Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter

Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC.

Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation

BackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.ResultsHigh-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).ConclusionThe combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.

Composite Scoring System and Optimal Tumor Budding Cut-Off Number for Estimating Lymph Node Metastasis in Submucosal Colorectal Cancer

Background Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. Methods In total, 395 patients with histologically confirmed T1N0–2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. Results The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80–36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91–11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21–7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. Conclusions For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

New morphological risk factors for metastasis to regional lymph nodes in rectal cancer with invasion into the submucosa

AIM to assess prognostic significance of pathologic features of T1 rectal carcinoma in relation to regional lymph nodes involvement (N+).MATERIAL AND METHODS: surgical specimens (n = 66) from rectal resection for carcinoma pT1 were investigated. Following prognosticators were evaluated: depth of submucosal invasion, grade of differentiation, lymphovascular invasion (LVI), tumor budding (Bd), poorly differentiated clusters (PDC) of tumor and rupture of cancer glands (CGR).RESULTS: lymph nodes metastases were found in 13 (19.7%) specimens. LVI was associated lymphatic spread in great possibility OR 38.0 95% CI 2.1-670 (p < 0.0001). Tumor budding of high grade (Bd3) OR 6.2 95% CI 1.2-31 (p < 0.0001) and poorly differentiated clusters (p = 0,03) also increased risk of lymph node metastases. Depth of submucosal invasion, grade of differentiation, and rupture of cancer glands failed to demonstrate significant association with N+. Logistic regression analysis allowed to determine LVI as independent prognostic factor of lymph node tumor involvement.CONCLUSION: lymphovascular invasion, tumor budding and poorly differentiated clusters of tumor are risk factors of T1 rectal carcinoma lymph node metastases.

Tumor budding as a prognostic criterion of colorectal cancer

Colorectal cancer (CRC) is the second leading cause of mortality among cancers after malignant tumors of respiratory system. One of the most significant prognostic features of CRC is tumor budding (TB), which isn’t widely implemented in clinical practice. The aim of this research: to find the prognostic criteria of recurrence and lethal outcome of CRR IIA and IIIB stages (рТ3N0-2M0), the ratio of tumors with certain differentiation in groups of research was taken equal. Material and methods. The group I was formed from primary CRC without recurrences. The main relapse-free survival time was 5 years (62.5 ± 16.5 months). The ІІ group – primary CRC with recurrences; ІІА – with recurrences during 5 years from the moment when the tumor was removed, without fatal outcome; ІІВ – with recurrences and lethal outcome from genera­lization of tumor process during 5 years from the moment when the tumor was removed. The microslides of CRC were made by using the standard methods. Results. TB was identified in 46.66 % (28/60) of CRC рТ3N0-2M0. The direct relationship between tumor grade and presence of TB was found (Р < 0.05), but TB didn’t define differentiation of the CRC. There was a statistically significant relationship between TB and metastatic spreading of CRC to regional lymph nodes (Р < 0.001). Metastasis was associated with 3 stage of TB, absence of metastasis was typical for CRC without TB. The tendency was found in a larger number of cases of the CRC with TB 3 stage among recurring CRC compared with CRC without recurrence, mainly due to the ІІВ group of the research. Inverse correlation between TB stage and time of recurrence appearance was found (Р < 0.05). TB in central tumor sites was followed by presence and higher stage of TB in peripheral tumor sites (Р < 0.05), that can be taken into account during biopsies of CRC. Conclusions. TB is a prognostic criterion of metastasis and time of recurrence appearance for CRC рТ3N0-2M0, which is mostly typical for tumors in patients with recurrences and lethal outcome at the taken equal ratio of tumors by differen­tiation.

Tumor Budding Score Is a Strong and Independent Prognostic Factor in Patients With Pancreatic Ductal Adenocarcinoma: An Evaluation of Whole Slide Pathology Images of Large Sections

ObjectiveWe aimed to develop the tumor budding (TB) score and to explore the association between the TB score and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsIn this retrospective study, 130 consecutive patients with PDAC underwent surgical resection between July 2016 and March 2019. The location and counts of TB were assessed based on the digitalized whole slide hematoxylin and eosin images. The TB score was achieved using the Cox regression equation. The cutoff point for the TB score was determined by X-tile. Univariate and multivariate Cox regression models were used to analyze the association between the TB score and OS.ResultsThe TB score was 0.49 (range = 0–1.08), and the best cutoff for the TB score was 0.62. The duration of survival in individuals with a low TB score [median = 21.8 months, 95% confidence interval (CI) = 15.43–25.50] was significantly longer than that in those with a high TB score (median = 11.33 months, 95% CI = 9.8–14.22). Univariate analysis revealed that the TB score was significantly associated with OS [hazard ratio (HR) = 2.71, 95% CI = 1.48–4.96, p = 0.001]. Multivariate analysis revealed a strong and independent association between the TB score and OS (HR = 2.35, 95% CI = 1.27–4.33, p = 0.03). The high TB score group had a 2.14 times higher mortality than the low TB score group.ConclusionThe TB score is strongly and independently associated with the risk of OS in PDAC.