Degree Of Budding Research Articles

Pathomorphological analysis of budding in colorectal carcinomas

Morbidity and mortality from colorectal cancer (CRC) remains a current problem of modern oncology. Intensive budding is an important prognostic factor for a worse clinical course of CRC and may influence clinical decision-making regarding the use of extended interventions in pT1 and stage II, according to the conclusion of the 2016 International Consensus Conference on Tumor Budding. The aim of the work is to evaluate the prognostic significance of budding depending on the clinical and morphological characteristics of colorectal carcinomas. Materials and methods. The article deals with clinical and anatomical material of 31 patients with CRC (14 women and 17 men) who were treated in the 2nd surgical department of the SE “Dnipropetrovsk Regional Clinical Hospital” in the period from 2019 to 2021. The age of the patients varied of 27–84 years old (average age – 62.3 ± 14.8 years old). A histological examination of CRC samples was carried out with an assessment of “hot areas” of the invasive front and an immunohistochemical examination with РАН CK АЕ 1/3, Ki-67, MUC2, caspase-3, β-catenin to calculate the number of tumor cell clusters. Results. In one third of the number of samples, differences were determined not only in the number of clusters, but also in the budding category when stained by routine and immunohistochemical methods. Peritumoral budding of the invasive front with category Bd3 was always accompanied by intratumoral budding of varying degrees of intensity. The analysis of the distribution of gradations of budding of colorectal carcinomas by gender, age, location, histological degree of differentiation, and the presence of metastases did not show a statistically significant difference (p > 0.05), which may indicate the independence of this factor on the prognosis of patient survival. The intensity of budding of colorectal carcinomas depending on the expression of markers Ki-67, caspase-3 and β-catenin did not show a significant difference in subgroups (p > 0.05) but showed tendencies to increase the number of budding with an increase in the proliferation index and a decrease in the activity of the proapoptotic enzyme caspase-3. Conclusions. If the number of buds on the border of categories Bd1 and Bd2, or Bd2 and Bd3, determined by the standardized method of H & E staining is doubtful, the degree of budding may be underestimated in comparison with staining by the immunohistochemical method, due to the exclusion of falsely interpreted morphological objects as tumor clusters; the most reliable immunohistochemical marker for contrast separation of buds is a cocktail of cytokeratins.

Gross morphologic appearance of chorionic villi and the risk of chromosomal abnormalities.

Chromosomal abnormalities are associated with changes in complex aspects of chorionic villi histomorphology. This study used a simple scoring system to evaluate the association between atypical gross morphology and abnormal chromosomal testing on chorionic villus sampling (CVS). This retrospective cohort study included singleton pregnancies that underwent CVS at a single institution from 2006-2017. The degree of budding, branching, and vascularity (BBV) was scored from 0 to 3 for each CVS specimen, and individual scores were summed to calculate a composite BBV score. Scores were categorized into typical or atypical based on the cohort's distribution. The primary predictor was atypical BBV score, and the primary outcome was chromosomal abnormality. Fisher's exact test compared proportions, and logistic regression generated odds ratios. Among 1171 CVS specimens, 28% had chromosomal abnormalities. The chromosomally abnormal group had a higher rate of atypical BBV score than the normal group (7.3% vs 3.7%, P=0.009), a finding that remained statistically significant after controlling for maternal age, gestational age, and mode of CVS (aOR 2.2, 95% CI 1.24-3.82). Atypical chorionic villus morphology is associated with chromosomal abnormalities. This scoring system is simple, rapid, and easy to perform at the time of routine diagnosis.

Wetting-Induced Budding of Vesicles in Contact with Several Aqueous Phases

Osmotic deflation of vesicles enclosing two liquid phases can lead to bulging of one of the phases from the vesicle body. This budding process is preceded by a complete to partial wetting transition of one of the liquid phases on the membrane and depends on the membrane tensions and the tension of the interface between the enclosed liquid phases. These tensions dominate in different morphology regimes, the crossover of which initiates the budding process. In addition, the degree of budding can be controlled by aspiration via micropipets. We also demonstrate that the budding direction can be reversed if there are two external phases in contact with the vesicle.

Tumour budding at invasive margins and outcome in colorectal cancer

Tumour budding, defined as small clusters of undifferentiated cancer cells at invasive margins, has been shown to reflect biologic aggressiveness of colorectal cancers. We therefore examined the prognostic significance of tumour budding in patients with colorectal carcinoma, particularly focusing on comparisons with other clinicopathological findings. Tumour budding was investigated in surgically resected specimens from 159 patients with colorectal carcinoma. With haematoxylin and eosin stained slides containing the entire invasive margin, the degree of tumour budding was classified into three grades: mild, <1/3 of the entire invasive margin; moderate, 1/3-2/3; marked, >2/3. Mild tumour budding was found in 54 (34%) cases, moderate in 59 (37%) cases and marked in 46 (29%) cases. The degree of budding was linked with poor tumour differentiation, lymph node metastasis and advanced TNM stage (P < 0.001). In univariate analysis, patients with marked tumour budding [5-year cancer-related survival (CRS)/recurrence-free survival (RFS), 39%/53%] had significantly worse survival [CRS, hazard ratio (HR), 4.561; 95% confidence interval (CI), 2.265-9.184; P < 0.001; RFS, HR, 3.240; 95% CI, 1.430-7.342; P = 0.005] than those with mild (5-year CRS/RFS, 80%/82%) or moderate (63%/66%) budding. In the Cox regression model, marked tumour budding (HR, 3.137; 95% CI, 1.517-6.487; P = 0.002) and advanced tumour stage (stage III, HR, 3.226; 95% CI, 1.475-7.053; P = 0.003; stage IV, HR, 24.443; 95% CI, 10.843-55.100; P < 0.001) proved to be an independent predictor of short CRS. Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in patients with colorectal carcinoma.

Tumor Budding as an Indicator of Isolated Tumor Cells in Lymph Nodes From Patients With Node-Negative Colorectal Cancer

Isolated tumor cells are often found in the regional lymph nodes of colorectal cancer, although their prognostic significance has not been established yet. This study was performed to investigate the correlation between the presence of isolated tumor cells in lymph nodes and the histopathologic characteristics of colorectal cancers and, thus, to determine which factors are associated with isolated tumor cells. We used immunohistochemistry with anticytokeratin antibody to examine 2,784 lymph nodes in 109 patients with node-negative colorectal cancers. The clinicopathologic features of the tumors with isolated tumor cells were compared with those without isolated tumor cells. The frequency, number, and level of the isolated tumor cells also were assessed. Isolated tumor cells were detected in 335 lymph nodes (12 percent) from 71 patients (65.1 percent). Those tumors having isolated tumor cells in lymph nodes, compared with those not having isolated tumor cells, were characterized by large tumor size, high T stage (pT3 and pT4), angiolymphatic invasion, perineural invasion, absence of peritumoral lymphocytic response, microsatellite instability-negative phenotype, and tumor budding. Multivariate analysis showed that those factors independently associated with the presence of isolated tumor cells were high T stage, tumor budding, and microsatellite instability-negative phenotype. Among the 71 patients with high T stage and microsatellite instability-negative phenotype, tumors with isolated tumor cells were characterized by a high frequency of tumor budding compared with tumors without isolated tumor cells (85 vs. 36.4 percent). In a further study, the degree of budding, which was assessed by an immunohistochemical study of gamma2 chain of laminin-5, was closely related to the number and location of isolated tumor cells. Moreover, we found that most of the isolated tumor cells in the regional lymph nodes also expressed gamma2 chain of laminin-5. Our results suggested that isolated tumor cells are derived from undifferentiated cancer cells or small clusters ("budding") at the invasive front. Thus, tumor budding may be used as an indicator of isolated tumor cells in lymph nodes with node-negative colorectal cancers.

An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer

We examined resected specimens from 40 cases of advanced rectal cancer to determine the extent of microtubular cancer nests and undifferentiated cancer cells (budding). We investigated the relationship between this budding and lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (n), respectively. Moreover, we examined the relationship between ly, budding, and n in the preoperative biopsy specimens of 112 patients, including those of the 40 cases mentioned above. The degree of budding, which was abundant in the actively invasive region, showed a strong correlation with the degree of ly and the existence of n in the resected specimens. Also, budding was recognized in a relatively large portion of the biopsy specimens (52 of 112 [46.4%]) and lymph node metastasis was found in 41 of 52 specimens (78.8%). In 57 specimens, neither ly nor budding was found, and 16 of these specimens (28.1%) had positive lymph nodes. These results implied that the degree of budding in the actively invasive region can be a great help in predicting the presence of n. The presence or absence of budding in preoperative biopsy specimens also can be an important factor (along with the degree of differentiation and ly) in estimating the probability of n.