Immunohistochemical analysis of tumor budding in stage II colon cancer: exploring zero budding as a prognostic marker.

Tumor budding, a biomarker traditionally evaluated using hematoxylin and eosin (H&E) staining, has gained recognition as a prognostic biomarker for stage II colon cancer. Nevertheless, while H&E staining offers valuable insights, its limitations prompt the utilization of pan-cytokeratin immunohistochemistry (IHC). Consequently, this study seeks to evaluate the prognostic significance of tumor budding using IHC in a contemporary cohort of stage II colon cancer patients, aiming to deepen our understanding of this critical facet in cancer prognosis. We conducted a retrospective, population-based cohort study including 493 patients with stage II colon cancer and evaluated tumor budding using IHC, following the H&E-based guidelines proposed by the International Tumor Budding Consensus Conference Group. Correlation between H&E-based and IHC-based tumor budding was assessed using a four-tiered scoring system that included a zero budding (Bd0) category. Survival analyses explored the prognostic significance of tumor budding assessed by IHC and H&E. As expected, IHC-based tumor budding evaluation yielded significantly higher bud counts compared to H&E (p < 0.01). Interestingly, 21 patients were identified with no tumor budding using IHC. This was associated with significantly improved recurrence-free survival (HR = 5.19, p = 0.02) and overall survival (HR = 4.47, p = 0.04) in a multivariate analysis when compared to tumors with budding. The Bd0 category demonstrated a 100% predictive value for the absence of recurrence. In conclusion, IHC-based tumor budding evaluation in stage II colon cancer provides additional prognostic information. The absence of tumor budding is associated with a favorable prognosis and may serve as a potential marker for identifying patients with no risk of recurrence.

Tumor budding - a potential biomarker in low grade salivary gland carcinomas?

Background: Low-grade salivary gland carcinoma is regularly treated with surgical therapy of the salivary gland without elective neck dissection in T1/2 carcinomas, either alone or with adjuvant radiation therapy. However, occult metastasis and locoregional recurrence influence therapy and outcome. Tumor budding is an emerging prognostic pathological factor in many carcinomas, but has not yet been adequately considered in salivary gland carcinomas. Methods: We conducted a retrospective single-center study of 64 patients diagnosed with low-grade carcinoma of the major salivary glands treated between 2003 and 2017. Pathological risk factors and TNM classification were thoroughly assessed for each case. All hematoxylin and eosin (HE)-stained histological specimens underwent careful examination, and tumor budding was identified following the guidelines set forth by the International Tumor Budding Consensus Conference in 2016. Results: Tumor budding was not statistically significant concerning 5-year survival rate (5-YSR) (p=0.969) and mean overall survival (log-rank p=0.315). Whereas 5-year disease-free survival rate (5-YDFSR) was 87% in the low tumor budding group and 61.1% in the intermediate and high tumor budding group (p=0.021). Mean disease-free survival accounted for 100.2 months (CI: 88.6;111.9) in the low budding score group and 58.7 months (CI: 42.8;74.6) in the other group (log-rank p=0.032). Notably, pT1/2 showed significantly lower tumor buds than pT3/4 stages (2.43 tumor buds/0.785 mm2 vs. 4.19 tumor buds/0.785 mm2, p=0.034). Similar findings were noted comparing nodal-positive and nodal-negative patients, as well as patients with and without lymphovascular invasion and perineural invasion (each p<0.05). Conclusions: Tumor budding might be used as an additional prognostic factor for recurrence in low-grade salivary gland carcinoma, seemingly associated with a higher nodal metastasis rate and advanced tumor stages and a worse 5-YDFSR. Consequently, the evaluation of tumor budding in resection specimens of low-grade salivary gland tumor may prove valuable in decision-making for neck dissection and follow-up strategy.

Prognostic significance of micronest in cancer stroma in resected lung squamous cell carcinoma.

Tumor budding in the cancer stroma has been reported to be a prognostic factor in non-small cell lung cancer. Micronest in cancer stroma (MICS) is often observed as a formation that is larger and more conspicuous than budding, but its clinicopathologic significance is unclear. In this study, we aimed to examine the clinicopathological significance of MICS in lung squamous cell carcinoma (LSqCC). A total of 198 consecutive patients with pathologically diagnosed LSqCC (anyT N0-1M0) were enrolled in this study. MICS were defined as those that met the following criteria: (1) consisting of 5-200 tumor cells or less than 200 µm in diameter and (2) more than 200 µm away from the adjacent main lesion. The prognostic impact of the presence or absence of MICS and the characteristics of MICS-forming cancer cells were evaluated by immunohistochemistry (IHC). MICS was observed in 57 patients (28.8%), and overall survival (OS) and recurrence-free survival (RFS) were significantly shorter in the MICS-positive group (OS: 44.4% vs. 84.4%, p < 0.001; RFS: 30.0% vs. 82.6%, p < 0.001). Univariate and multivariate analyses revealed that the presence of MICS was an independent poor prognostic factor for OS (hazard ratio [HR] 3.54, p < 0.001) and RFS (HR 4.99, p < 0.001). Immunohistochemistry showed that the expression levels of the cell-cell adhesion molecule E-cadherin and hypoxia-induced protein GLUT-1 were significantly decreased in cancer cells forming MICS lesions compared to the tumor component excluding MICS within the same tumor (non-MICS lesions). Our data show that MICS is a distinct morphological feature with important biological and prognostic significance.

Analyzing Tumor Budding Scores in Invasive Breast Carcinoma: A Tertiary Care Center Study in South India.

Introduction and Aim: Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has garnered attention due to its potential implications for prognosis, treatment strategies, and our understanding of cancer progression. Our aim is to study the distribution of tumor buds and its scoring in patients with infiltrating breast carcinoma and to associate with other histopathological parameters like the size of the tumor, its grade, lymphovascular invasion, and lymph node metastasis. Materials and Methods: This was a study analyzing the data of 70 resected specimens of primary breast carcinomas and providing a descriptive overview. Tumor budding was recognized, counted, and graded in hematoxylin and eosin slides. The cases were classified as low (0-4), intermediate (5-9), and high (≥10 buds) based on the count of tumor buds. Tumor budding has significant correlation with tumor grade and tumor size. Results: Of the 70 cases, 60 cases (85.71%) were diagnosed as invasive ductal carcinoma NOS. The majority [38 (54.28%)] of the cases showed an intermediate tumor budding score of 5-9/10 HPF. Conclusion: Evaluation of tumor budding allows pathologists and oncologists to gather valuable information about the tumor's biological aggressiveness and potential for metastasis. It also helps in better risk stratification of patients, enabling a more personalized and tailored approach to treatment planning. In conclusion, assessing tumor budding in breast carcinoma holds significant clinical importance in the management and prognosis of this disease.

Tumor budding is a prognostic marker for overall survival and not for lymph node metastasis in Oral Squamous Cell Carcinoma - Systematic Review Update and Meta-Analysis.

Objective: Tumor budding (TB) has shown promising results as a prognostic marker in several cancers such as colorectal carcinoma, breast carcinoma etc. It has been co-related to aggressiveness of the tumor and can also predict the metastasis to the lymph nodes. This systematic review evaluates the prognostic potential of TB in predicting lymph node metastasis (LNM) in OSCC. Data sources: Systematic search was carried out in the electronic data-bases i.e. PubMed, Cochrane and Google scholar for original studies related to TB in OSCC. The assessment of risk bias was done using QUIPS tool. Meta-analysis was done using STATA software. Results: A total of 25 articles were included. A significant association was noted for overall survival and prognosis but not for TB LNM in OSCC. Meta-analysis revealed a pooled estimate i.e odds ratio of 2.10 (CI - 0.00 - 4.20) for TB and LNM while for overall survival, it was 2.29 (CI-1.81-2.76). Conclusion: Tumor budding though is strongly associated with LNM in OSCC did not show significant relationship in this systematic review but demonstrated a higher correlation with overall survival. It highlights that TB is an important parameter for prognosis of oral cancer but its potential in prediction of LNM needs further validation.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study.

BACKGROUND: Lymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions. METHODS: A retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored. RESULTS: The TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively. CONCLUSIONS: TB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.

Tumor budding is an optimal indictor of occult cervical metastasis in clinical early-stage buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC. METHODS: Seventy-one cT1-2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively. RESULTS: Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94-116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS. CONCLUSIONS: The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.

The Relationship between Tumor Budding and Tumor Deposits in Patients with Stage III Colorectal Carcinoma.

Background/Objectives: Recently, some new morphological features of colorectal cancer have been discovered as important prognostic factors; in this paper, we study the relationship between tumor budding (TB) and tumor deposits (TDs). Methods: The retrospective cohort study included 90 patients with pathohistologically confirmed stage III CRC who were treated with radical surgical resection. All hematoxylin and eosin (H and E)-stained slides from each patient were reviewed, and histological parameters were recorded. The samples were divided into two groups with similar sizes: a group without TDs (N = 51) and a control group with TDs (N = 39). The presence and TB grade were further analyzed in these groups and compared with other clinical and histological features. Results: The prevalence of TB in the investigated cohort was unexpectedly high (94.4%). Overall, there were 23 (25.6%) Bd1, 20 (22.2%) Bd2, and 47 (52.2%) Bd3 cases. The presence of TDs was significantly associated with a higher number of TB (p < 0.001, OR 16.3) and, consequently, with a higher TB grade (p = 0.004, OR 11.04). A higher TB grade (p = 0.001, HR 2.28; 95% CI 1.93-4.76) and a growing number of TDs (p = 0.014, HR 1.52; 95% CI 1.09-2.1) were statistically significantly associated with shorter survival. Conclusions: TDs appear more often in patients with higher TB grades in stage III CRC. A higher TB grade and a growing number of TDs were statistically significantly associated with shorter overall survival. These results could give additional emphasis to the importance of TB as an adverse prognostic factor since a strong relationship with TDs has been demonstrated.

Enhancing Colorectal Cancer Tumor Bud Detection Using Deep Learning from Routine H&E-Stained Slides.

Tumor budding refers to a cluster of one to four tumor cells located at the tumor-invasive front. While tumor budding is a prognostic factor for colorectal cancer, counting and grading tumor budding are time consuming and not highly reproducible. There could be high inter- and intra-reader disagreement on H&E evaluation. This leads to the noisy training (imperfect ground truth) of deep learning algorithms, resulting in high variability and losing their ability to generalize on unseen datasets. Pan-cytokeratin staining is one of the potential solutions to enhance the agreement, but it is not routinely used to identify tumor buds and can lead to false positives. Therefore, we aim to develop a weakly-supervised deep learning method for tumor bud detection from routine H&E-stained images that does not require strict tissue-level annotations. We also propose Bayesian Multiple Instance Learning (BMIL) that combines multiple annotated regions during the training process to further enhance the generalizability and stability in tumor bud detection. Our dataset consists of 29 colorectal cancer H&E-stained images that contain 115 tumor buds per slide on average. In six-fold cross-validation, our method demonstrated an average precision and recall of 0.94, and 0.86 respectively. These results provide preliminary evidence of the feasibility of our approach in improving the generalizability in tumor budding detection using H&E images while avoiding the need for non-routine immunohistochemical staining methods.

Tumor Budding, p53, and DNA Mismatch Repair Markers in Sinonasal Intestinal-Type Adenocarcinoma: A Retrospective Study Supports the Adverse Prognostic Impact of Tumor Budding.

Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients' outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice.

Clinico-pathological evaluation of tumor budding in the oncological progression of colorectal cancer. / Evaluación clínico-patológica del tumorbudding en la progresión oncológica del cáncer colorrectal.

INTRODUCTION: Tumor budding (TB), defined as the presence of individual neoplastic cells or isolated groups of up to 4 cells at the front of tumor invasion, has become an adverse prognostic marker in colorectal cancer (CRC) in recent decades. The prognostic impact of TB in CRC remains not clearly defined and histological methods for its evaluation vary depending on the center. The objective of this study is to investigate the association between TB and CRC, in terms of oncological evolution and pathological stage. METHODS: A retrospective observational study was conducted, including patients undergoing curative oncological surgery for CRC between January 2017 and December 2022. The effects of TB on disease-free survival (DFS) and overall survival (OS) were evaluated according to the Kaplan-Meier curves. RESULTS: In 78 cases TB was described in the pathology report. TB was present in 56 patients (71.8%), divided into the following categories: low grade in 22 (39.3%), intermediate grade in 17 (30.4%) and high grade in 17 (30.4%). The proportion of patients who presented lymph node metastases, lympho-vascular and perineural invasion was significantly higher in patients with TB (26.8% vs 0%, P=.008; 41.1% vs 4.5%, P=.002; 16.1% vs 0% P=.054; respectively). DFS was 86.3% in low-grade TB, 75.3% in intermediate-grade TB, and 70.3% in high-grade TB. Cases with intermediate and high grade were associated with a shorter OS compared to the low grade group (93.7% and 75.4% vs 100% P=.012, respectively). CONCLUSION: These results suggest that TB expression may be a useful risk factor as a prognostic factor for the detection of lymph node metastasis, local recurrence, and distant metastasis in CRC.

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer.

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their "mosaic" CDX2 expression pattern.

The impact of tumor budding and single-cell invasion on survival in patients with stage III/IV locally advanced oral squamous cell carcinoma- results from a prospective cohort study.

Introduction: Tumor budding (TB) refers to the presence of small clusters of tumor cells at the invasive front of a malignant tumor. Single tumor cell invasion (SCI) is an extreme variant of TB, in which individual loose tumor cells are present at the invasive front. Both TB and SCI are important histomorphologic risk factors postulated to indicate loss of cellular cohesion. In this study, we investigated the influence of TB and SCI on different survival outcomes in patients with locally advanced oral squamous cell carcinoma (OSCC). Methods: We included 129 patients with locally advanced OSCC (pT3-4) from a single-center, prospectively maintained cohort. We examined the association of TB and SCI with the presence of occult lymph node metastasis using a logistic regression model. Survival probabilities were estimated using the Kaplan-Meier method and cumulative incidence functions. The association of TB and SCI on overall survival (OS), oral cancer-specific survival (OCSS), and local recurrence-free survival (LRFS) was investigated using Cox's proportional hazards regression models. Results: TB was detected in 98 (76%) of the tumors, while SCI was observed in 66 (51%) patients. There was a significant association between TB and the occurrence of occult lymph node metastasis (OR=3.33, CI: 1.21-10.0). On multivariate analysis, TB had no detectable impact on survival outcomes. However, SCI showed a higher risk for local recurrence (Hazards ratio (HR): 3.33, CI: 1.19 - 9.27). Discussion: This study demonstrates that TB and SCI in locally advanced OSCC function as an independent risk factor for occult lymph node metastases, as well as local recurrences. Both histomorphologic risk factors could serve as an additional parameter for stratifying therapy and escalating multimodal treatment approaches.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

PURPOSE: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors. METHODS: We analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients). RESULTS: 64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352). CONCLUSION: Our study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts.

Keratin 6A Is Expressed at the Invasive Front and Enhances the Progression of Colorectal Cancer.

Keratins (KRTs) are intermediate filament proteins in epithelial cells, and they are important for cytoskeletal organization. KRT6A, classified as a type II KRT, is normally expressed in stratified squamous epithelium and squamous cell carcinomas. Little is known about the expression and role of KRT6A in adenocarcinomas. We investigated the clinicopathologic and molecular biological significance of KRT6A in colorectal adenocarcinoma. Immunostaining of colorectal adenocarcinoma cases treated at our institution demonstrated that KRT6A showed significantly stronger expression at the invasive front than that at the tumor center (P < .0001). The high KRT6A-expression cases (n = 47) tended to have a high budding grade associated with significantly worse prognoses. A multivariate analysis revealed that the KRT6A expression status was an independent prognostic factor for overall survival (P = .0004), disease-specific survival (P = .0097), and progression-free survival (P = .0033). The correlation between KRT6A and patient prognoses was also validated in an external cohort from a published data set. To determine the function of KRT6A in vitro, KRT6A was overexpressed in 3 colon cancer cell lines: DLD-1, SW620, and HCT 116. KRT6A overexpression increased migration and invasion in DLD-1 but did not in SW620 and HCT116. In 3-dimensional sphere-forming culture, KRT6A expression enhanced the irregular protrusion around the spheroid in DLD-1. Our findings in this study indicated that KRT6A expression is a valuable prognostic marker of colorectal cancer and KRT6A may be involved the molecular mechanism in the progression of invasive areas of colorectal cancer.

Few-shot Tumor Bud Segmentation Using Generative Model in Colorectal Carcinoma.

Current deep learning methods in histopathology are limited by the small amount of available data and time consumption in labeling the data. Colorectal cancer (CRC) tumor budding quantification performed using H&E-stained slides is crucial for cancer staging and prognosis but is subject to labor-intensive annotation and human bias. Thus, acquiring a large-scale, fully annotated dataset for training a tumor budding (TB) segmentation/detection system is difficult. Here, we present a DatasetGAN-based approach that can generate essentially an unlimited number of images with TB masks from a moderate number of unlabeled images and a few annotated images. The images generated by our model closely resemble the real colon tissue on H&E-stained slides. We test the performance of this model by training a downstream segmentation model, UNet++, on the generated images and masks. Our results show that the trained UNet++ model can achieve reasonable TB segmentation performance, especially at the instance level. This study demonstrates the potential of developing an annotation-efficient segmentation model for automatic TB detection and quantification.

Adapting SAM to Histopathology Images for Tumor Bud Segmentation in Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer in the United States. Tumor Budding (TB) detection and quantification are crucial yet labor-intensive steps in determining the CRC stage through the analysis of histopathology images. To help with this process, we adapt the Segment Anything Model (SAM) on the CRC histopathology images to segment TBs using SAM-Adapter. In this approach, we automatically take task-specific prompts from CRC images and train the SAM model in a parameter-efficient way. We compare the predictions of our model with the predictions from a trained-from-scratch model using the annotations from a pathologist. As a result, our model achieves an intersection over union (IoU) of 0.65 and an instance-level Dice score of 0.75, which are promising in matching the pathologist's TB annotation. We believe our study offers a novel solution to identify TBs on H&E-stained histopathology images. Our study also demonstrates the value of adapting the foundation model for pathology image segmentation tasks.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

In this editorial, we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. We focused on identifying risk factors for lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC) patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients, thereby helping to guide the selection of an appropriate treatment plan. The current standard treatment for SESCC is radical esophagectomy with lymph node dissection. However, esophagectomy is associated with considerable morbidity and mortality. Endoscopic resection (ER) offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome. However, since ER is a localized treatment that does not allow for lymph node dissection, the risk of LNM in SESCC limits the effectiveness of ER. Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy. Previous studies have shown that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular invasion are factors associated with LNM in patients with SESCC. In addition, tumor budding is commonly associated with LNM, recurrence, and distant metastasis, but this topic has been less covered in previous studies. By comprehensively evaluating the above risk factors for LNM, useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Predicting prognosis in intrahepatic cholangiocarcinoma by the histopathological features.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS: Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS: A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION: High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.