Degree Of Tumor Differentiation Research Articles

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

Whole-volume diffusion kurtosis magnetic resonance (MR) imaging histogram analysis of non–small cell lung cancer: correlation with histopathology and degree of tumor differentiation

Whole-volume diffusion kurtosis magnetic resonance (MR) imaging histogram analysis of non–small cell lung cancer: correlation with histopathology and degree of tumor differentiation

Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status

BackgroundThe status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. MethodsWe included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. ResultsAmong the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. ConclusionsOur study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

Neuroendocrine Carcinoma of the Rectum as a Cause of Acute Obstructive Abdomen. Case Report and Literature Review

Rectal neuroendocrine carcinoma, though rare, is experiencing an increase in its incidence, representing approximately 1% of all colorectal cancers. A growth in its incidence has been observed in recent decades, albeit with varying figures geographically. Research studies such as those by Dasari et al. (2017) and Scherübl et al. (2014) have indicated a significant rise in the incidence of these tumors, especially in the United States and Europe. Although it can manifest in different age groups, it is more common in middle-aged or older adults, without a clear gender predilection. Symptoms may include changes in bowel habits, rectal bleeding, abdominal pain, unexplained weight loss, and fatigue, varying according to the degree of tumor differentiation and the presence of metastasis. We present the case of a 65-year-old woman who presented with obstructive symptoms and was subsequently found to have neuroendocrine tumor post-surgery.

Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients' serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

CORRELATION OF Ki-67 CELL PROLIFERATION MARKER EXPRESSION WITH AGE,&#x0D; SEX, DISEASE STAGE, AND TUMOR DIFFERENTIATION IN GASTRIC CANCER

Relevance: Gastric cancer continues to lead the cancer incidence structure. One of the directions of a comprehensive plan to reduce the&#x0D; incidence of malignant neoplasms is the development a highly efficient early diagnostics based on the relationship between the expression of&#x0D; the cell proliferation marker Ki-67 in gastric cancer with age, sex, stage of the disease and the degree of tumor differentiation according to&#x0D; immunohistochemical analysis.&#x0D; The study aimed to study the relationship between the expression of the Ki-67 marker in gastric cancer and age, sex, stage of the disease,&#x0D; and the degree of tumor differentiation.&#x0D; Methods: The research design is a comparative descriptive study. For the study, surgical material was used from 109 patients with gastric&#x0D; cancer stages 0-IIIC, obtained during gastric cancer operations from the pathology department of the West Kazakhstan Marat Ospanov&#x0D; Medical University (WKMOMU) Medical Center from 2021 to 2022. Histological and immunohistochemical studies were conducted at the&#x0D; morphological laboratory of the Department of Histology of WKMOMU. The obtained data was statistically processed.&#x0D; Results: The present study showed a significant statistical correlation between the Ki-67 level and the histopathological grade of gastric&#x0D; cancer (p=0.039).&#x0D; The indicators such as ‘pTNM stage’ (p=0.894), ‘Age’ (p=0.664), ‘Sex (F – 1, M – 2)’ (p=0.928), and ‘Tumor localization (cardiac – 1, body – 2,&#x0D; antral and pyloric – 3)’ (p=0.866) did not statistically significantly correlated with the Ki-67 expression level.&#x0D; Conclusions: The relationship between Ki-67 expression and histopathological grade (p=0.039) in gastric cancer helps identify patients&#x0D; with aggressive tumors that require adjuvant therapy.

Immunohistochemical characteristics of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

The epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pancreatic ductal adenocarcinoma (PDAC). There are insufficient and contradictory data in the scientific literature on the peculiarities of epithelial and mesenchymal marker expression in PDAC ducts and EMT zone, which requires further research on the role of EMT in the development and progression of PDAC. Aim: to conduct a comprehensive assessment of epithelial and mesenchymal markers of EMT in the PDAC ducts and EMT zone at different degrees of differentiation. Materials and methods. A comprehensive pathomorphological and immunohistochemical examination including 49 cases of surgical material from patients with PDAC, divided into groups of moderate (G2) and low degree of tumor differentiation (G3). Results. PDAC was characterized by low levels of E-cadherin expression in both ducts and EMT – Me = 22.58 % [12.81; 36.23] and Me = 25.17 % [19.04; 35.37], respectively (p &gt; 0.05). Only membrane expression of the marker was detected in the ducts and membrane-cytoplasmic one – in the EMT zone without significant differences in the groups. There was a significant decrease in the ductal β-catenin expression (p &lt; 0.05) in G2 with membrane-cytoplasmic staining (Me = 15.58 % [10.42; 26.24]), in G3 – with membrane (Me = 4.42 % [2.35; 5.93]); in the EMT zone, only membrane-cytoplasmic expression was observed in both groups without significant difference (p &gt; 0.05). Membrane expression of CK7 was positive in 100 % of PDAC, significantly lower at G2 (Me = 19.51 % [10.70; 27.24]; Me = 26.19 % [20.93; 30.05], p &lt; 0.05), and CK18 (Me = 21.34 % [9.68; 29.96] – in G2, in G3 – Me = 22.50 % [8.24; 40.08], p &gt; 0.05). Expression of α-SMA and Vim was seen in spindle-shaped stromal cells, around tubular and trabecular structures with membrane-cytoplasmic staining. There was no significant difference between α-SMA in G2 and G3, the level of vimentin was significantly lower in G3 (p &lt; 0.05). Conclusions. The features of PDAC E-cadherin, β-catenin, CK7 and CK18 marker expression indicate a greater EMT process at the periphery of the tumor and its severity increases with tumor progression. The optimal markers to determine the mesenchymal phenotype of PDAC cells are α-SMA and vimentin.

Expression of E-Cadherin and N-Cadherin in the Endocervix as a Predictive Factor in Patients with Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecological malignancy. This study aimed to evaluate the expression of E-cadherin and N-cadherin in primary endometrial lesions and the endocervix in patients with EC to identify noninvasive predictive factors. In this single-center retrospective study, data on 101 patients who underwent surgery for EC were collected. The immunohistochemical expression of E-cadherin and N-cadherin was assessed depending on the tumor grade, location, and cell differentiation. Correlations between E-cadherin and N-cadherin levels in the endocervix and the primary tumor were determined. The degree of histological tumor differentiation significantly affected E-cadherin expression (p = 0.04) but had no impact on N-cadherin levels. In type II EC, the expression of both cadherins in the tumor tissue differed from their endocervical levels. The expression of E-cadherin differed significantly between the endocervix (p < 0.001) and the tumor (p = 0.001), depending on the type of EC. The expression of E-cadherin was related to the N-cadherin level only in the endocervix in patients with type II EC (p = 0.02). E-cadherin and N-cadherin were expressed in the endocervix in patients with EC. The expression of cadherins, determined during cervical cytology, may be a valuable clinical marker of EC.

Clinicopathological Correlation of P53 Protein Expression in different Histological Subtypes of Gastric Carcinoma

Introduction: Gastric cancer is one of the common cancers after lung cancer worldwide, especially in the developing countries. p53 immunohistochemical expression has been proposed as a potential tool to evaluate the biological behavior of gastric cancer. However, its practical implication in gastric cancer prognosis or treatment by restoration of mutated p53 function is yet to be fully exploited. Hence, this study with the aim of assessing the yield of p53 expression in gastric carcinoma and its relationship with various clinicopathological parameters was formulated. Objectives: To assess immunohistochemical expression of p53 protein in different histological subtypes of gastric carcinoma cases and to study correlation between p53 protein expression and different clinicopathological parameters like age, gender, tumour location, gross pattern, histological types, degree of tumor differentiation and pathological staging in the above said cases. Materials and Methods: This was a hospital based cross-sectional study done over a period of 18 months on 60 cases of gastrectomies with proven histological diagnosis of gastric carcinoma. Observation and Results: Strong p53 expression was frequent among elderly male patients (&gt;60 years) who had ulceroproliferative tumors, located at pyloric antrum belonging to pTNM stage IIIA. In 87% cases, it was expressed, predominantly in moderately differentiated intestinal type with serosal invasion. Also, cases even with no lymph node metastasis showed p53 expression. Conclusion: Few findings were contradictory to other similar studies e.g. lymph node negative cases showing P53 expression does not support the hypothesis of predicting lymph node status by p53 expression. No significant correlation between p53 expression and different clinicopathological parameters in gastric carcinoma cases was seen. Keywords: P53, immunohistochemical, clinicopathological, histological subtypes, metastasis

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer: A retrospective analysis.

Lung cancer (LC) is a global medical, social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms. LC is characterized by an aggressive course, and in the presence of disease recurrence risk factors, patients, even at an early stage, may be indicated for adjuvant therapy to improve survival. However, combined treatment does not always guarantee a favorable prognosis. In this regard, establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness. To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma (LSCC). A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018. Postoperatively, all patients received adjuvant chemotherapy. Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope. Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence. Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence. Survival was analyzed using the Kaplan-Meier method. The log-rank test was used to compare survival curves between patient subgroups. Differences were considered to be significant at P < 0.05. The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established: a low degree of tumor differentiation [odds ratio (OR) = 7.94, 95%CI = 1.08-135.81, P = 0.049]; metastases in regional lymph nodes (OR = 5.67, 95%CI = 1.09-36.54, P = 0.048); the presence of loose, fine-fiber connective tissue in the tumor stroma (OR = 21.70, 95%CI = 4.27-110.38, P = 0.0002); and fragmentation of the tumor solid component (OR = 2.53, 95%CI = 1.01-12.23, P = 0.049). The area under the curve of the predictive model was 0.846 (95%CI = 0.73-0.96, P < 0.0001). The sensitivity, accuracy and specificity of the method were 91.8%, 86.9% and 75.0%, respectively. In the group of patients with a low risk of LSCC recurrence, the 1-, 2- and 5-year disease-free survival (DFS) rates were 84.2%, 84.2% and 75.8%, respectively, while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%, 40.1% and 8.2%, respectively (P < 0.00001). Accordingly, in the first group of patients, the 1-, 2- and 5-year overall survival (OS) rates were 94.7%, 82.5% and 82.5%, respectively, while in the second group of patients, the OS rates were 89.8%, 80.1% and 10.3%, respectively (P < 0.00001). The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

PET-CT with 18F-FDG in Gynecological Malignancies. Prognostic Significance of the Standardized Uptake Value

"Gynecologic cancers are among the most common cancers in women and are a significant cause of mortality in women worldwide. FDG-PET images play a critical role in several areas of oncology and are an essential tool for the diagnosis and staging of gynecologic cancer, providing information about tumor metabolism. Aim: The aim of this study was to investigate the relationship between tumor differentiation, type of malignancy, and glucose metabolism in patients with confirmed gynecologic cancer. Materials and Methods We performed a retrospective review of 60 consecutive patients (ages 31-76) with histopathologically confirmed gynecologic cancer who underwent PET-CT in our department between January 2021 and March 2022. Quantitative data on glucose metabolism were collected using the maximum standardized uptake value normalized by lean body mass (SULmax). We reviewed a total of 60 patients with a mean age of 60±9 years, and a median of 62. Results: 14 patients were diagnosed with cervical cancer, 20 with endometrial cancer, and 26 with ovarian cancer; 13 patients had well-differentiated cancer, 11 had moderately differentiated cancer, and 36 had poorly differentiated cancer. A positive correlation was observed between the measured SULmax and the degree of tumor differentiation, indicating higher glucose uptake in poorly differentiated cancer. When examining the relationship between the type of cancer and SULmax, we found that endometrial cancer exhibited the highest mean SULmax (8.36±6.75), followed by ovarian cancer and cervical cancer. Additionally, we noted that glucose uptake was higher in patients aged over 62 years. Regardless of the tumor differentiation, the findings in endometrial cancer showed the highest mean SUVmax values in all grades of tumor differentiation. Conclusion: Our study showed that glucose consumption correlates not only with the degree of differentiation but also with age and type of tumor, with the highest values in patients older than 62 years with endometrial cancer. Given the correlation between glucose consumption and tumor aggressiveness, this finding may be important for prognostic evaluation of patients with gynecologic malignancies."

Predictive models based on machine learning for early recurrence and metastasis in postoperative patients with colorectal cancer

Abstract Objectives: To construct and validate a prediction model based on machine learning algorithms for early recurrence and metastasis in patients with colorectal cancer after surgery. Methods: This study employed a prospective cohort design. A total of 498 postoperative patients with colorectal cancer, treated at an affiliated hospital of Qingdao University, were recruited using convenience sampling from June to December 2021. Data were collected during outpatient visits and hospitalizations. The risk factors for early recurrence and metastasis of colorectal cancer were determined through multivariate logistic regression analysis in SPSS 26.0 software. Using Python 3.7.0 software, 4 machine learning algorithms (logistic regression, Support Vector Machine, XGBoost, and LightGBM) were used to develop and validate prediction models for early recurrence and metastasis of colorectal cancer after surgery. Results: Of the 498 patients, 51 (10.24%) had early recurrence and metastasis. Multivariate logistic regression analysis showed that personal traits (family history of cancer, histologic type, degree of tumor differentiation, number of positive lymph nodes, and T stage), behavior and/or lifestyle (intake of refined grains, whole grains, fish, shrimp, crab, and nuts, as well as resilience), and interpersonal networks (social support) were all associated with early recurrence and metastasis of colorectal cancer (P&lt;0.05). The logistic regression prediction model showed the best prediction performance out of the 4 models, with an accuracy rate of 0.920, specificity of 0.982, F1 of 0.495, AUC of 0.867, Kappa of 0.056, and Brier score of 0.067. Conclusion: Our findings suggest that a prediction model based on logistic regression could accurately and scientifically predict which patients are likely to experience early recurrence and metastasis, helping to lessen the burden for both patients and the health care system.

Prognostic modeling for nasopharyngeal carcinoma (NC) undergoing concurrent chemoradiotherapy using clinical and enhanced MRI-Delta radiomics data: A preliminary study.

Nasopharyngeal carcinoma (NC) is one of the prevalent malignancies of the head and neck region with poor prognosis. The aim of this study is to establish a predictive model for assessing NC prognosis based on clinical and MR radiomics data, subsequently to develop a nomogram for practical application. Retrospective analysis was conducted on clinical and imaging data collected between May 2010 and August 2018, involving 211 patients diagnosed with histologically confirmed NC who received concurrent chemoradiotherapy or radical surgery in Xiangyang No. 1 People's Hospital. According to 5-10 years of follow-up results, the patients were divided into two groups: the study group (n= 76), which experienced recurrence, metastasis, or death, and the control group (n= 135), characterized by normal survival. Training and testing subsets were established at a 7:3 ratio, with a predefined time cutoff. In the training set, three prediction models were established: a clinical data model, an imaging model, and a combined model using the integrated variation in clinical characteristics along with MR radiomics parameters (Delta-Radscore) observed before and after concurrent chemoradiotherapy. Model performance was compared using Delong's test, and net clinical benefit was assessed via decision curve analysis (DCA). Then, external validation was conducted on the test set, and finally a nomogram predicting NC prognosis was created. Univariate analysis identified that the risk factors impacting the prognosis of NC included gender, pathological type, neutrophil to lymphocyte ratio (NLR), degree of tumor differentiation, MR enhancement pattern, and Delta-Radscore (P< 0.05). The combined model established based on the abovementioned factors exhibited significantly higher predictive performance [AUC: 0.874, 95% CI (0.810-0.923)] than that of the clinical data model [AUC: 0.650, 95% CI (0.568-0.727)] and imaging model [AUC: 0.824, 95% CI (0.753-0.882)]. DCA also demonstrated superior clinical net benefit in the combined model, a finding further verified by results from the test set. The developed nomogram, based on the combined model, exhibited promising performance in clinical applications. The Delta-Radscore derived from MR radiomics data before and after concurrent chemoradiotherapy helps enhance the performance of the NC prognostic model. The combined model and resultant nomogram provide valuable support for clinical decision-making in NC treatment, ultimately contributing to an improved survival rate.

Association between Heavy Metals and Trace Elements in Cancerous and Non-cancerous Tissues with the Risk of Colorectal Cancer Progression in Northwest China.

Alterations in heavy metals and trace element levels may be associated with various cancers. However, the role of this interaction in colorectal cancer (CRC) progression is unclear. In recent years, Principal Component Analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) models have provided new ideas for analyzing the effects of metal mixtures on CRC progression. Herein, we assessed the differences in the levels of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), nickel (Ni), selenium (Se), and zinc (Zn) in tumors and adjacent healthy tissues, to investigate the relationship between heavy metals/trace elements and CRC progression. Surgical samples of CRC and noncancerous tissues were collected, and trace metal levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression, PCA, and BKMR models were used to investigate the relationship between heavy metals and trace elements and the degree of tumor differentiation and lymph node metastasis in CRC. Cancer tissues showed lower As, Cd, Co, and Cr concentrations, and higher Se concentrations than healthy tissues (P < 0.05). In addition, CRC patients with poorly differentiated tumors and/or positive lymph node metastases had lower levels of Cd, Zn, Cu, and Se (P < 0.05). Logistic regression showed that single metal concentration was negatively correlated with CRC progression. PCA and BKMR models also showed that the metal mixture concentration was negatively correlated with CRC progression, with Cd contributing the most. Overall, changes in heavy metal and trace element levels may be related to the development of CRC; however, further mechanistic studies are required.

CircBRIP1: a plasma diagnostic marker for non-small-cell lung cancer

BackgroundCircular RNA (circRNA), which has been demonstrated in studies to be abundantly prevalent in tumor cells and bodily fluids and to play a significant role in tumors, has the potential for biological markers to be used to assist tumor diagnosis. This study mainly discusses the potential of circBRIP1 as a biomarker for diagnosing non-small-cell lung cancer (NSCLC).MethodsFirst, high-throughput sequencing screened the differentially expressed circBRIP1, and real-time fluorescence quantitative PCR (qRT-PCR) verified its expression in NSCLC. Next, sanger sequencing, agarose gel electrophoresis, RNase R assay, and fluorescence in situ hybridization (FISH) were used to verify its molecular characteristics. The diagnostic value was analyzed by the subject operating characteristic curve (ROC), and the cardinality test was analyzed for correlation with clinicopathological parameters. Finally, we tentatively predicted the downstream miRNA- or RNA-binding protein that may bind to circBRIP1.ResultsCircBRIP1 is highly expressed in NSCLC tissues, cells and plasma with good specificity and stability. CircBRIP1 not only can well-distinguish NSCLC patients from benign pulmonary diseases (BPD) patients, healthy individuals and small cell lung cancer (SCLC) patients, but it also has some potential for dynamic monitoring. Combined with the analysis of clinicopathological data, the high level of circRNA expression was related to the degree of tumor differentiation, TNM stage, T stage, lymph node metastasis and distal metastasis in NSCLC patients. In addition, circBRIP1 has a high diagnostic value.ConclusionsPlasma circBRIP1 is significantly overexpressed in NSCLC patients. It can be used as a sensitive biomarker with unique value for early diagnosis, tumor development and prognosis detection.

Clinical Significance of HHLA2 as a Novel Therapeutic Target for Colorectal Cancer.

Colorectal cancer (CRC) is a high-indence malignance of the digestive system with a high mortality rate in the world. The results are desired to provide an important theoretical basis for discovering new therapeutic targets for CRC. The expression of human endogenous retrovirus-H-long terminal repeat association protein 2 (HHLA2) in human CRC was detected to explore its correlationship with clinicopathological features and prognosis of patients and its potential in treating CRC. Western blot was employed to detect HHLA2 expression in fresh tissues obtained from 6 CRC patients' excisions, including cancer, paracancer, and normal issues. Immunohistochemical staining was employed to determine HHLA2 expression in paraffin-embedded specimens of 139 patients with colorectal cancer, and its relationship with the clinicopathological profiles and survival was analyzed. Small interfering RNA (siRNA) targeting HHLA2 was used to transfect CRC cells to silent HHLA2. MTT, plate colony formation, cell scratch, and Transwell assay were conducted to observe the proliferation, migration, and invasion of CRC cells. HHLA2 protein was expressed in human colorectal cancer tissues, paracancer tissues and normal tissues, which was significantly upregulated in cancer tissues (P<0.01). HHLA2 expression level in CRC tissues showed a close correlationship with the invasion depth of the tumor (P=0.000), metastasis of regional lymph nodes (P=0.018), clinical stage (P=0.010), and patient survival (P=0.011). Correlation with gender (P=0.873), age (P=0.864), location of the tumor (P=0.768), degree of tumor differentiation (P=0.569) and distant metastasis (P=0.494) exhibited no significance. The survival time of CRC patients with high and low HHLA2 expression groups was 43.231 months and 55.649 months, respectively, with a statistical difference between the two groups (P=0.001). Silencing HHLA2 inhibited proliferation, migration and invasion of CRC cells significantly. HHLA2 is overexpressed in CRC tissues which is associated with poor prognosis of patients. HHLA2 might be recognized as a new candidate for adjuvant diagnosis and prognosis of CRC, as well as a promised new target for immunotherapy of CRC.

IL-33/ST2 Signaling and its Correlation with Macrophage Heterogeneity and Clinicopathologic Features in Human Intrahepatic Cholangiocarcinoma.

IL-33/ST2 signaling plays crucial roles in the development and progression of various human malignancies. However, its significance in intrahepatic cholangiocarcinoma (ICC) still remains unclear. This study aimed to investigate the expression of IL-33/ST2 signaling and its correlations with macrophage heterogeneity and ICC patients' clinicopathologic features. The expression of different phenotype macrophage markers and IL-33/ST2 signalingrelated markers was detected. The correlation between L-33/ST2 signaling and different phenotype macrophage markers as well as ICC patients' clinicopathologic data was evaluated. Massive heterogeneous cancer cells and PAS-positive cells were observed in tumor tissues. CD68-positive cells accumulated in tumor tissues and expression of both M1 phenotype markers and M2 phenotype macrophage markers was higher in tumor samples than para-carcinoma samples. However, M2 phenotype macrophages represented the dominant macrophage population in ICC tissues. Plasma levels of IL-33, ST2, and MIF were evidently enhanced in ICC patients compared to healthy controls. IL-33/ST2 signaling-related markers exhibited a massive increase in tumor samples than para-carcinoma samples. IL-33 and ST2 expression in ICC tissues was positively associated with M1 and M2 phenotype macrophages. Plasma levels of IL-33, ST2, and MIF were correlated with the diameter of tumor lesions, lymph node metastasis, TNM stage, and tumor differentiation degree. Multivariate analysis demonstrated IL-33 expression to exhibit a correlation with the diameter of tumor lesions, lymph node metastasis, and TNM stage. Additionally, there was a relationship observed between ST2, MIF expression, and diameter of tumor lesions plus TNM stage. IL-33/ST2 signaling exhibited a positive relationship with macrophage heterogeneity in ICC tissues, and upregulated levels of IL-33, ST2, and MIF were associated with aggressive clinicopathologic characteristics. These findings may provide promising diagnostic biomarkers and potential therapeutic strategies for ICC patients targeting IL-33/ST2 signaling.

Advisory board resolution: The role of the adjuvant atezolizumab plus bevacizumab in patients with hepatocellular carcinoma at high risk of recurrence following surgical resection or ablation

MEETING DATE: July 7, 2023ITEMS ON THE AGENDA:1. The role of the adjuvant atezolizumab plus bevacizumab in patients with hepatocellular carcinoma (HCC) at high risk of recurrence following surgical resection or ablation. Profile of the patient who will benefit the most from this therapy.2. To evaluate the prospects for therapeutic options for patients with early HCC in Russia.Liver cancer remains a public health concern globally, with an increasing trend in the number of incident cases worldwide. Early, precise diagnosis and timely treatment contribute to the improvement in overall and relapse-free survival. It is important that the entire arsenal of local treatments (resection, ablation and liver transplantation) can be applied in cases when HCC is detected at a very early and early stage of the disease. Tumour recurrence after surgical treatment or ablation is a complex and underexplored problem in the treatment of patients with HCC. Many factors that can predict the risk of relapse after surgical treatment have been described: tumour size &gt;5 cm, &gt;3 foci, micro- or macrovascular (Vp1-2) invasion, poor degree of tumour differentiation (G3-4). Our advisory board tried to identify the most important risk factors for early relapse, and to determine the role and impact of the results of the first positive clinical trial focused on the issue of early HCC, IMbrave050: a phase 3 trial of adjuvant atezolizumab + bevacizumab vs active surveillance in patients with HCC at high risk of disease recurrence following resection or ablatio.

The law of paired cases on the example of adenocystic cancer of salivary glands tissue with multicentric growth of different locations

Adenoid cystic cancer of the salivary glands is characterized by recurrent and/or metastatic course. Compared with other histological types of salivary gland cancer, it usually has a more latent clinical course with a low incidence of spread to regional lymph nodes. However, after removal of the primary tumor, local and distant relapses are quite common. In addition, the presence of prognostic factors such as metastases in the lymph nodes of the neck, low degree of tumor differentiation, perineural and lymphovascular invasion contributes to an increase in the frequency of distant metastasis with a poor prognosis.&#x0D; Cases of atypical arrangement of salivary gland tissues with extranodal heterotopia are rare. In the head and neck region, different localizations of heterotopia of salivary gland tissues have been described, but the pterygopalatine fossa was not mentioned in the available sources. The difficulty of histological diagnosis when verifying heterotopia of the salivary glands may be due to the phenomena of chronic inflammation, lymphoid infiltration, tissue fibromatosis and the development of metaplasia. The rare occurrence of heterotopia of the salivary glands, the difficulties of its diagnosis and the lack of a unified approach to surgical treatment require consideration of each individually identified case.&#x0D; The law of paired cases (also known as the law of series) is implemented in the interpretation of the presented clinical cases, when the identification of individual extraorgan foci of adenoid cystic cancer of the pterygopalatine space may be associated with a rare extranodal heterotopia of salivary gland tissue. The primary multiplicity of malignant lesions of the major salivary glands and heterotopia of salivary gland tissue can be both synchronous and metachronous. Adenoid cystic cancer of the pterygomaxillary fossa, as a component of multicentric growth of various localizations, clinically confirmed the recurrent nature of the course, the tendency to distant metastasis and generalization of the malignant process.

Clinical significance of survivin mRNA expression (&lt;i&gt;BIRC5&lt;/i&gt;) in colorectal cancer

Aim. To evaluate the clinical significance of survivin (BIRC5) mRnA expression in circulating tumor cells (CTCs) and tumor material from colorectal cancer (CRC).Materials and methods. The study was organized according to the principle of a continuous prospective non-randomized study. The expression of survivin (BIRC5) mRnA in CTCs and tumor material was determined using RT-pCR.Results. The study included 130 patients (study group – 109 patients with colorectal cancer and observation group – 21 patients with colon adenomas). All patients underwent complete tumor removal (radical surgery – 93.6 %), cytoreductive – 6.4 %).A high level of survivin (BIRC5) mRnA expression was detected in colorectal adenocarcinoma in comparison with adenomas (pMann–whitney &lt; 0.001) M ± SD (1.678 ± 2.45 and 0.023 ± 0.07). In the study and observation group, the expression of survivin mRnA (BIRC5) in CTCs both before surgery M ± SD (1.175 ± 1.33 and 0.052 ± 0.11) and after 3 months M ± SD (1.015 ± 0.93 and 0.018 ± 0.002) was significantly different (pMann–whitney &lt;0.001).During adjuvant chemotherapy, a decrease in the level of survivin expression in CTCs was observed (p 9 months after surgery, CTCs remain in the bloodstream even despite adjuvant chemotherapy (p = 0.015 and p = 0.012). Overexpression of survivin in CTCs before surgery correlates with damage to regional lymph nodes (p = 0.03, r = 0.21), stage of the tumor process (p = 0.01, r = 0.25), degree of tumor differentiation (p = 0.03, r = 0.21). Overexpression of survivin in CTCs 9 months after surgery significantly affects relapse-free survival HR (95 % CI HR) = 3.1 (95 % CI 1.56–6,08, p = 0.0012) and overall survival of patients HR (95 % CI HR) =6.8 (95 % CI 2.65–17.33, p = 0.0001).Conclusions. Overexpression of survivin mRnA in colorectal cancer is a negative prognosis factor for the disease and directly depends on the tumor involvement of regional lymph nodes, the stage of the disease, degree of tumor differentiation, promoting the development of disease relapse, and can be used to diagnose minimal residual disease (MRD) and assess the prognosis of overall patient survival.