Tumor Budding Research Articles

Serous Ovarian Carcinoma: Detailed Analysis of Clinico-Pathological Characteristics as Prognostic Factors

Background/Objectives: Serous ovarian carcinoma (SOC) is the most common subtype of epithelial ovarian cancer, with high-grade (HGSOC) and low-grade (LGSOC) subtypes presenting distinct clinical behaviours. This study aimed to evaluate histopathologic features in SOC, correlating these with prognostic outcomes, and explore the potential clinical implications. Methods: We analysed 51 SOC cases for lymphovascular space invasion (LVSI), tumour border configuration (TBC), microvessel density (MVD), tumour budding (TB), the tumour–stroma ratio (TSR), the stromal type, tumour-infiltrating lymphocytes (TILs), and tertiary lymphoid structures (TLSs). A validation cohort of 54 SOC cases from The Cancer Genome Atlas (TCGA) was used for comparison. Results: In the discovery set, significant predictors of aggressive behaviour included LVSI, high MVD, high TB, and low TILs. These findings were validated in the validation set where the absence of TLSs, lower peritumoural TILs, immature stromal type, and low TSR were associated with worse survival outcomes. The stromal type was identified as an independent prognostic predictor in SOC across both datasets. Inter-observer variability analysis demonstrated substantial to almost perfect agreement for these features, ensuring the reproducibility of the findings. Conclusions: The histopathological evaluation of immune and stromal features, such as TILs, TLSs, TB, TSR, and stromal type, provides critical prognostic information for SOC. Incorporating these markers into routine pathological assessments could enhance risk stratification and guide treatment, offering practical utility, particularly in low-resource settings when molecular testing is not feasible.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

Is Immunohistochemical Galectin-3 Expression Associated with the Epithelial-Mesenchymal Transition in High- and Low-Grade Invasive Urothelial Carcinomas of the Bladder?

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial-mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer: Does Submucosal Invasion Depth Really Matter?

After endoscopic resection of colorectal cancer with submucosal invasion (pT1 CRC), additional surgical treatment is recommended if deep submucosal invasion (DSI) is present. This study aimed to further elucidate the risk factors for lymph node metastasis (LNM) in patients with pT1 CRC, especially the effect of DSI on LNM. Patients with pT1 CRC who underwent lymph node dissection were selected. The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM. The submucosal invasion depth (SID) was measured via 4 methods and analyzed with 3 cut-off values. Twenty-eight of the 239 patients presented with LNM (11.7%), and the independent risk factors for LNM included high histological grade (P=0.003), lymphovascular invasion (LVI) (P=0.004), intermediate to high budding (Bd 2/3) (P=0.008), and cancer gland rupture (CGR) (P=0.008). Moreover, the SID, width of submucosal invasion (WSI), and area of submucosal invasion (ASI) were not significantly different. When one, two, three or more risk factors were identified, the LNM rates were 1.1% (1/95), 12.5% (7/56), and 48.8% (20/41), respectively. Indicators such as the SID, WSI, and ASI are not risk factors for LNM and are subjective in their measurement, which renders them relatively inconvenient to apply in clinical practice. In contrast, histological grade, LVI, tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant. It would be prudent to focus on these histological factors rather than subjective measurements.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Tumor budding in pre-neoadjuvant biopsy and post-neoadjuvant resection specimens is associated with poor prognosis in intrahepatic cholangiocarcinoma-a cohort study of 147 cases by modified ITBCC criteria.

Tumor budding (TB) has been associated with poor survival in a variety of cancers including intrahepatic cholangiocarcinoma (iCCA). As tumor histomorphological features are significantly altered after neoadjuvant therapy (NAT), our study aims to assess the prognostic significance of TB in iCCA patients before and after NAT, by the modified International Tumor Budding Consensus Conference (ITBCC) criteria. 147 NAT-treated iCCA cases were included in this study. In biopsy specimens obtained before NAT, the TB-positive subgroup had lower overall survival (OS) in univariate analysis (P = 0.010). In resection specimens obtained after NAT, the TB-positive subgroup had reduced OS (P = 0.002) and recurrence-free survival (RFS) (P = 0.013) in univariate analysis. In multivariate analysis including TNM stage, lymphovascular invasion and perineural invasion, TB-positive in post-NAT resection was also found as an independent prognostic factor for both OS and RFS (OS, HR, 3.005; 95% CI, 1.333-6.775, P = 0.008; RFS, HR, 1.748; 95% CI, 1.085-2.816, P = 0.022). In conclusion, assessing the presence of TB by modified ITBCC criteria provides robust prognostic information in the NAT setting of iCCA patients and can be considered to be included in routine pathological reporting.

Treatment strategy for cervical lymph node metastases from early-stage tongue and floor of the mouth squamous cell carcinoma using tumour budding and depth of invasion as predictors.

This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). Biopsy specimens of 103 patients diagnosed with early cT1-T2 cancer of the tongue and floor of the mouth were included. Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5mm and pDOI ≥ 5mm groups, and the positive and negative budding and depth of invasion (BD) score groups. In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. pDOI ≥ 5mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20mm.

Is Colonoscopy Alone Adequate for Surveillance in Stage I Colorectal Cancer?

While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to NCCN guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies. A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and CT scans. Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectal). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative CEA levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon cancer and 14.9% in rectal cancer). Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Correlation Between Tumor Budding and Survivin Expression in Colorectal Cancer.

Correlation of Survivin expression levels in tumor tissues and degree of tumor outgrowth with colorectal cancer characteristics. The pathological tissues of 90 cases of colorectal cancer were observed by HE staining, and the tumor budding was judged by Ueno standard, and the expression of Survivin was detected by immunohistochemistry (IHC) technique (EnVision method), so as to analyze the correlation between tumor budding, the expression level of Survivin and the degree of tumor budding, and the correlation between the tumor budding and the patients' clinical characteristics. The expression level of Survivin was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer; tumor outgrowth was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer (P < 0.05); the expression level of Survivin was significantly correlated with the degree of tumor budding in patients with colorectal cancer (P < 0.05). In this paper, we tested the relationship between Survivin and tumor budding in colon cancer, and analyzed its relationship with clinicopathological features, with a view to providing a reference for the mechanism related to colorectal cancer.

The Correlation of PD-L1 Overexpression With Tumor Budding In Cervical Carcinoma

Background: Several studies have proven the relationship between PD-L1, which is known as an immunotherapy target, and poor prognosis. The presence of a tumor budding (TB) group tumor outside the main tumor is also associated with a poor prognosis. The purpose of this study was to determine the relationship between PD-L1 and the grade of TB in cervical carcinoma. Methods: The design of this research is a case-control study with a retrospective approach. The sample is from a paraffin block of the primary cervical cancer tumor from the results of surgery in Balimed Denpasar Hospital between 2020 and 2023. From the statistical formula for the case-control study, a minimum sample of 15 is obtained for the case group with the criteria of high-grade TB, while 15 people were in the control group with low-grade TB. Immunohistochemistry (IHC) PD-L1 is positive if the membrane or cytoplasm is brown, and is negative if there is no brown color on the membrane or cytoplasm. Inferential statistics were used to evaluate the relationship between PD-L1 overexpression and low- and high-grade TB in cervical carcinoma using a chi-square test. Results: The results of this research revealed (p = 0.273) that there was no correlation between PD-L1 expression and high- and low-grade TB. Overexpression of PD-L1 was associated with a 2.250-fold increased risk of high-grade TB (OR = 2.250 with a 95% confidence interval of 0.103–1.915). Conclusions: The severity of TB does not correlate with PD-L1 expression. The functions of PD-L1 and other variables in the carcinogenesis of TB development are the cause of this weak association.

Predicting lymph node metastasis in gastric adenocarcinoma: Role of tumor budding and immunohistochemical expression of E-cadherin

Predicting lymph node metastasis in gastric adenocarcinoma: Role of tumor budding and immunohistochemical expression of E-cadherin

Sidedness and Molecular Pattern in Defining the Risk of Lymph Node Metastasis in Nonmetastatic Colorectal Cancer: Single-Center Retrospective Study.

Background: Lymphadenectomy plays a central role in the treatment of localized colon cancer. While in left colon cancer the D3 lymphadenectomy/CME is considered the standard of care, lymphatic stations to be removed in right colon cancer are still a matter of discussion. The individuation of LNM risk factors could help in choosing the lymphadenectomy in right-sided tumors. This study aims to analyze the correlation of histopathological and molecular characteristics with lymph node metastasis, both in right- and left-sided colon cancer, and their impact on survival; Methods: We conducted a single-center observational retrospective study. The following data were collected and analyzed for each patient: demographics, histopathological and molecular data, and intraoperative and perioperative data. Statistical analyses were performed, including descriptive statistics, multivariate logistic regression and survival analysis; Results: An association between tumor size (pT, p < 0.001), grading (p = 0.013), budding (p < 0.001), LVI (79,4% p < 0.001) and LNM was observed. A multivariate analysis identified pT4 (OR 5.45, p < 0.001) and LVI+ (OR 10.7, p < 0.001) as significant predictors of LNM. Right-sided patients presented a worse OS when associated with LNM, while no significant difference was observed in N0 patients; Conclusions: histological and molecular analysis can help identify high risk patients, which could benefit from extended lymphadenectomies. These patients could be ideal candidates for the D3 lymphadenectomy/CME.

Tumour Budding in Oral Squamous Cell Carcinoma: A Narrative Review.

Tumour budding is an emerging prognostic factor in oral squamous cell carcinoma (OSCC) that reflects the invasive behaviour of the tumour. This narrative review aims to provide a comprehensive overview of the role of tumour budding in OSCC, synthesizing current research and clinical findings. We explore the definition and characterization of tumour budding, its correlation with histopathological features, and its impact on patient outcomes. Tumour budding is associated with increased local invasion, lymph node metastasis, and poor overall survival, highlighting its potential as a key marker for aggressive disease. This review also discusses the methods used to assess tumour budding, including histological scoring systems and the challenges in standardizing these assessments. By integrating findings from recent studies, we offer insights into the clinical relevance of tumour budding in OSCC management and propose future research directions to enhance its application in personalized treatment strategies.

The relationship between tumor budding and survival of patients with breast cancer: A meta-analysis.

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.

Potential predictor of prognosis in breast carcinoma: Tumor budding

ABSTRACT Background: Breast cancer is the most common cancer in women, with invasive breast carcinoma of no special type (IBC-NST) accounting for the majority of cases. Aim: This study aimed to evaluate the relationship between tumor budding (TB), which is the earliest histological indicator of tumor spread and represents epithelial–mesenchymal transition, and prognostic factors as well as the effect of TB on survival in patients with IBC-NST, thereby demonstrating its potential prognostic value. Materials and Methods: This study included 278 cases of breast resection diagnosed with IBC-NST from 2014 to 2019. Total tumor buds were counted in 10 high-power fields of a hematoxylin and eosin–stained section with the most infiltrative area at 400× magnification. The cutoff value for TB was obtained using receiver operating characteristic analysis for mortality and recurrence risk; this cutoff value was used to classify TB into two categories: low and high grades. The relationship between TB and prognostic factors and the effect of TB on the survival of patients were investigated. Results: This study revealed a statistically significant relationship between high-grade TB and increased tumor size, advanced pathological primary tumor (pT) category, lymph node metastasis, lymphatic invasion, blood vessel invasion, increased recurrence, and mortality as well as reduced overall and disease-free survival. Conclusion: TB in breast carcinomas may have significant predictive value for prognosis. It emerges as a simple, reproducible, and cost-effective histological marker. With the standardization of evaluation criteria, TB may be readily integrated into routine pathological examination, thereby increasing its value in clinical patient management.

The prognostic significance of growth pattern, tumor budding, poorly differentiated clusters, desmoplastic reaction pattern and tumor-stroma ratio in colorectal cancer and an evaluation of their relationship with KRAS, NRAS, BRAF mutations

Growth pattern (GP), tumor budding (TB), poorly differentiated clusters (PDC), desmoplastic reaction pattern (DRP) and tumor-stroma ratio (TSR) are prognostic histomorphological parameters in colorectal cancer (CRC). Correlations between these parameters, their individual prognostic values, and their relationship with KRAS/NRAS/BRAF mutations have not been comprehensively examined. We aimed to investigate these associations, which have not been previously explored in this combination. 126 CRC cases were included. GP, TB, PDC, DRP and TSR were evaluated by two experienced pathologists. KRAS/NRAS/BRAF mutation profile were determined using qPCR. Demographic, clinicopathological and survival data were recorded. Interrelations were investigated by statistical analysis. Infiltrative GP was more frequent in high-score TB, PDC-G3, and stroma-high tumors (p < 0.05). High-score TB was more common in PDC-G3 and stroma-high tumors (p < 0.05). Immature DRP was more frequent in stroma-high tumors (p = 0.014). Among histomorphological parameters, a significant relationship was found only between infiltrative GP and the presence of KRAS mutation (p = 0.023). Moreover, GP was significantly associated with pT, lymphatic invasion, perineural invasion (p < 0.05). Effects on survival were assessed using Kaplan-Meier method and Cox proportional hazards model. TB and PDC were identified as independent predictors of overall survival. Higher TB score (p = 0.008) and higher PDC grade (p = 0.013) lead to worse survival. Interestingly, GP, DRP, TSR or KRAS/NRAS/BRAF mutations were not associated with overall survival. Our results highlight the prognostic significance of TB and PDC. We suggest incorporating TB and PDC into routine CRC reports. The association of KRAS mutation with infiltrative GP supports its role in the acquisition of invasive behavior.

Local Invasion Patterns Characterized by SARIFA and Tumor Budding Differ and Have Distinct Prognostic Significance in Esophageal Adenocarcinoma and Squamous Cell Carcinoma.

Both esophageal squamous cell carcinoma (ESQCC) and adenocarcinoma (EAC) are known to have poor prognosis. We aimed to investigate the invasion front areas of 57 ESQCC and 43 EAC cases to find histological signs of metastatic progression. Tumor cell clusters with different cell counts, including tumor buds (TBs) and poorly differentiated clusters (PDCs), were assessed. The presence of the recently described Stroma AReactive Invasion Front Area (SARIFA) phenomenon, which defines a direct contact between tumor cells and adipocytes, was more frequently observed in EAC than in ESQCC (p = 0.004). In adenocarcinomas, a higher prevalence of SARIFA was observed in tumors with a higher number of small clusters (TBs and small PDCs; p < 0.001); furthermore, both the high number of TBs (p = 0.016) and the presence of SARIFA (p = 0.001) correlated with a higher pT stage. SARIFA positivity in EAC (p = 0.011) and high TB in ESQCC (p = 0.0006) were found to be independent prognostic factors for lymph node metastases. Moreover, in ESQCC, the higher absolute number of both TBs and PDCs was associated with shorter overall survival (p = 0.0269 and p = 0.0377, respectively). Our results suggest that the histological subtypes of esophageal cancer behave differently, namely, that different features of the invasion front are of prognostic significance.

Exploring the Usefulness of Tumor Budding as a Histopathological Marker Compared to Tumor-Node-Metastasis (TNM) Staging in Breast Cancer.

Tumor budding, defined as small clusters of tumor cells at the invasive front of carcinomas, has gained attention as a potential prognostic marker in various cancers. This study aimed to evaluate the utility of tumor budding as a histopathological marker in breast cancer and compare it to traditional prognostic markers such as histological grading, tumor-node-metastasis (TNM) staging, and molecular subtypes. A prospective, cross-sectional study was conducted over two years (June 2022 to May 2024) in the Department of Pathology at Jawaharlal Nehru Medical College, Wardha. Seventy-two female patients diagnosed with breast carcinoma who underwent modified radical mastectomy were included. Tumor budding was assessed through histopathological analysis and categorized as high or low. Statistical correlations were established between tumor budding and tumor size, histological grade, lymph node involvement, vascular invasion, and molecular subtypes (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and triple-negative breast cancer, TNBC). The chi-square test and multiple regression analyses were applied to assess significance. High tumor budding was observed in 68.1% of patients and was significantly associated with larger tumor size (p = 0.040), higher histological grade (p = 0.009), lymph node metastasis (p = 0.002), and vascular invasion (p = 0.003). The postmenopausal age group (>55 years) demonstrated a higher prevalence of high budding (p = 0.010). No significant correlation was found between tumor budding and molecular subtypes (p = 0.39), although high budding was more frequent in TNBCcases. Tumor budding is significantly associated with more aggressive tumor characteristics in breast cancer. Incorporating tumor budding into routine pathological assessments alongside TNM staging and histological grading may enhance the ability to identify high-risk patients and guide treatment strategies. Further large-scale, multicenter studies are warranted to confirm its prognostic value.

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCCarising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant. Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.