Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study.

BACKGROUND: Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. METHODS: In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. RESULTS: The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). CONCLUSIONS: This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Boosting Photothermocatalytic Oxidation of Toluene Over Pt/N-TiO2: The Gear Effect of Light and Heat.

Photothermal catalysis is extremely promising for the removal of various indoor pollutants owing to its photothermal synergistic effect, while the low light utilization efficiency and unclear catalytic synergistic mechanism hinder its practical applications. Here, nitrogen atoms are introduced, and Pt nanoparticles are loaded on TiO2 to construct Pt/N-TiO2-H2, which exhibits 3.5-fold higher toluene conversion rate than the pure TiO2. Compared to both photocatalytic and thermocatalytic processes, Pt/N-TiO2-H2 exhibited remarkable performance and stability in the photothermocatalytic oxidation of toluene, achieving 98.4% conversion and 98.3% CO2 yield under a light intensity of 260 mW cm-2. Furthermore, Pt/N-TiO2-H2 demonstrated potential practical applicability in the photothermocatalytic elimination of various indoor volatile organic compounds. The synergistic effect occurs as thermocatalysis accelerates the accumulation of carboxylate species and the degradation of aldehyde species, while photocatalysis promotes the generation of aldehyde species and the consumption of carboxylate species. This ultimately enhances the photothermocatalytic process. The photothermal synergistic effect involves the specific conversion of intermediates through the interplay of light and heat, providing novel insights for the design of photothermocatalytic materials and the understanding of photothermal mechanisms.

Analysis of eye movements of workers in safe and unsafe behaviors using a video-based method.

Analyzing eye movements of workers in safe and unsafe behaviors can reduce accidents. With a video-based method, the angular velocity of gaze direction (AVGD) represents micro-movements in gaze and angular velocity in saccade is used to analyze eye movements. A similar behavior simulation experiment is designed to collect operation videos, and an eye movement information extraction and processing framework is constructed to quantify and analyze eye movements. The results show that: the root mean square and movement frequency of AVGD can be used to recognize unsafe behavior; in operations with attention target fixation, compared with safe behavior, workers in unsafe behavior have higher angular velocity, movement frequency and turn frequency of eye movements; and in operations with attention target change, eye movement rules of workers in safe and unsafe behaviors depend on operation types. The results can provide features for unsafe behavior recognition and theoretical bases for safety training.

FOXP1 and FOXO3a Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas.

The pathologic characteristics of squamous cell/adenosquamous carcinomas (SC/ASC) have not been well clarified. As a rare subtype of gallbladder cancer (GBC), no biological markers for diagnosis and prognosis are available. This research evaluated the expression of FOXP1 and FOXO3a in 69 SC/ASC, and 146 adenocarcinoma (AC) samples were analyzed via immunohistochemistry. SC/ASCs were associated with higher rates of lymph node metastasis, invasion, and patients older than 45 years comparing to ACs. FOXP1 and FOXO3a positivity rates were significantly lower in SC/ASC and AC samples from patients with large tumor size, a high TNM stage, lymph node metastasis, invasion, and no history of tumor resection (biopsy only). Positive FOXP1 expression levels were significantly decreased in cases of poorly differentiated AC. The univariate Kaplan-Meier analysis revealed that negative FOXP1 and FOXO3a expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, invasion, and an inability to undergo curative resection were all closely associated with decreased overall survival in SC/ASC and AC patients. The multivariate cox regression analysis showed that negative FOXP1 and FOXO3a expression levels were independent predictors of poor prognosis in SC/ASC and AC patients. Our results indicate that negative FOXP1 and FOXO3a expression are closely associated with the pathogenesis, clinicopathologic properties, and prognosis of GBC patients. FOXP1 and FOXO3a may thus be biomarkers of GBC carcinogenesis, progression, and prognosis.

The expression of Aquaporin-1 and Aquaporin-3 in extrahepatic cholangiocarcinoma and their clinicopathological significance.

BACKGROUND: The aim of the study was to evaluate the expression and clinicopathological significance of Aquaporin-1 (AQP1) and Aquaporin-3 (AQP3) in extrahepatic cholangiocarcinoma (EHCC). METHODS: Immunostaining of AQP1 and AQP3 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. RESULTS: The expression of AQP1 and AQP3 protein were significantly higher in EHCC tumor tissues (P < 0.05 or P < 0.01). Adenoma and paracancerous tissues with positive AQP1 and/or AQP3 protein expression exhibited atypical hyperplasia. AQP1 expression was positive correlated with AQP3 expression in EHCC (P < 0.01). TNM I + II stage and radical surgery, the positive expression of AQP1 and AQP3 In patients with well-differentiation, no invasion, no lymph metastasis, is lower (P < 0.05 or P < 0.01). Average overall survival time of those with positive expression of AQP1 and AQP3 was significant shorter (P < 0.01). Both AQP1 and AQP3 positive expressions were proved to be an independent prognostic factors in EHCC by cox multivariate analysis. The AUC calculated for AQP1 was 0.769 (95% confidence interval [CI]: 0.618-0.920), and that for AQP3 was 0.758 (95%CI: 0.605-0.911, while that for AQP1 and AQP3 was 0.825 (95%CI: 0.658-0.991). CONCLUSIONS: Positive expression of AQP1 and AQP3 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviors, and dismal prognoses in EHCC.

Deep Learning Methods for Lung Cancer Segmentation in Whole-Slide Histopathology Images-The ACDC@LungHP Challenge 2019.

Accurate segmentation of lung cancer in pathology slides is a critical step in improving patient care. We proposed the ACDC@LungHP (Automatic Cancer Detection and Classification in Whole-slide Lung Histopathology) challenge for evaluating different computer-aided diagnosis (CADs) methods on the automatic diagnosis of lung cancer. The ACDC@LungHP 2019 focused on segmentation (pixel-wise detection) of cancer tissue in whole slide imaging (WSI), using an annotated dataset of 150 training images and 50 test images from 200 patients. This paper reviews this challenge and summarizes the top 10 submitted methods for lung cancer segmentation. All methods were evaluated using metrics using the precision, accuracy, sensitivity, specificity, and DICE coefficient (DC). The DC ranged from 0.7354 ±0.1149 to 0.8372 ±0.0858. The DC of the best method was close to the inter-observer agreement (0.8398 ±0.0890). All methods were based on deep learning and categorized into two groups: multi-model method and single model method. In general, multi-model methods were significantly better (p 0.01) than single model methods, with mean DC of 0.7966 and 0.7544, respectively. Deep learning based methods could potentially help pathologists find suspicious regions for further analysis of lung cancer in WSI.

BIRC7 and STC2 Expression Are Associated With Tumorigenesis and Poor Outcome in Extrahepatic Cholangiocarcinoma.

BACKGROUND: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for the insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC. METHODS: Immunohistochemical staining technique using the EnVision antibody complex was performed on the samples obtained from 100 EHCC, 30 peritumoral extrahepatic biliary tract (EHBT), 10 EHBT adenomas and 15 normal EHBT tissues. RESULTS: The positive rates of BIRC7 and STC2 expression in tissues obtained from peritumoral EHBT, EHBT adenomas and normal EHBT were significantly lower than those in EHCC tissues. BIRC7 and STC2 proteins were expressed at significantly higher levels in patients with lymph node metastasis, invasion of adjacent tissues, and higher TNM stage (III and/or IV) and unable to undergo resection (biopsy only). Kaplan-Meier survival curves indicated that significantly decreased overall survival rate in patients with positive-BIRC7 or positive-STC2 expression compared with patients of negative-BIRC7 or negative-STC2 expression, respectively. Cox-proportional regression analysis demonstrated that positive-BIRC7 and positive-STC2 expression, along with poor differentiation of EHCC, tumor size >3 cm, lymph node metastasis, invasion of adjacent tissues and unable to undergo resection are independent prognostic factors of EHCC patients. CONCLUSIONS: The levels of BIRC7 and STC2 expression were correlated with clinicopathological characteristics of EHCC, and positive expression of BIRC7 and STC2 are associated with progression and poor clinical outcomes of EHCC. BIRC7 and STC2 might be a potential biomarker for EHCC in clinic.

Increased expression of cystathionine beta-synthase and chemokine ligand 21 is closely associated with poor prognosis in extrahepatic cholangiocarcinoma.

The expression of Cystathionine beta-synthase (CBS) and Chemokine ligand 21 (CCL21) is associated with the tumorigenesis and progression of a variety of tumors, but whether alterations in their expression levels correlates with the carcinogenesis and progression of EHCC is still unknown. This study investigated the clinicopathological significance of CBS and CCL21 expression in EHCC.We investigated the correlations between the expression of CBS and CCL21 and clinicopathological characteristics in EHCC using EnVision immunohistochemistry.The expression of CBS and CCL21 was significantly higher in EHCC tumors than in nontumor tissues (P < .05 and P < .01). EHCC patients with CBS and CCL21 expression combined with lymph node metastasis, tumor cell invasion, and TNM III/IV stage had more severe conditions than those with no lymph node metastasis, distant invasion and TNM I/II stage (P < .01). Kaplan-Meier survival analysis showed that the overall survival rates for EHCC patients with negative CBS or CCL21 reaction were significantly higher than those for patients with positive CBS or CCL21 reaction((P < .01). CBS or CCL21 expression was revealed as an independent poor prognostic factor for EHCC patients by Cox multivariate analysis.The present study indicates that CBS and CCL21 expression is closely associated with the pathogenesis of clinical, pathological and biological behaviors and poor prognosis in EHCC.

Comparison of ADAM19 and CUEDC2 expression in EHCC and their clinicopathological significance.

Background: To evaluate the expression and clinicopathological significance of a disintegrin and metalloproteinases 19 (ADAM19) CUE domain containing protein 2 (CUEDC2) in extrahepatic cholangiocarcinoma (EHCC). Materials & methods: Immunostaining of ADAM19 and CUEDC2 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. Result: The expression of ADAM19 and CUEDC2 were significantly higher in EHCC (p < 0.05). ADAM19 expression was positive correlated with CUEDC2 expression in EHCC (p < 0.05). The overall survival time of those with positive expression of ADAM19 and CUEDC2 was lower (p < 0.001). Both positive expression of ADAM19 and CUEDC2 were independent prognostic factors in EHCC. Conclusion: ADAM19 and CUEDC2 have a positive correlation to the pathogenesis and dismal prognosis in EHCC.

Prognostic and Clinicopathological Significance of X-Box-Binding Protein 1 and N-Acetyltransferase 1 in Gallbladder Cancer.

Background: X-box-binding protein 1 (XBP1) and N-acetyltransferase 1 (NAT1) are involved in oncogenesis and progression of many human cancer types. However, the roles of XBP1 and NAT1 in gallbladder cancer (GBC) are never reported. Methods: We examined XBP1 and NAT1 expression in GBC and matched adjacent non-tumor tissues via Western blotting. Then, we assayed XBP1 and NAT1 expression in 215 GBCs, including 69 squamous cell/adenosquamous carcinomas (SC/ASCs) and 146 adenocarcinomas (ACs) with immunohistochemistry. Their prognostic and clinicopathological significance was further evaluated using the χ2 test or Fisher's exact test, Kaplan-Meier univariate survival analysis, and log-rank tests. Results: XBP1 expression was upregulated, and NAT1 expression was downregulated in GBC. Immunohistochemical results showed that XBP1 expression was negatively associated with NAT1 expression in GBC, including SC/ASC and AC. The rate of patients with an age of more than 45 years, positivity of lymph node metastasis, and invasion were significantly higher in SC/ASC than those in AC (all P < 0.05). The percentage of XBP1-positive and NAT1-negative expression was significantly higher in the cases with poor differentiation, advanced tumor, nodes, and metastases (TNM) stage, lymph node metastasis, invasion, and only receiving biopsy in GBC, SC/ASC, and AC (all P < 0.05). XBP1-positive and NAT1-negative expression was positively related to larger tumor size (>3 cm) in GBC and AC. There was a negative association between XBP1 and NAT1 expression in GBC, SC/ASC, and AC (all P < 0.05). Positive XBP1 and negative NAT1 expression was closely associated with decreased overall survival in GBC, SC/ASC, and AC patients (all P < 0.05). The multivariate Cox regression analysis showed that positive XBP1 or negative NAT1 expression was an independent factor for poor prognosis in gallbladder SC/ASC and AC patients. Conclusions: This study indicates that positive XBP1 and negative NAT1 expression are closely associated with the clinicopathological and biological behaviors and poor prognosis in GBC.

Negative Expression of DSG1 and DSG2, as Prognostic Biomarkers, Impacts on the Overall Survival in Patients with Extrahepatic Cholangiocarcinoma.

AIMS: To evaluate the expression of DSG1 and DSG2 and investigate their clinicopathological significance in EHCC. METHOD: The protein expression of DSG1 and DSG2 was measured by EnVision immunohistochemistry in 15 normal biliary tract tissues, 10 biliary tract adenoma tissues, 30 peritumoral tissues, and 100 EHCC tumour tissues. RESULT: The expression of the DSG1 and DSG2 proteins was significantly lower in EHCC tumour tissues than in normal biliary tract tissues, biliary tract adenoma, and peritumoral tissues (P < 0.05). Adenoma and peritumoral tissues with negative DSG1 and/or DSG2 protein expression exhibited atypical hyperplasia. DSG1 expression was positively correlated with DSG2 expression in EHCC (P < 0.01). In patients with good differentiation, no invasion, no lymph metastasis, TNM I + II stage, and radical surgery, the positive expression of DSG1 and DSG2 proteins was higher (P < 0.05). In comparison to patients with negative DSG1 and/or DSG2 expression, the average overall survival time of those with positive expression was significantly longer (P = 0.000). Cox multivariate analysis revealed that negative DSG1 and DSG2 expressions were independent of poor prognosis factors in EHCC patients. The AUC calculated for DSG1 was 0.681 (95% confidence interval: 0.594-0.768) and that for DSG2 was 0.645 (95% confidence interval: 0.555-0.734), while that for DSG1 and DSG2 was 0.772 (95% confidence interval: 0.609-0.936). CONCLUSIONS: Negative protein expression of DSG1 and DSG2 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviours, and dismal prognosis in EHCC.

XRCC1 Is a Promising Predictive Biomarker and Facilitates Chemo-Resistance in Gallbladder Cancer.

Gallbladder cancer is a relatively uncommon human malignant tumor with an extremely poor prognosis. Currently, no biomarkers can accurately diagnose gallbladder cancer and predict patients' prognosis. XRCC1 is involved in tumorigenesis, progression, and chemo-resistance of several human cancers, but the role of XRCC1 in gallbladder cancer is never reported. In this study, we investigated the expression of XRCC1 and its clinicopathological and prognostic significance in gallbladder cancer, and explored the biological role of XRCC1 in gallbladder cancer cells. We found that XRCC1 was significantly up-regulated in gallbladder cancer in protein and mRNA levels. Positive XRCC1 expression was correlated with aggressive clinicopathological features and was an independent poor prognostic factor in gallbladder cancer. The ROC curves suggested that XRCC1 expression had potential clinicopathological diagnostic value in gallbladder cancer. In vitro, XRCC1 was overexpression in CD133+GBC-SD cells compared to GBC-SD cells. In functional experiment, XRCC1 knockdown had a non-significant impact on proliferation, migration, invasion, and apoptosis of CD133+GBC-SD cells. But, XRCC1 knockdown could significantly improve the sensitivity of CD133+GBC-SD cells to 5-Fluorouracil via promoting cell necrosis and apoptosis. Thus, this study indicates that XRCC1 may be a promising predictive biomarker of gallbladder cancer and a potential therapeutic target for gallbladder cancer.

ACO2 and ANPEP as novel prognostic markers for gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas.

BACKGROUND: Squamous cell/adenosquamous carcinoma (SC/ASC) is a rarely identified form of gallbladder cancer with poorly understood clinical features. As such, there is an urgent need to identify novel prognostic biomarkers for such gallbladder SC/ASC cases, and for gallbladder adenocarcinomas (ACs). METHODS: The levels of ACO2 and ANPEP proteins were assessed via an EnVision-based immunohistochemical approach using 46 SC/ASC and 80 AC patient samples. RESULTS: There was a marked reduction in levels of ACO2 and ANPEP in gallbladder AC relative to normal adjacent tissue or benign gallbladder lesions. The was a significant correlation between lack of ACO2 and ANPEP and larger tumors, higher tumor-node-metastasis (TNM) staging, invasion, metastasis to regional lymph nodes, and ineligibility for surgical resection in both SC/ASC and AC tumor samples. Kaplan-Meier survival analyses further confirmed a relationship between ACO2 and ANPEP negativity and decreased overall survival in patients with these diseases (p < 0.05 or p < 0.01), and a multivariate regression analysis further established that ACO2 negativity and ANPEP negativity were independently predictive of poor SC/ASC and AC patient outcomes. CONCLUSIONS: ACO2 and ANPEP may have key physiological relevance in cancers of the gallbladder and thus warrant investigation as prognostic biomarkers.

Prognostic and Clinicopathological Significance of EphB3 and Dysadherin Expression in Extrahepatic Cholangiocarcinoma.

AIM: EphB3 and dysadherin are involved in tumorigenesis and progression of many neoplasms. However, the roles of EphB3 and dysadherin in extrahepatic cholangiocarcinoma (ECC) remain to be revealed. In this study, we aimed to evaluate the expression of EphB3 and dysadherin, and investigate their clinicopathological significance in ECC. METHODS: We examined EphB3 and dysadherin expression in 100 ECC, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues using EnVision immunohistochemistry. The relationship between EphB3 or dysadherin expression and clinicopathological features was evaluated using the χ 2 test or Fisher's exact test. The overall survival of ECC patients was analyzed using Kaplan-Meier univariate survival analysis and Log rank tests. RESULTS: We found that EphB3 expression was significantly down-regulated and dysadherin expression was significantly up-regulated in ECC tissues compared with normal tissues (P < 0.01). EphB3 expression was negatively correlated with dysadherin expression in ECC (P < 0.01). The positive rate of EphB3 expression and negative rate of dysadherin expression was significantly higher in patients with well-differentiated type, no lymph node metastasis, no surrounding tissues and organs invasion, early TNM stages (I + II) and radical resection (P < 0.01). The survival of ECC patients with positive EphB3 or negative dysadherin expression was significantly longer than patients with negative EphB3 or positive dysadherin expression (P < 0.01). Cox multivariate analysis demonstrated that negative EphB3 or positive dysadherin expression were independent poor prognostic factors in ECC patients. The ROC curves suggested that EphB3 and dysadherin combined diagnostic efficacy (AUC=0.688, 95%CI: 0.603-0.772) was significantly higher EphB3 diagnostic efficacy (AUC=0.654, 95%CI: 0.564-0.743) or dysadherin diagnostic efficacy (AUC=0.648, 95%CI: 0.558-0.737) alone. CONCLUSION: EphB3 and dysadherin are involved in the carcinogenesis and progression of ECC, and ECC patients with negative EphB3 or positive dysadherin expression have a poor prognosis.

Clinical Significance of CBS and CCL21 in Gallbladder Adenocarcinomas and Squamous Cell/Adenosquamous Carcinomas.

Gallbladder cancer (GBC) is a rare disease with high mortality. However, no biomarkers for the carcinogenesis, progression, prognosis, and early diagnosis are clinically available. This study investigated the expressions of cystathionine-ß-synthase (CBS) and C-C chemokine receptor 7 (CCR7) protein and their clinical and pathologic significances in gallbladder squamous cell/adenosquamous carcinomas (SC/ASC) and adenocarcinomas (AC). CBS and chemokine ligand 21 (CCL21) expression was measured using immunohistochemistry in 69 SC/ASCs and 146 ACs. A significantly high percentage of patients with an age above 45 years, lymph node metastasis, and invasion was observed in the SCs/ASCs compared with ACs (P<0.05). Both AC and SC/ASC patients with positive CBS and CCL21 expression exhibited a high tumor-lymph node-metastasis stage, lymph node metastasis, and invasion compared with patients with negative CBS and CCL21 expression (P<0.05 or P<0.01). SC/ASC patients with positive CBS expression was prone to have a larger tumor size than those with negative expression (P<0.05). Positive CBS and CCL21 expression correlated with poor differentiation and larger tumor size in AC patients. Positive CBS and CCL21 are closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.01) and were independent factors for a poor-prognosis. Both CBS and CCL21 showed a good overall diagnostic performance for SC/ASC (AUC=0.742 and AUC=0.764, respectively) and AC (AUC=0.734 and AUC=0.718, respectively). In conclusion, positive CBS and CCL21 expression are closely associated with the clinical severity and poor prognosis in GBC, and can be a marker for the diagnosis of AC and SC/ASC type of GBC.

Prognostic and clinicopathological significance of Hapto and Gremlin1 expression in extrahepatic cholangiocarcinoma.

Background: Some studies have demonstrated that Hapto and Gremlin1 play an important biological role in many neoplasms. However, the role of Hapto and Gremlin1 in extrahepatic cholangiocarcinoma (ECC) remains to be revealed. Thus, this study investigated the prognostic and clinicopathological significance of Hapto and Gremlin1 expression in ECC. Methods: We examined Hapto and Gremlin1 expression in 100 ECC, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues using EnVision immunohistochemistry. The relationship between Hapto and Gremlin 1 expression and clinicopathological parameters was evaluated using the χ2 test or Fisher's exact test. The overall survival of patients was analyzed using Kaplan-Meier univariate survival analysis and log-rank tests. Results: Hapto and Gremlin1 proteins were overexpressed in ECC compared to peritumoral tissues, adenoma, and normal biliary tract (P<0.05 or P<0.01). The positive rate of Hapto and Gremlin1 expression was significantly higher in cases with poor differentiation, lymph node metastasis, invasion of surrounding tissues and organs, a tumor-node-metastasis (TNM) stage of III or IV and no resection. Kaplan-Meier survival analysis showed that ECC patients with positive Hapto and/or Gremlin1 expression survived significantly shorter than patients with negative Hapto and/or Gremlin1 expression. Cox multivariate analysis revealed that positive Hapto and Gremlin1 expression were independent poor prognostic factors in ECC patients. Conclusion: The present study indicated that positive Hapto and/or Gremlin1 expression are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in ECC.

The expressions of HMGA2 and Thy1 in extrahepatic cholangiocarcinoma and their clinicopathological significances.

AIMS: Extrahepatic cholangiocarcinoma is a malignant tumor and poor prognosis with intrinsic resistance to cytotoxic agents. The molecular mechanism associated with high malignancy and resistance to chemotherapy and radiotherapy has not been fully elucidated. This study aims to investigate the clinicopathological significances of HMGA2 and Thy1 expression in extrahepatic cholangiocarcinoma. METHODS: The expressions of HMGA2 and Thy1 in 100 extrahepatic cholangiocarcinoma, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues were assayed using EnVision immunohistochemistry. RESULTS: The HMGA2 and Thy1 proteins were overexpression in extrahepatic cholangiocarcinoma compared to peritumoral tissues, adenoma, and normal biliary tract tissues (P < 0.05 or P < 0.01). Adenoma and pericancerous tissues with positive HMGA2 or/and Thy1 protein expression exhibited atypical hyperplasia. The positive correlation was found between the expression of HMGA2 and Thy1 in extrahepatic cholangiocarcinoma (P < 0.01). The positive rates of HMGA2 and Thy1 expression were significantly higher in cases with poor differentiation, lymph node metastasis, invasion, and TNM stage III or IV and no resection (biopsy only) (P < 0.05 or P < 0.01). Kaplan-Meier survival analysis showed that the survival of extrahepatic cholangiocarcinoma patients with positive HMGA2 and/or Thy1 expression is significantly shorter than patients with negative HMGA2 and/or Thy1 expression (P = 0.000). Cox multivariate analysis revealed that positive HMGA2 and/or Thy1 expressions were independently poor prognosis factors in extrahepatic cholangiocarcinoma patients. We calculated the AUC for HMGA2 (AUC = 0.610, 95%CI: 0.519-0.702), or Thy1 (AUC = 0.675, 95%CI: 0.588-0.762), respectively. CONCLUSIONS: The present study indicated that positive HMGA2 and Thy1 expression are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in patients with extrahepatic cholangiocarcinoma.

Enormous primary renal diffuse large B-cell lymphoma: A case report and literature review.

INTRODUCTION: Primary renal lymphoma is a rare malignant lymphoma that is difficult to differentiate from renal cell carcinoma. Positron emission tomography/computed tomography and image-guided percutaneous biopsy are valuable tools for diagnosis. CASE REPORT: A 64-year-old woman presented with a 2-year history of repeated right waist pain and a 1-month history of nausea, vomiting, and frequent and urgent urination. A computed tomography scan showed a huge mass that was initially considered to be renal cell carcinoma at the upper pole of the right kidney. The mass had invaded the renal pelvis, narrowed the right renal artery, and constricted the inferior vena cava and liver. Postoperative examination of the tumor confirmed lymphoma. We herein present this case and its multidisciplinary team management. CONCLUSION: Multidisciplinary team management is efficient for preoperative assessment and surgery in difficult and high-risk cases. Based on our literature review, we suggest biopsy before chemotherapy whenever possible. Chemotherapy can be implemented after surgery for better survival outcomes.

Expression of FOXP1 and FOXO3a in extrahepatic cholangiocarcinoma and the implications in clinicopathological significance and prognosis.

Aims: Extrahepatic cholangiocarcinoma (EHCC) is a highly malignant tumor with poor prognosis and intrinsic resistance to cytotoxic agents. The molecular mechanisms associated with high malignancy and resistance to chemotherapy and radiotherapy have not been fully elucidated. This study investigated the clinicopathological significances of FOXP1 and FOXO3a expression in EHCC. Methods: We assayed FOXP1 and FOXO3a expressions in 100 EHCC, 30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues using EnVision immunohistochemistry. Results: The positive rates of FOXP1 and FOXO3a proteins were significantly lower in EHCC tumors than in peritumoral tissues, adenoma, and normal bile tract tissues (P<0.05 or P<0.01). Adenoma and pericancerous tissues with negative FOXP1 and/or FOXO3a protein expressions exhibited atypical hyperplasia. The positive correlation was established between the expression of FOXP1 and FOXO3a in EHCC (P<0.01). The positive rates of FOXP1 and FOXO3a expression were significantly higher in cases with well differentiation, no metastasis in lymph node, no invasion to surrounding tissues and organs, TNM I + II stage and radical resection (p<0.05 or p<0.01). Kaplan-Meier survival analysis showed that EHCC patients with positive FOXP1 and FOXO3a expression survived significantly higher than patients with negative FOXP1 and FOXO3a expression, respectively (P<0.001). Cox multivariate analysis revealed that negative FOXP1 or FOXO3a expressions were independent poor prognostic factors in EHCC patients. The AUCs for FOXP1 and FOXO3a were 0.676 (95% CI: 0.589-0.763, P＜0.001) and 0.652 (95% CI: 0.563-741, P=0.002), respectively. Conclusion: The present study indicates that negative FOXP1 and FOXO3a expressions are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in EHCC.

DDR2 and IFITM1 Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas.

This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2 was significantly higher in SC/ASC patients with large tumor sizes than patients with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1 expressions was significantly higher in AC patients with high TNM stages that didn't receive resection surgery compared to patients with low TNM stages that did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1 was significantly higher in AC patients with lymph node metastasis and invasion than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and IFITM1 expression was closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC.