. (AU)

Introduction: Tumor budding (BT) is defined as isolated or small groups of neoplastic cells located at the invasive front of the tumor. High-grade BT is a poor prognostic factor in colorectal cancer. Objective: To determine if the degree of BT is associated with other prognostic factors in rectal cancer. Materials and methods: Rectal oncological resections during the 2013-2017 period were included. Cases were stratified according to the density in the formation of BT in 3 groups: low, intermediate and high. The calculation of the odds ratio (OR) was used as a statistical value. Results: The resection specimens of 27 patients (15 women and 12 men) with a mean age of 68.4 years (40-86) were analyzed. OR for node metastases, vascular invasion and relapse was calculated according to tumor budding grade. Discussion: High-grade tumor budding seems to associate with the presence of poor prognostic factors. However, it was not possible to demonstrate it because of the small sample size. Conclusions: Tumor budding is a reproducible marker and could help to identify rectal cancer patients with a worse prognosis. (AU)

Growth pattern, tumor budding and CD8+T lymphocyte infiltration in colorectal adenocarcinoma invasive margins: association with clinicopathological features / 中国肿瘤临床

Objective: The aim of this study was to explore the correlation between the clinicopathological characteristics of colorectal adenocarcinoma and the growth pattern, tumor budding, and CD8+T lymphocyte infiltration in anterior invasive margins, and to assess their value as prognostic indicators. Methods: Paraffin embedded samples were collected from 126 patients with primary colorectal adenocarcinoma who underwent surgical resection in Zhangye People's Hospital Affiliated to Hexi College from January 2008 to December 2019. A total of 126 pathological sections were stained by immunohistochemistry. Anti-cytokeratin antibodies were used to mark tumor cell budding and anti-CD8 antibody markers T lymphocytes were evaluated. Results: In colorectal adenocarcinoma, infiltrative growth patterns and high-grade tumor budding in invasive margins were significantly associated with pathological stage of tumor size (pT) (P=0.029 and P<0.001, respectively), pathological stage of lymph node metastasis (pN) (P<0.001 and P=0.023, respectively) and vessel infiltration (P<0.001 and P<0.001, respectively). Furthermore, high-grade CD8+T lymphocyte infiltration was associated with the absence of lymph node metastases (P=0.050). Conclusions: Infiltrative growth patterns and high-grade tumor budding in colorectal adenocarcinoma invasive margins were correlated with patient prognosis. Importantly, these two features are easily detectable (with the help of pan-cytokeratin immunohistochemistry staining), in a reproducible manner. Therefore, we propose that they could be used as prognostic indicators in colorectal adenocarcinoma patients.