Tumor Budding Research Articles

Establish a novel tumor budding-related signature to predict prognosis and guide clinical therapy in colorectal cancer

Tumor budding is a long-established independent adverse prognostic marker for colorectal cancer (CRC), yet assessment of tumor budding was not reproducible. Therefore, development of precise diagnostic approaches to tumor budding is in demand. In this study, we first performed bioinformatic analysis in our single-center CRC patients’ cohort (n = 84) and identified tumor budding-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify hub genes and construct a prognostic signature. Nomogram model was used to identified hub genes score for tumor budding, and the receiver operating characteristic (ROC) curve and calibration plot indicated high accuracy and stability of hub gene score for predicted the prognosis of CRC. The association between budding-associated hub genes and score and prognosis of CRC were further verified in TCGA CRC cohort (n = 342). Then gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore the signaling pathways related to the tumor budding and validated by immunohistochemistry (IHC) of our clinical samples. Subsequently, immune infiltration analysis demonstrated that there was a high correlation between hub genes score and M2-like macrophages infiltrated in tumor tissue. In addition, somatic mutation and chemotherapeutic response prediction were analyzed based on the risk signature. In summary, we established a tumor budding diagnostic molecular model, which can improve tumor budding assessment and provides a promising novel molecular marker for immunotherapy and prognosis of CRC.

Clinicopathological features of colon cancer depending on the dMMR status of the tumor

Aim. To conduct a clinical and morphological assessment of the characteristics of colon cancer depending on the dMMR / pMMR status of the tumor.Materials and methods. A retrospective study included 66 patients with operable colorectal cancer (CRC) (T1-4bN0-2bM1), who were treated at Cancer Research Institute of Tomsk National Research Medical Center (NRMC). The average age of the patients was 64.4 ± 12.8 years. All patients underwent hemicolectomy or colon resection, as well as intraoperative resection of distant metastases, if present.Results. We determined that in CRC patients with pMMR tumors, hematogenous metastases were detected in 27.3% of cases, while in patients with dMMR tumors, hematogenous metastases were detected only in 6.1% of cases (p = 0.021). A comparative analysis of dMMR and pMMR tumors also allowed to establish higher frequency of perineural invasion among the pMMR subgroup of carcinomas (p = 0.039). The sign of tumor budding was found both in dMMR carcinomas (36%) and in pMMR tumors (45%). This sign was associated with damage to regional lymph nodes (p = 0.0017). A more detailed analysis of the tumor budding phenomenon showed that in dMMR tumors, Bd1 low-grade budding (83%) predominated. In pMMR tumors, Bd2 intermediate-grade budding (33%) and Bd3 high-grade budding (26.7%) prevailed. Bd2 and Bd3 tumor budding types were associated with hematogenous metastasis (p < 0.001).Conclusion. The obtained data demonstrate the differences in such pathomorphological parameters as perineural invasion and the degree of tumor budding depending on the dMMR / pMMR status of the tumor. These histologic parameters in tumor tissue are also associated with higher incidence of distant metastasis in patients with pMMR carcinomas as opposed to patients with dMMR tumors.

The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implications.

Colorectal cancer (CRC) is a leading cause of death worldwide. Despite the advances in surgical and therapeutic management, tumor metastases and poor prognosis are still major problems. Tumor budding is a relevant prognostic factor in CRC, and it can predict tumor metastasis. Galectin3 is responsible for the development and progression of many cancers through the regulation of cell-cell/cell-matrix interactions and tumor cell invasion. Tubulin is a microtubule protein, and maspin is a serine protease inhibitor; both induce tumor cell invasion through the stimulation of epithelial-mesenchymal transition. This study aims to evaluate the relationship between the expression of galecin3, tubulinβ, and maspin in CRC and clinicopathological features, including tumor budding, their prognostic roles, and clinical implications using immunohistochemistry. Galectin3, tubulinβ, and maspin were detected in tumor cells in 95%, 65%, and 87.5% of cases and in stromal cells in 28.8%, 40%, and 0% of cases. High expression of galectin3 and tubulinβ expression either in tumor cells or stroma was significantly associated with aggressive tumor features such as lymph node metastasis, lymphovascular invasion, tumor budding, and advanced tumor stage. The nucleocytoplasmic expression of maspin in tumor cells showed a significant association with deeper tumor invasion, lymph node metastasis, tumor budding, and advanced tumor stage. Significant associations were found between high galectin3 tumor cell expression and nucleocytoplasmic maspin and shorter survival. High expression of galectin3, tubulinβ, and nucleocytoplasmic maspin were significantly associated with aggressive tumor features such as tumor invasion, metastasis, high tumor budding, and short survival in CRC. They could be used as biomarkers for tumor budding and tumor aggressiveness in CRC and may be considered for future target therapy.

Unraveling a Histopathological Needle-in-Haystack Problem: Exploring the Challenges of Detecting Tumor Budding in Colorectal Carcinoma Histology

Background: In this study focusing on colorectal carcinoma (CRC), we address the imperative task of predicting post-surgery treatment needs by identifying crucial tumor features within whole slide images of solid tumors, analogous to locating a needle in a histological haystack. We evaluate two approaches to address this challenge using a small CRC dataset. Methods: First, we explore a conventional tile-level training approach, testing various data augmentation methods to mitigate the memorization effect in a noisy label setting. Second, we examine a multi-instance learning (MIL) approach at the case level, adapting data augmentation techniques to prevent over-fitting in the limited data set context. Results: The tile-level approach proves ineffective due to the limited number of informative image tiles per case. Conversely, the MIL approach demonstrates success for the small dataset when coupled with post-feature vector creation data augmentation techniques. In this setting, the MIL model accurately predicts nodal status corresponding to expert-based budding scores for these cases. Conclusions: This study incorporates data augmentation techniques into a MIL approach, highlighting the effectiveness of the MIL method in detecting predictive factors such as tumor budding, despite the constraints of a limited dataset size.

Association of circulating tumor DNA (ctDNA) molecular disease (MRD) detection with lymph node metastasis after local excision of pathological T1 colorectal cancer: First results from DENEB, a CIRCULATE-Japan GALAXY substudy.

23 Background: Patients with pathological T1 (pT1) colorectal cancer (CRC) at high risk for lymph node metastasis (LNM) after complete local resection are recommended to receive additional intestinal resection along with lymph node dissection. However, the existing pathological criteria for risk stratification of LNM are inadequate, such that ~90% of patients without LNM are exposed to potentially unnecessary treatment. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective substudy within the GALAXY observational study, to explore the ability of predicting LNM using circulating tumor DNA (ctDNA) detection compared to the standard pathological criteria. Methods: This study included patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk-stratification criteria for LNM. The additional surgery was indicated for patients meeting any of the following criteria: (1) depth of submucosal invasion (>1000µm); (2) lymphovascular invasion; (3) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma; and (4) high-grade tumor budding (BD2/3) at the site of deepest invasion according to the Japanese guideline. ctDNA was analyzed from plasma samples collected within 4 weeks before the additional intestinal resection using a personalized, tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay). The study assessed the diagnostic concordance rate between ctDNA detection and the occurrence of LNM. Results: Of 208 CRC patients enrolled between July 2021 and May 2023 in DENEB, 166 patients met the inclusion criteria. Of these, 22 (13.3%) were ultimately diagnosed with pStage III due to the presence of LNM in additional intestinal resection. Among the 166 patients, 6 patients tested ctDNA-positive; all 6 had LNM, yielding a positive predictive value of 100.0%. On the other hand, 160 patients had ctDNA-negative results, 144 of whom did not have LNM, resulting in a negative predictive value of 90.0%. The overall diagnostic concordance rate for ctDNA in detecting LNM was 90.4% (95% confidence interval, 84.8% to 94.4%). All 6 patients with a ctDNA-positive result and LNM had left-sided colorectal cancer and a tumor diameter greater than 13 mm. Conclusions: This analysis showed that ctDNA testing has the potential to improve risk stratification of LNM in patients with pT1 CRC who underwent complete local resection. Clinical trial information: UMIN000039205 .

Long-term outcomes of endoscopic or surgical resection in T1 colorectal cancer patients: a retrospective cohort study.

The personalized treatments of T1 colorectal cancer (CRC) remains controversial. We compared the long-term outcomes of T1 CRC patients after endoscopic resection (ER) and surgery, and evaluated the risk factors for the long-term prognosis. T1 CRCs after resection at the Cancer Hospital, Chines Academy of Medical Sciences from June 2011 to November 2021 were reviewed. High-risk factors included positive resection margin, poor differentiation, deep submucosal invasion (DSI ≥ 1000 μm), lymphovascular invasion and intermediate/high tumor budding. Comparative analyses were conducted based on three treatment methods: follow-up after ER (Group A), additional surgery after ER (Group B) and initial surgery (Group C). The primary endpoints included recurrence-free survival (RFS) and overall survival (OS). Cox proportional hazard regression models were constructed to identify risk factors for RFS and OS. A total of 528 patients were enrolled (173 patients in Group A, 102 patients in Group B, 253 patients in Group C). The 3-year RFS, 5-year RFS, 3-year OS, and 5-year OS rates were 96.7%, 94.7%, 99.1%, and 97.8%, respectively. In the absence of other high-risk factors, RFS (P = 0.321) and OS (P = 0.155) of patients with DSI after ER were not inferior to those after surgery. Multivariate analyses identified sex (HR 0.379; 95% CI 0.160-0.894), Charlson comorbidities index (CCI) (HR 3.330; 95% CI 1.571-7.062), margin (HR 8.212; 95% CI 2.325-29.006), and budding (HR 3.794; 95% CI 1.686-8.541) as independent predictive factors of RFS, and identified CCI (HR 10.266; 95% CI 2.856-36.899) as an independent predictive factor of OS. The long-term outcomes of ER are comparable to those of surgery in T1 CRC patients with DSI when other high-risk factors are negative. Resection margin, tumor budding, sex, and CCI may be the most important long-term prognostic factors for T1 CRC patients.

Comparison between Peritumoral and Intratumoral Budding in Colorectal Cancer.

Tumor budding (TB) is classified, based on location, into peritumoral budding (PTB) or intratumoral budding (ITB). This study aimed to evaluate the relationship between PTB and ITB in colorectal cancers (CRCs). PTB and ITB were investigated and subsequently divided into high and low groups. CRCs were divided into three groups: (1) high PTB/ITB, (2) high PTB or ITB, and (3) low PTB/ITB. The clinicopathological and prognostic significances were evaluated according to the three tumor budding (TB) groups. High PTB/ITB and low PTB/ITB were identified in 32 (12.0%) and 135 (50.8%) patients, respectively. A total of 99 patients (37.2%) were found to have high PTB or ITB. TB was significantly correlated with lymphatic and perineural invasion, lymph node metastasis, metastatic lymph node ratio, distant metastasis, and a higher pTNM stage. A significant correlation was found between high PTB and high ITB (p = 0.010). The amount of PTB was found to increase significantly with the amount of ITB (p < 0.001) in a linear regression test. Patients with high PTB/ITB had worse overall and recurrence-free survival than those with high PTB or ITB. Conversely, patients with low PTB/ITB had better overall and recurrence-free survival rates than those with high PTB or ITB. However, there was no significant difference in overall and recurrence-free survival between patients with high PTB/low ITB and high ITB/low PTB (p = 0.336 and p = 0.623, respectively). In summary, the presence of TB, regardless of PTB or ITB, was significantly correlated with aggressive tumor behavior and a worse prognosis than the absence of TB. Additionally, the present study demonstrated that it is feasible to stratify the prognosis of patients based on whether they have both PTB and ITB or only one of the two.

To study the utility of tumor budding as a histopathological marker in comparison to various histopathological parameters and TNM staging in breast carcinoma

Background Breast cancer is the leading cause of death in Indian females. Detection of breast cancer in later stages leads to poorer prognosis and therefore decreases patient survival. Various new modalities such as mammography and USG guided FNACs are developed and many new markers are available to diagnose breast cancer; however, tumour budding is a cost-effective method which can be helpful in early diagnosis. Tumour buds are found to have a positive correlation with various histopathological prognostic markers in breast cancer. The present study will be conducted to evaluate tumour buds as a prognostic marker in breast cancer. This study aims to compare tumour budding with histopathological prognostic markers, TNM staging and IHC phenotypes. Methods The study will be observational, cross- sectional, and prospective, will include 60 cases and will be conducted at Jawaharlal Nehru Medical College (JNMC) Wardha in the Pathology Department. Results Data will be collected and combined together over a period of two years and will be analysed statistically for tumour budding as a marker and its correlation with breast prognosis.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer.

Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Molecular subtyping of head and neck cancer – Clinical applicability and correlations with morphological characteristics

AimWe aimed to evaluate the applicability of a customized NanoString panel for molecular subtyping of recurrent or metastatic head and neck squamous cell carcinoma (R/M−HNSCC). Additionally, histological analyses were conducted, correlated with the molecular subtypes and tested for their prognostic value. Material and MethodsWe conducted molecular subtyping of R/M−HNSCC according to the molecular subtypes defined by Keck et al. For molecular analyses a 231 gene customized NanoString panel (the most accurately subtype defining genes, based on previous analyses) was applied to tumor samples from R/M−HNSCC patients that were treated in the CeFCiD trial (AIO/IAG-KHT trial 1108). A total of 130 samples from 95 patients were available for sequencing, of which 80 samples from 67 patients passed quality controls and were included in histological analyses. H&E stained slides were evaluated regarding distinct morphological patterns (e.g. tumor budding, nuclear size, stroma content). ResultsDetermination of molecular subtypes led to classification of tumor samples as basal (n = 46, 45 %), inflamed/mesenchymal (n = 31, 30 %) and classical (n = 26, 25 %). Expression levels of Amphiregulin (AREG) were significantly higher for the basal and classical subtypes compared to the mesenchymal subtype. While molecular subtypes did not have an impact on survival, high levels of tumor budding were associated with poor outcomes. No correlation was found between molecular subtypes and histological characteristics. ConclusionsUtilizing the 231-gene NanoString panel we were able to determine the molecular subtype of R/M−HNSCC samples by the use of FFPE material. The value to stratify for different treatment options remains to be explored in the future. The prognostic value of tumor budding was underscored in this clinically well annotated cohort.

Machine Learning and Radiomics Analysis for Tumor Budding Prediction in Colorectal Liver Metastases Magnetic Resonance Imaging Assessment.

We aimed to assess the efficacy of machine learning and radiomics analysis using magnetic resonance imaging (MRI) with a hepatospecific contrast agent, in a pre-surgical setting, to predict tumor budding in liver metastases. Patients with MRI in a pre-surgical setting were retrospectively enrolled. Manual segmentation was made by means 3D Slicer image computing, and 851 radiomics features were extracted as median values using the PyRadiomics Python package. Balancing was performed and inter- and intraclass correlation coefficients were calculated to assess the between observer and within observer reproducibility of all radiomics extracted features. A Wilcoxon-Mann-Whitney nonparametric test and receiver operating characteristics (ROC) analysis were carried out. Balancing and feature selection procedures were performed. Linear and non-logistic regression models (LRM and NLRM) and different machine learning-based classifiers including decision tree (DT), k-nearest neighbor (KNN) and support vector machine (SVM) were considered. The internal training set included 49 patients and 119 liver metastases. The validation cohort consisted of a total of 28 single lesion patients. The best single predictor to classify tumor budding was original_glcm_Idn obtained in the T1-W VIBE sequence arterial phase with an accuracy of 84%; wavelet_LLH_firstorder_10Percentile was obtained in the T1-W VIBE sequence portal phase with an accuracy of 92%; wavelet_HHL_glcm_MaximumProbability was obtained in the T1-W VIBE sequence hepatobiliary excretion phase with an accuracy of 88%; and wavelet_LLH_glcm_Imc1 was obtained in T2-W SPACE sequences with an accuracy of 88%. Considering the linear regression analysis, a statistically significant increase in accuracy to 96% was obtained using a linear weighted combination of 13 radiomic features extracted from the T1-W VIBE sequence arterial phase. Moreover, the best classifier was a KNN trained with the 13 radiomic features extracted from the arterial phase of the T1-W VIBE sequence, obtaining an accuracy of 95% and an AUC of 0.96. The validation set reached an accuracy of 94%, a sensitivity of 86% and a specificity of 95%. Machine learning and radiomics analysis are promising tools in predicting tumor budding. Considering the linear regression analysis, there was a statistically significant increase in accuracy to 96% using a weighted linear combination of 13 radiomics features extracted from the arterial phase compared to a single radiomics feature.

Effects of tumour budding on adjuvant chemotherapy in colorectal cancer.

High tumour budding has been indicated as a risk factor of poor survival in colorectal cancer. This study aimed to investigate the impact of tumour budding grades and the use of adjuvant chemotherapy on prognosis in patients with colorectal cancer. This study included consecutive colorectal cancer patients who underwent radical surgery for primary colorectal adenocarcinoma at The Sixth Hospital of Sun Yat-sen University between 2009 and 2019. Tumour budding was assessed based on the recommendations of the International Tumor Budding Consensus Conference using haematoxylin and eosin (H&E)-stained slides with tumour samples. The primary outcome of interest was to correlate tumour budding with disease-free survival and overall survival; the secondary outcome was investigation of the impact of adjuvant therapy on different tumour budding grades. In addition, a subgroup analysis was performed for the effects of lymphocytic infiltration on adjuvant chemotherapy in patients with Bd3. Of 709 eligible patients, 412 with colorectal cancer were included. According to the International Tumor Budding Consensus Conference, 210 (50.9 per cent), 127 (30.8 per cent) and 75 (18.2 per cent) were classified as low budding (Bd1), intermediate budding (Bd2) and high budding (Bd3) respectively. Patients with Bd1, Bd2 and Bd3 had 5-year disease-free survival rates of 82.9 per cent, 70.1 per cent and 49.3 per cent respectively, and 5-year overall survival rates of 90 per cent, 79.5 per cent and 62.7 per cent respectively (P <0.001). Adjuvant chemotherapy yielded a significant survival benefit in patients with Bd3 (5-year disease-free survival, 65 per cent versus 31.4 per cent, P <0.001; 5-year overall survival, 84.4 per cent versus 63.1 per cent, P <0.001), but not in those with Bd1 or Bd2. In patients with Bd3, the benefit of adjuvant chemotherapy was maintained in those with low, but not high lymphocytic infiltration. High grade of tumour budding was strongly correlated with poorer survival outcomes in colorectal cancer. Patients with Bd3 benefited from adjuvant chemotherapy, with the exclusion of patients with high lymphocytic infiltration.

High KRT17 expression in tumour budding indicates immunologically 'hot' tumour budding and predicts good survival in patients with colorectal cancer.

Emerging evidence has demonstrated that tumour budding (TB) is negatively associated with T-lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically 'hot' TB remain poorly understood. We quantified the number of TB by haematoxylin-eosin (H&E) sections and the densities of CD3+ and CD8+ T-lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T-lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB-positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed. In a CRC cohort of 351 cases, low-grade TB was associated with high CD3+ and CD8+ T-cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparentassociation with TB-grade and T-lymphocyte infiltration. In 278 TB-positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low-grade TB and positively associated with high CD3+ and CD8+ T-cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease-free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T-lymphocyte infiltration. KRT17 can be employed as a new indicator for distinguishing different immunological TBs.

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

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. 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. 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. 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.

Relevance of Tumor Budding and Pattern of Invasion in Oral Squamous Cell Carcinoma.

Standard histopathological parameters such as depth of invasion (DOI), lymphovascular invasion (LVI), and perineural invasion (PNI) are known parameters that can correlate with the prognosis and aggressiveness of oral squamous cell carcinomas (OSCCs). Tumor budding (TB) (≤5 tumor cells at infiltrating borders) and pattern of invasion (POI) are emerging histopathological parameters that have shown promising results as reliable risk factors in predicting nodal metastasis in early OSCCs. The aim of the study was to assess TB and POI in OSCCs. A total of 33 surgical resection specimens of OSCC, including buccal mucosa and tongue with neck dissection, were selected. TB and POI along with standard parameters such as grade, DOI, LVI, PNI, lymph node status, and pathological staging were evaluated. These parameters were analyzed in comparison with lymph node involvement and pathological stage of the tumor using the Chi-square and Fischer's exact test. The SPSS software, v21, was used for statistical analyses. Most of OSCC were moderately differentiated tumors (63.64%). TB was present in 23 cases, in which 69.57% of cases showed low TB (<5 buds), while 30.43% of cases had higher TB (>5 buds). The worst POI (Patterns 4 and 5) was seen in 75.76% of cases. TB, POI, grade, PNI, DOI, and stromal pattern were significantly associated with the pathological stage of the tumor. TB and POI are important and reliable in histopathological parameters in OSCCs.

Tumour budding in invasive breast carcinoma of no special type - relationship with clinicopathological parameters.

Each breast cancer is a heterogeneous tumour with different clinicopathological feature, and thus they all have different prognoses. Tumour budding (TB), considered as the first step in tumour metastasis, is the most critical factor for poor prognosis and is associated with the epithelial-mesenchymal transition (EMT). Tumour budding and its clinicopathological features in invasive breast carcinoma of no special type (NST). Patients who underwent surgery for invasive breast carcinoma (NST) between January 2018 and 2022 were retrospectively reviewed from the database, haematoxylin and eosin-stained slides were retrieved and reevaluated. The study included 200 patients. The mean number of TB was 12.8 ±9.6. The number of TB was significantly lower in patients who underwent neoadjuvant chemotherapy treatment ( p = 0.002). There was a weak positive correlation between TB count and tumour size ( r = 0.177). Triple-negative patients had significantly lower TB counts ( p = 0.001). No significant difference was observed between histological grade, nuclear grade, presence of ductal carcinoma in situ , stromal tumour-infiltrating lymphocytes, perineural invasion, lymph node metastasis, and number of TB ( p > 0.05). The number of TB was higher in oestrogen receptor positive tumours ( p = 0.015). There were more TB in patients with angiolymphatic invasion, which supports the pathophysiological relationship between tumour budding, metastasis, and EMT. Clarification of the mechanism of TB with more studies is promising in terms of treatment options.

Histopathologic and Prognostic Significance of Tumor Budding in Colorectal Adenocarcinoma: A Retrospective Cohort Study Conducted in Shiraz, Iran.

Colorectal cancer is the second reason for cancer-associated death. The prognosis of the malignancy is defined by TNM scoring. However, tumor grading, lymphovascular invasion, perineural invasion, and tumor buddings may affect its prognosis. This study aimed to assess the prognostic and histologic impact of tumor budding in colorectal adenocarcinoma. This study is a retrospective cohort of 192 patients with colorectal adenocarcinoma. All four stages of colorectal adenocarcinoma patients were included, but the patients in stages I and II were also analyzed separately. We used pathology reports to extract the histopathologic data. The prognostic values were extracted by calling the patients. Less than half of the patients were in stages I and II of the disease. According to our analysis, tumor extension and lymphovascular invasion were correlated with tumor budding count in patients in stages I and II, and lymphovascular invasion, tumor grade, tumor stage, lymph node involvement, tumor extension, tumor site, metastasis, and five-year survival were correlated with tumor budding within all stages. It is recommended that tumor budding count should be assessed and reported in pathology reports of adenocarcinomas due to its high correlation with poor prognosis.

Histologic, immunohistochemical, and in situ hybridization study of myxoid stroma in feline oral squamous cell carcinoma.

Oral squamous cell carcinoma (oSCC) is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma (SCC) remains unclear. This study aimed to reveal the cancer microenvironment of feline oSCC and evaluate the pathological mechanisms of progression. We used 19 samples from 17 cats with oSCC, which were examined using light microscopy, immunohistochemistry, and in situ hybridization (RNAscope®). Feline oSCCs had two types of stroma, namely fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin-eosin staining. The myxoid stroma was rich in hyaluronic acid, which seems to be produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer-associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oSCC and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer-associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for analyzing feline oSCC.

Tumour budding in gallbladder carcinoma.

Tumour budding in gallbladder carcinoma.

The Relationship Between Tumor Budding and Patient's Survival in Breast Cancer.

Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio.