YAP targetome reveals activation of SPEM in gastric pre-neoplastic progression and regeneration.

Peptic ulcer disease caused by environmental factors increases the risk of developing gastric cancer (GC), one of the most common and deadly cancers in the world. However, the mechanisms underlying this association remain unclear. A major type of GC uniquely undergoes spasmolytic polypeptide-expressing metaplasia (SPEM) followed by intestinal metaplasia. Notably, intestinal-type GC patients with high levels of YAP signaling exhibit a lower survival rate and poor prognosis. YAP overexpression in gastric cells induces atrophy, metaplasia, and hyperproliferation, while its deletion in a Notch-activated gastric adenoma model suppresses them. By defining the YAP targetome genome-wide, we demonstrate that YAP binds to active chromatin elements of SPEM-related genes, which correlates with the activation of their expression in both metaplasia and ulcers. Single-cell analysis combined with our YAP signature reveals that YAP signaling is activated during SPEM, demonstrating YAP as a central regulator of SPEM in gastric neoplasia and regeneration.

Expression patterns of claudins in cancer.

Claudins are four-transmembrane proteins, which were found in tight junctions. They maintain cell barriers and regulate cell differentiation and proliferation. They are involved in maintaining cellular polarity and normal functions. Different claudins show different expression patterns. The expression level and localization of claudins are altered in various cancers. They promote or inhibit proliferation, invasion, and migration of cancer cells through multiple signaling pathways. Therefore, claudins may serve as diagnostic markers, novel therapeutic targets, and prognostic risk factors. The important roles of claudins in cancer aroused our great interest. In the present review, we provide a summary of insights into expression patterns of claudins in cancer, which is more comprehensive and provides new ideas for further research.

Association between metabolic syndrome and early-stage colorectal cancer.

BACKGROUND: Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC. METHODS: We conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test. RESULTS: There were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients < 50 years of age (OR 1.77; 95% CI 1.01 to 3.12), but not for women patients (OR 0.84; 95% CI 0.79 to 0.90). MetS patients were associated with a higher risk of advanced serrated lesions than that of conventional adenomas (OR 1.585; 95% CI 1.02 to 2.45), especially in patients ≥ 50 years (OR 1.78; 95% CI 1.11 to 2.85). CONCLUSIONS: Metabolic dysregulation might partly contribute to the incidence of colorectal serrated lesions. Prevention of MetS should be highly appreciated in the early diagnosis and early treatment of the colorectal cancer system, especially in patients ≥ 50 years.

Correlation of Claudin18.2 expression with clinicopathological characteristics and prognosis in gastric cancer.

OBJECTIVES: Claudin18.2 (Cldn18.2) is a tight junction protein expressed in gastric epithelial cells and is an emerging target for gastric cancer (GC). This study aimed to analyze the correlation between Cldn18.2 and clinicopathological parameters in GC patients undergoing radical surgery. METHODS AND RESULTS: This study included 426 GC patients who underwent radical gastrectomy. The expression of Cldn18.2 was analyzed by immunohistochemical staining and grading. The statistical results indicated that the expression of Cldn18.2 was correlated with T stage, TNM stage, Lauren classification, and the expression level of Mucin-2 (MUC2), Mucin-5AC (MUC5AC), Mucin-6 (MUC6), human epidermal growth factor receptor 2 (HER2), P53 and trefoil factor 2 (TFF2). In addition, through data mining of the Cancer Genome Atlas (TCGA) database, it is suggested that Cldn18.2 expression level is significantly correlated with the expression level of MUC5AC, MUC6, and TFF2. Besides, Cldn18.2 is related to tumor immune infiltration, programmed cell death protein 1 (PD 1) pathway, cell cycle and Wnt signaling pathway. CONCLUSIONS: The expression of Cldn18.2 was closely related to gastric-type GC, so gastric-type GC patients may benefit more from targeted drugs targeting Cldn18.2. In GC cells, depletion of Cldn18.2 may influence cell cycle and immune response by affecting Wnt signaling pathway and PD 1 pathway.

An adjusted Asia-Pacific colorectal screening score system to predict advanced colorectal neoplasia in asymptomatic Chinese patients.

PURPOSE: The Asia-Pacific Colorectal Screening (APCS) score and its derivatives have been used to predict advanced colorectal neoplasia (ACN). However, it remains unknown whether they apply to the current Chinese population in general clinical practice. Therefore, we aimed to update the APCS score system by applying data from two independent asymptomatic populations to predict the risk of ACN in China. METHODS: We developed an adjusted APCS (A-APCS) score by using the data of asymptomatic Chinese patients undergoing colonoscopies from January 2014 to December 2018. Furthermore, we validated this system in another cohort of 812 patients who underwent screening colonoscopy between January and December 2021. The discriminative calibration ability of the A-APCS and APCS scores was comparatively evaluated. RESULTS: Univariate and multivariate logistic regression were applied to assess the risk factors for ACN, and an adjusted scoring system of 0 to 6.5 points was schemed according to the results. Utilizing the developed score, 20.2%, 41.2%, and 38.6% of patients in the validation cohort were classified as average, moderate, and high risk, respectively. The corresponding ACN incidence rates were 1.2%, 6.0%, and 11.1%, respectively. In addition, the A-APCS score (c-statistics: 0.68 for the derivation and 0.80 for the validation cohort) showed better discriminative power than using predictors of APCS alone. CONCLUSIONS: The A-APCS score may be simple and useful in clinical applications for predicting ACN risk in China.

PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway.

Gastric cancer is a high molecular heterogeneous disease with a poor prognosis. Although gastric cancer is a hot area of medical research, the mechanism of gastric cancer occurrence and development is still unclear. New strategies for treating gastric cancer need to be further explored. Protein tyrosine phosphatases play vital roles in cancer. A growing stream of studies shows that strategies or inhibitors targeting protein tyrosine phosphatases have been developed. PTPN14 belongs to the protein tyrosine phosphatase subfamily. As an inert phosphatase, PTPN14 has very poor activity and mainly functions as a binding protein through its FERM (four-point-one, ezrin, radixin, and moesin) domain or PPxY motif. The online database indicated that PTPN14 may be a poor prognostic factor for gastric cancer. However, the function and underlying mechanism of PTPN14 in gastric cancer remain unclear. We collected gastric cancer tissues and detected the expression of PTPN14. We found that PTPN14 was elevated in gastric cancer. Further correlation analysis indicated that PTPN14 was relevant with the T stage and cTNM (clinical tumor node metastasis classification) stage. The survival curve analysis showed that gastric cancer patients with higher PTPN14 expression had a shorter survival time. In addition, we illustrated that CEBP/ß (CCAAT enhanced binding protein beta) could transcriptionally activate PTPN14 expression in gastric cancer. The highly expressed PTPN14 combined with NFkB (nuclear factor Kappa B) through its FERM domain and accelerated NFkB nucleus translocation. Then, NFkB promoted the transcription of PI3KA and initiated the PI3KA/AKT/mTOR pathway to promote gastric cancer cell proliferation, migration, and invasion. Finally, we established mice models to validate the function and the molecular mechanism of PTPN14 in gastric cancer. In summary, our results illustrated the function of PTPN14 in gastric cancer and demonstrated the potential mechanisms. Our findings provide a theoretical basis to better understand the occurrence and development of gastric cancer.

Ratiometric fluorescent detection of exosomal piRNA-823 based on Au NCs/UiO-66-NH2 and target-triggered rolling circle amplification.

piR-823 is a newly discovered colorectal cancer marker with high diagnostic efficacy. However, the current quantification methods have complicated operations and high cost, which restrict its clinical application. Herein, a metal-organic framework (MOF) with a UiO-66 prototype structure which supports gold nanoclusters (Au NCs), Au NCs/UiO-66-NH2, were prepared as a model nanobiosensing platform for ratiometric detection of exosomal piR-823. The rolling circle amplification process provides high sensitivity and the ratiometric detection process ensures good accuracy of the sensor. Such biosensor showed a wide linear range of 0.04-4 pM, and a low detection limit of 10.2 fM towards piR-823. In addition, piR-823 can be used as an effective supplement to carcinoembryonic antigen (CEA) in clinical diagnosis of colorectal cancer. This study not only provides a potentially valuable ratio fluorescence platform involving enzyme catalytic reaction, but also offers a design blueprint for further expansion of nanotechnology in the diverse biological analysis.

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer.

Recently, kinesin family member 21B (KIF21B) has been reported to be an oncogene in non-small cell lung cancer and hepatocellular carcinoma. However, the functional role of KIF21B and related molecular mechanisms in gastric cancer (GC) remain largely uncovered. In this study, online bioinformatics analysis showed that KIF21B was overexpression in GC and predicted poor prognosis. Consistently, we found that the protein expression of KIF21B was upregulated in GC tissues compared with adjacent tissues by immunohistochemistry. Knockdown of KIF21B significantly suppressed cell proliferation, migration and invasion in GC cell lines (AGS and SNU-5) using Cell counting kit­8 (CCK-8) assay, colony formation and transwell assay. KIF21B was confirmed as the target of miR-132-3p in GC cells by luciferase reporter assay. Moreover, miR-132-3p was down-regulated and KIF21B expression was upregulated in GC tissues. Overexpression of KIF21B reversed the miR-132-3p-mediated suppressive effects on GC cell proliferation, migration and invasion. Furthermore, miR-132-3p overexpression downregulated the protein levels of Wnt1, c-Myc, ß-catenin, proliferating cell nuclear antigen (PCNA) and N-cadherin, and upregulated E-cadherin expression in GC cells, which were all alleviated after KIF21B overexpression. In conclusion, our findings indicate that down-regulation of KIF21B by miR-132-3p suppresses cellular functions in GC, which might be linked to reduced Wnt/ß-catenin signaling.

Clinicopathologic features and prognosis of epithelioid glioblastoma.

OBJECTIVE: To improve the understanding of epithelioid glioblastoma (E-GBM) and provide accurate basis for clinical diagnosis, treatment, and prognosis through the analysis of clinicopathologic characteristics, immunohistochemical expression, molecular characteristics, and prognosis of E-GBM. METHODS: The clinicopathologic characteristics of 33 cases of E-GBM in our hospital from January 2015 to September 2019 were analyzed retrospectively. Kaplan Meier method was used for survival analysis. Multivariate Cox regression analysis was used to screen the independent risk factors affecting the survival time of patients. RESULTS: Among 33 patients with E-GBM, 16 were male and 17 were female. The age ranged from 9 to 67 years old, with the median age of 36 years old and the average age of 38 years old. The tumor size (calculated by the largest diameter): 1-6 cm, average size: 3.5 cm. The ratio of smoking and non-smoking is 17:16. All the tumors were located in the cerebral hemisphere, and 26 cases (78.79%) of brain MR showed that the tumors invaded the cortex (white matter). CLINICAL SYMPTOMS: asymptomatic physical examination was found in 6 cases (18.18%), 5 cases (15.15%) had epilepsy history, 2 cases (6.06%) had malignant vomiting, 3 cases (9.09%) had hypertension history, and 17 cases (51.52%) had headache and dizziness. All patients received surgery (total or partial resection). Postoperative radiotherapy was given in 7 cases (21.00%), chemotherapy (TMZ temozolomide) in 3 cases (1.00%), and combined chemoradiotherapy in 16 cases (48.40%). Immunohistochemical staining: the positive rates of CK, GFAP, IDH-1, IDH-2, HMB45, Desmin, BRAF, P53, ATRX, INI-1, S-100, Ki-67 were 20/33, 30/33, 1/33, 1/33, 0/33, 0/33, 33/33, 5/33, 30/33, 33/33, 6/33, Ki-67 of all cases were higher than 40%, among which 11 cases were higher than 60%. The detection of related genes showed that 33 cases (100%) had BRAF V600E mutation. TERT mutation was found in 18 cases (54.5%); IDH1 mutation was found in 1 case (3%); MGMT promoter methylation was found in 15 cases (45.4%); EGFR amplification and 1p/19q co-deletion were not found in any cases. CONCLUSION: E-GBM is a highly invasive and rare malignant nervous system tumor, with poor prognosis and lack of clinical specificity. Immunohistochemically, the higher expression of CK, GFAP and Ki67 proliferation index is more conducive to the diagnosis and differential diagnosis of E-GBM. Smoking, brain MR showing tumor invasion of cortex, TERT mutation, radiotherapy, and chemotherapy are independent risk factors affecting the prognosis (survival time) of patients.

High expression of carcinoembryonic antigen-associated cell adhesion molecule 1 is associated with microangiogenesis in esophageal squamous cell carcinoma.

BACKGROUND: Carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1) plays an important role in tumor progression, invasion, and metastasis by regulating angiogenesis. However, the expression of CEACAM1 in esophageal cancer tissues and its relationship with microvessel density (MVD) has not been investigated before. METHODS: MVD and the expression of CEACAM1 in 80 esophageal squamous cell carcinoma (ESCC) tissues were determined by immunohistochemistry (IHC). Statistical analyses were conducted to test the associations between CEACAM1 expression, MVD level, clinicopathologic factors, and prognosis. RESULTS: The expression level of CEACAM1 was significantly correlated with the level of MVD. Kaplan-Meier analysis showed no significant correlations between local recurrence and distant metastasis in high MVD and high CEACAM-1 expression group. Kaplan-Meier analysis also showed a poorer survival rate in patients with high MVD or high CEACAM-1. Univariate analysis showed that MVD levels, CEACAM1 expression, lymph node metastasis, and patient's age were prognostic factors for postoperative ESCC. The results of multivariate analysis indicated that the significance of the prognostic effect of CEACAM-1 expression observed by univariate analysis disappeared when analyzed together with MVD, suggesting that the prognostic impact of CEACAM1 expression was dependent on MVD level, while MVD was still a significant prognostic factor for adverse cancer-related survival (P=0.001). CONCLUSIONS: The CEACAM1 expression is a potential prognostic factor for postoperative ESCC combined with MVD level.

The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer.

The aim of this study was to investigate the expression of minichromosome maintenance complex component 7 (MCM7) in gastric mucosal lesions, further to find its potential effect as a biomarker to distinguish intraepithelial neoplasia from gastric mucosal lesions. MCM7 and Ki67 were detected in 93 cases of gastric mucosal lesions by immunohistochemistry. MCM7 and Ki67 expression in GT were lowest compared with other groups (P<0.001), meanwhile there were significant differences compared with Group IM and other groups in MCM7 and Ki67 expression (P<0.001). MCM7 and Ki67 expression in GSC were highest (P<0.05). Groups of LGN, HGN and GIC had no significant differences in MCM7 expression (P>0.05), but there was significant difference compared with Group LGN and Group GIC in Ki67 expression (P<0.05). MCM7 expression elevated with tumor grade increasing and had positive correlation with Ki67 significantly (r=0.940, P<0.001). Furthermore, in some cases, some tumor cells were immunoreactive to MCM7 but negative to Ki67. So we concluded that MCM7 is helpful for us to make differential diagnosis in pathological grade, MCM7 combination of Ki67 may serve as more sensitive proliferation markers for evaluation of gastric carcinoma and precancerous lesions.

CEACAM1 is overexpressed in oral tumors and related to tumorigenesis.

Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) is a type 1 transmembrane glycoprotein belonging to the CEA family, which has been known to exist as either soluble forms in body fluids or membrane-bound forms on the cell surface. Aberrant CEACAM1 expression is associated with tumorigenesis and has been reported in a variety of human tumors, especially malignancies. The aim of this study is to determine the expression of CEACAM1 in oral tumors, trying to study CEACAM1 different expressions as a function of histotype. CEACAM1 expression was observed by immunohistochemistry (IHC) with mouse anti-human antibody for CEACAM1. IHC was performed using avidin-biotin-diaminobenzidine staining. The results were expressed as average score ± SD (0 = negative/8 = highest) for each histotype. Oral tumors expressed more CEACAM1 than normal tissues including squamous and salivary epithelia (P < 0.05). In malignancies, the squamous cell carcinoma overexpressed CEACAM1, compared to well-differentiated squamous cell with more membranous expression; the intermediately and poorly differentiated squamous cell carcinoma showed more cytoplasmic expression (P < 0.05). In addition, the salivary tumors significantly expressed more CEACAM1 than squamous cell carcinoma (P < 0.05). So, we thought oral tumors overexpressed CEACAM1 and the cytoplasmic CEACAM1 might be involved in tumorigenesis, and also CEACAM1 might be regarded as a marker of salivary glandular tumors.

Carcinoembryonic antigen-related cell adhesion molecule 1 is expressed and as a function histotype in ovarian tumors.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma (P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern (P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis.

Minichromosome maintenance complex component 7 has an important role in the invasion of papillary urothelial neoplasia.

The aims of the present study were to investigate the expression of minichromosome maintenance complex component 7 (MCM7) and determine its association with tumor proliferation and invasion in pathological tumor (pT)a and pT1 papillary urothelial neoplasia. The MCM7, MCM3 and Ki67 proteins were detected in 154 cases of urothelial neoplasia using immunohistochemical analysis. The expression of MCM7 significantly increased (P<0.001) as the pathological stage and grade progressed between inverted papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), pTa tumor and pT1 tumor. However, no statistically significant difference in MCM7 staining was observed between low-grade pTa tumors and PUNLMP (P=0.2294). In contrast to MCM7, MCM3 was highly expressed in all stages of urothelial neoplasia, with no statistically significant differences observed between the tumor types (P=0.2993, 0.3885 and 0.8489 for pTa tumors, PUNLMP and inverted papiloma, respectively). Furthermore, MCM7 expression was elevated with increased tumor grade and was positively correlated with Ki67 expression (rs =0.9106, P<0.001). However, MCM3 expression was not correlated with MCM7 or Ki67 expression (rs =0.0734, P=0.3657 and rs =0.0638, P=0.4318, respectively). In conclusion, MCM7 overexpression may simultaneously promote tumor proliferation and invasion. Furthermore, it may be a reliable marker for the pathological differential diagnosis of pTa and pT1 papillary urothelial neoplasms; therefore, MCM7 expression may be used to predict tumor prognosis and behavior.

High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.

We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1α, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p<0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.

Frequencies of BCL2 and BCL6 translocations in representative Chinese follicular lymphoma patients: morphologic, immunohistochemical, and FISH analyses.

The most common genetic aberration in follicular lymphoma (FL) is the t(14;18)(q32;q21) translocation that juxtaposes the antiapoptotic BCL2 gene with the promoter of the immunoglobulin heavy-chain (IgH) gene, which is the molecular hallmark of FL, whereas a subset of cases harbor translocations involving the BCL6 gene locus. To date, there has been no integrated analysis based on grade, phenotype, and genotype from large numbers of FL cases in a representative Chinese population. In this study, we graded 98 FL cases; fluorescence in situ hybridization was used to determine the BCL2 and BCL6 translocation statuses, and these were compared with morphologic and immunohistochemical parameters. The expressions of the 4 antigens were B-cell leukemia/lymphoma (BCL)-2(88.8%), BCL-6(80.6%), CD10(62.2%), and Ki67(50.0%), respectively. The frequencies of BCL2 and BCL6 translocations were 58.5% and 16.3%. In conclusion, the incidence of IgH/BCL2-positive FL in Chinese patients is relatively lower compared with that in western countries. BCL2 translocation strongly correlated with CD10 and Ki67 expression. Our data confirm the presence of a relationship between the translocation status and the FL histologic grade. All BCL6 translocations occurred in high-grade FL, and this suggests that FL carrying BCL6 translocation probably constitute a special biological subtype.

[Significance of MUM-1/IRF4 protein expression in follicular lymphoma].

OBJECTIVE: To study the expression of MUM-1/IRF4 and its significance in follicular lymphoma. METHODS: Ninety-eight cases of follicular lymphoma were enrolled into the study. They were graded according to the 2008 WHO criteria. The expression of MUM-1/IRF4 protein and other markers (CD10, bcl-6, bcl-2 and Ki-67) was studied using tissue microarray and immunohistochemistry. RESULTS: Amongst the 98 cases studied, there were 24 grade 1 cases, 30 grade 2 cases, 26 grade 3A cases and 18 were grade 3B cases. The rates of expression of MUM-1/IRF4, CD10, bcl-6, bcl-2 and Ki-67 (≥ 25%) were 39.8% (39/98), 62.2% (61/98), 80.6% (79/98), 87.8% (86/98) and 50.0% (49/98), respectively. MUM-1/IRF4 predominantly expressed in high-grade follicular lymphoma and showed a significantly positive correlation with lymphoma grade (r = 0.628, P = 0.000) and Ki-67 index (r = 0.473, P = 0.000). MUM-1/IRF4 expression had a significantly negative correlation with CD10 expression (r = -0.597, P = 0.000), but no correlation with bcl-6 and bcl-2 expression. CONCLUSIONS: MUM-1/IRF4 expression is significantly higher in high-grade follicular lymphoma, indicating that these cases have a high proliferative activity, more aggressive behavior and poorer prognosis. MUM-1/IRF4, when strongly expressed, is another helpful marker for the diagnosis of high-grade follicular lymphoma.