Tumor Differentiation In Patients Research Articles

Von Willebrand factor and gastric cancer – is there an association? – A pilot study from South India

Background: Gastric adenocarcinoma in Indian patients’ is on the rise. A high level of plasma von Willebrand factor (vWF) is associated not only with the development of cancerassociated thrombosis but also with the degree of malignancy, the rate of metastasis, andcancer prognosis. Aims and Objectives: The aim of this study was to study the association of vWF with tumor location, TNM staging, and grades of tumor differentiation in gastric adenocarcinoma and to assess the usefulness of circulating vWF levels as a potential biomarker for gastric adenocarcinoma. Materials and Methods: This study is a prospective observational study done in the Department of Surgical Gastroenterology, Madurai Medical College, Madurai, over a period of 2 years between September 2020 and August 2022. Fifty cases of gastric cancer and 50 controls were recruited and vWF levels were analyzed. Results: Among the 50 gastric cancer patients, 8% belonged to Stage II, 62% belonged to Stage III, and 30% belonged to Stage IV. vWF was elevated in Gastric Cancer patients compared to control group. Mean value of vWF in Cases and Control population was 3.68 ng/ml and 0.58 ng/ml respectively (p value 0.0005). Pertaining to Stage, the vWF value was, Stage II – 4.7, Stage III – 3.3, and Stage IV – 4.1 ng/mL. With respect to tumor differentiation, the vWF values were, poorly differentiated – 4.7, moderately differentiated – 3.0, and well differentiated – 3.9 ng/mL. Conclusion: vWF values were significantly elevated in gastric cancer patients. Based on the results, vWF can be used as a surrogate marker to predict the tumor differentiation in patients, thereby prognosticating the disease. Stage-wise, there was no significantdifference in the vWF values.

CDC25B Is a Prognostic Biomarker Associated With Immune Infiltration and Drug Sensitivity in Hepatocellular Carcinoma.

Cell division cycle 25B (CDC25B), a member of the CDC25 phosphatase family, plays a key role in cell cycle regulation. Studies have suggested its carcinogenic potential in various cancers, but the role of CDC25B in the development of hepatocellular carcinoma (HCC) remains poorly understood. The aim of this study was to clarify the role of CDC25B in HCC using bioinformatics and experiments. CDC25B expression data of HCC cancer tissues and paracancerous normal samples were obtained from The Cancer Gene Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the relationship between CDC25B expression and the prognosis and degree of tumor differentiation of HCC patients was analyzed. CDC25B expression was verified in clinical HCC tissue samples using fluorescence quantitative polymerase chain reaction (q-PCR) and protein immunoblotting (Western blot). Gene set enrichment analysis (GSEA) was used to identify signaling pathways enriched in CDC25B expression, and differential genes (DEGs) were used to screen out coexpressed hub genes and construct protein-protein interaction (PPI) networks. 5-Ethynyl-2'-deoxyuridine (EDU) staining was used to compare the proliferation and differentiation ability of the HCC cell line (HCC-LM3) after knockdown of CDC25B. Finally, we investigated the mutation of CDC25B in HCC and the relationship between CDC25B expression and tumor cell infiltration of lymphocytes and some immune checkpoints as well as drug sensitivity. CDC25B was overexpressed in HCC tissues and correlated with poor prognosis and the degree of tumor differentiation in patients with HCC. The GSEA and PPI networks together revealed significantly upregulated signaling pathways, as well as functions, associated with the development of HCC when CDC25B was overexpressed. The EDU assay demonstrated that the ability of cells to differentiate value addedly was markedly reduced following the downregulation of CDC25B expression in HCC-LM3s. CDC25B was also involved in the formation of the tumor microenvironment (TME) and immune processes in HCC, and the high expression of CDC25B made patients less sensitive to some drugs. CDC25B can be used as a biomarker and immunotherapeutic target for poor prognosis and partial drug sensitivity in HCC, providing new ideas for HCC treatment.

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS.

Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated. To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression. Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis. The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC. This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Clinical and morphological features of bladder cancer course in HPV-infected patients

Purpose of the study. To study the histological type, grade of tumor differentiation in patients with primary and recurrent clinically non-muscle-invasive bladder cancer (NMIBC) with highly carcinogenic human papillomavirus (HPV) infection.Patients and methods. Formalin-fixed and paraffin-embedded bladder tumor tissue samples have been studied in 159 patients who underwent transurethral resection (TUR) of the bladder, for the presence of HPV DNA. To detect, quantify and differentiate DNA of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 genotypes in the samples, the AmpliSense® HPV HRC genotype-titer-FL was used. The result of the study was taken into account when the amount of DNA of the β-globin gene was at least 1000 copies per reaction. In order to statistically analyze our data we used the Fisher exact test and also calculated the odds ratio (OR) and 95 % CI.Results. According to the results of the study, out of 159 patients, high-risk HPV DNA was detected in the tumor tissue in 59 (37.1 %), of which HPV type 16 was found in 52 patients (89.4 %), HPV 18 was detected in 4 patients type (6.7 %) and type 35 in 3 (5.08 %). In a morphological study of the tissues of HPV-positive patients, the grade of tumor differentiation was G2 in 18 cases (30.5 %), G3 in 37 blocks, and G1 was detected only in 4 cases (6.7 %). In the presence of HPV, the chance of detecting a stage G3 tumor increases by 4.3 times. According to the received data, we can assume that there is a close relationship between detection in HPV patients of high-risk genotypes with moderately differentiated and low-differentiated forms of bladder cancer.Conclusion. this study may indicate that HPV infection affects the grade of tumor differentiation, and this, in turn, may allow the use of the HPV test to assess the nature of the development of relapse and/or progression of the disease.

SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells.

Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells' neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells' neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells' neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation.

A Survey of Human Papillomavirus and Epstein-Barr virus Immunohistochemical Status in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC).

Head and neck cancers are among the most prevalent cancers in the body. The aim of this study was to evaluate the expression of P16 and Epstein-Barr virus/latent membrane protein (EBV/LMP1) markers by immunohistochemistry in patients with squamous cell carcinoma of the head and neck. In this study, all tissue samples of head and neck biopsies from 75 patients with confirmed diagnosis of squamous cell carcinoma (HNSCC) during 2016 to 2018 who admitted to the pathology laboratory of Imam Khomeini Hospital, Iran were selected. Paraffin blocks which prepared from these tissue samples were obtained. The slides were prepared from all samples for routine Hematoxylin-Eosin and immunohistochemical staining to evaluate the expression of EBV/LMP1 and P16 markers in cancer cells. The mean age of patients was 63 years and most patients (85.3%) were male in 75 patients with HNSCC. There was a significant relationship between EBV/LMP1 biomarker expression and vascular invasion in patients (p < 0.05). There was no relationship between EBV/LMP1 biomarker expression and age, sex ,anatomical site of tumor and tumor differentiation of patients (p > 0.05). There was no relationship between P16 biomarker expression and age, sex, tumor differentiation, anatomical site of tumor and vascular invasion of patients (p > 0.05). There is a significant relationship between P16 biomarker and EBV/LMP1 biomarker staining (p < 0.05). The level of P16 positive biomarker was high in patients with HNSCC. However, the EBV/LMP1 positive biomarker was moderate in patients. There was a relationship between EBV/LMP1 biomarker expression and vascular invasion in HNSCC patients, as well as between P16 biomarker and EBV/LMP1 biomarker staining.

Epigenetic Markers of Colorectal Cancer: Clinical Data Analysis

The aim of the study was to systematize the results of clinical application of epigenetic biomarkers "microRNA" and "DNA methylation" in early diagnosis and prognosis in patients with colorectal cancer.&#x0D; Material and methods. Data review was conducted by the keywords "colorectal cancer" with "miRNA" or "methylation" in PubMed, Cochrane Library, ScienceDirect, ELECTRONIC LIBRARY and was limited by the period 2016-2021. In addition, a manual search for articles in peer-reviewed journals was performed. Exclusion criteria were: description of separate clinical cases; books and documents; experimental oncology in laboratory animals, comparison of therapeutic results of patients receiving chemotherapy. Out of 139 initially identified, 37 sources were included in the final analysis, of which 20 meta-analyzes, 1 randomized clinical trial, 14 systematic reviews and 2 practical guidelines.&#x0D; Results. Based on the analysis of clinical data, it has been established that the optimal environment for miR isolation for early diagnosis of colorectal cancer is the intestinal wall, furthermore, miR-139 has a proven diagnostic value. At the later stages of tumor development, fecal miRs, namely miR-21, can also be used as a screening method. MiR-181a, miR-181b, miR-20a, miR-10b and miR-145 are highly sensitive predictors of overall survival in colorectal cancer patients. They can potentially be considered as prognostic biomarkers and as decisions when administering adjuvant chemotherapy. miR21, miR106a, miR143, miR 150 and miR215 are most commonly used in clinical practice to determine the prognosis of treatment. Tumor and paratumor tissues can also be differentiated from the normal colon tissue in a healthy person by methylation of the SFRP2, SFRP1, TFPI2, BMP3, NDRG4, SPG20, BMP3 and NDRG4, SFRP1, 2, 4, 5, hMLH1 and RASSF1A genes. The analysis of methylated SEPT9 genes is the most informative of them: an increased weight of the mitylated SEPT9 gene directly correlates with progression and low tumor differentiation in patients with colorectal cancer.&#x0D; Conclusion. Literature data confirm that changes in the concentration of microRNA and methylated DNA in the environments of the human body correlate with the risk of oncogenesis, progression and invasion of colorectal cancer. It is reasonable to use a diagnostic algorithm differentiated by the analyzed tissues (blood, intestinal tissue, feces, urine), the expected stage of tumor development, diagnostic tasks (screening, survival prognosis) for the effective use of epigenetic markers of colorectal cancer in the clinical practice.

Linc00426 accelerates lung adenocarcinoma progression by regulating miR-455-5p as a molecular sponge

Increasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.

Clinical significance of ring finger protein 2 high expression in skin squamous cell carcinoma.

Although ring finger protein 2 (RNF2) serves an important role in the occurrence, development and regulation of various types of cancer, RNF2 expression in skin squamous cell carcinoma (SCC) remains unknown. The aim of the present study was to investigate the role of RNF2 expression in SCC and adjacent tissues from patients. The protein and gene expression levels of RNF2 in SCC and adjacent tissues were detected by immunohistochemistry (IHC), western blot analysis and semi-quantitative reverse transcription (RT) PCR. Single factor analysis was used to study the association between RNF2 expression level and the clinicopathological characteristics of patients with SCC. Multifactor Cox survival analysis was used to examine the association between RNF2 expression and the overall survival rate of postoperative patients with SCC. The results from IHC staining demonstrated that the positive expression rate of RNF2 was 84.68% (210/248) and 56.05% (139/248) in SCC and in adjacent tissues, respectively. Furthermore, results from western blot analysis demonstrated that RNF2 protein expression in SCC tissues was significantly higher compared with that in the adjacent tissues (P<0.05). The positive rate of RNF2 mRNA in SCC was 81.05% (201/248), which was significantly higher compared with that in the adjacent tissues 54.44% (135/248; P<0.05). Furthermore, RNF2 protein and gene expression levels were associated with tumor diameter, tumor stage, tumor metastasis and the degree of tumor differentiation in patients with SCC. Patients exhibiting higher RNF2 protein expression in SCC tissues had a significantly shorter disease-specific survival rate compared with patients with low RNF2 expression. In addition, RNF2 protein expression, tumor diameter, tumors site and tumor stage were independent factors affecting the overall survival rate of postoperative patients. High protein and gene expression levels of RNF2 in SCC tissues may be associated with the occurrence and development of SCC and prognosis of patients. The results form this study may serve the development of novel therapeutic options and diagnostic strategies for patients with SCC.

AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients.

Liver cancer is one of the most common malignant tumors, with the death rate ranking fourth among all types of cancer. Over the past few decades, several studies have reported that liver tumorigenesis is associated with dysfunction in autophagy. However, the detailed mechanism remains unclear. In this paper, we used tissue micro-array (TMA) of liver cancer to detect proteins associated with the regulation of autophagic signaling in non-cancerous and cancerous regions by immunohistochemical staining. Those proteins contained 4-HNE, p-AMPK, Erk1/2, p-Erk1/2, CARM1, TFEB, LAMP1, and p62. According to the degrees of tumor differentiation in patients (well differentiated group vs. moderately and poorly differentiated group), we analyzed each protein's expression in the ratio of the “cancerous region/non-cancerous region” in two groups. Current data showed that there were AMPK-ERK/CARM1 autophagic signaling pathways during the formation of liver cancer. The above-mentioned changes in signals indicated an upregulation of autophagy in cancerous regions, which means overactivated autophagy plays an important role in liver cancer.

Four hundred fifty-three consecutive pancreaticoduodenectomies with pancreaticogastrostomy

BackgroundPatients who undergo pancreaticoduodenectomy (PD) have the pancreatic remnant (PR) anastomosed to the jejunum. In this study, all patients had the PR anastomosed to the stomach. Our aims are to evaluate postoperative outcomes of patients undergoing PD with pancreaticogastrostomy (PG). MethodsThere was 453 patients who underwent PD with PG. Preoperative characteristics, intraoperative data, and postoperative outcomes were analyzed using univariate and multivariate models. ResultsThe patient cohort had a median age of 67 years and underwent resection for pancreatic (40.8%), ampullary (15.9%), duodenal (6.6%), distal bile duct (6.4%) cancers. Multivariate analysis revealed poor prognosis was related to age, tumor diameter, lymph node ratio, perineural invasion, and tumor differentiation in patients with periampullary adenocarcinoma. ConclusionsThis series of patients undergoing PD with PG shows that the operation can be performed safely with excellent outcomes for a variety of malignant and benign conditions.

A Radiomics Signature in Preoperative Predicting Degree of Tumor Differentiation in Patients with Non–small Cell Lung Cancer

Poorly differentiated non-small cell lung cancer (NSCLC) indicated a poor prognosis and well-differentiated NSCLC indicates a noninvasive nature and good prognosis. The purpose of this study was to build and validate a radiomics signature to predict the degree of tumor differentiation (DTD) for patients with NSCLC. A total of 487 patients with pathologically diagnosed NSCLC were retrospectively included in our study. Five hundred ninety-one radiomics features were extracted from each tumor from the contrast-enhanced computed tomography images. A minimum redundancy maximum relevance algorithm and a logistic regression model were used for dimension reduction, feature selection, and radiomics signature building. The performance of the radiomics signature was assessed using receiver operating characteristic analysis, and the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to quantify the association between a signature and DTD. An independent validation set contained 184 consecutive patients with NSCLC. A nine-radiomics-feature-based signature was built and it could differentiate low and high DTDs in the training set (AUC = 0.763, sensitivity = 0.750, specificity = 0.665, and accuracy = 0.687), and the radiomics signature had good discrimination performance in the validation set (AUC = 0.782, sensitivity = 0.608, specificity = 0.752, and accuracy = 0.712). A radiomics signature based on contrast-enhanced computed tomography imaging is a potentially useful imaging biomarker for differentiating low from high DTD in patients with NSCLC.

Expression of miR-711 and mechanism of proliferation and apoptosis in human gastric carcinoma.

[This retracts the article DOI: 10.3892/ol.2017.6777.].

Prognostic value of NM23 in patients with gastric cancer: A systematic review and meta-analysis.

NM23, as a possible biomarker of prognosis in malignant tumors, has generated remarkable interest in this critical period of the high morbidity and mortality of malignancies. Thus, we launched this meta-analysis to investigate the predictive value of NM23 expression in patients with gastric cancer. We searched PubMed, Embase, and Web of Science for relevant articles. The pooled odds ratios (ORs) and corresponding 95% confidence interval (CI) were calculated to evaluate the prognostic value of NM23 expression in patients with gastric cancer and the association between NM23 expression and clinicopathological factors. We also performed subgroup analyses to find the source of heterogeneity. Exactly, 2674 patients were pooled from 19 available studies in total. The incorporative OR combined by 11 studies with overall survival (OS) showed no significance (OR = 0.90, 95% CI: 0.51-1.58, P = 0.71). Although we failed to find any significance in N status and tumor node metastasis (TNM) staging (P = 0.23 and P = 0.74, respectively), elevated NM23 expression was related to well tumor differentiation (OR = 0.62, 95% CI: 0.41-0.95, P = 0.03). However, in the subgroup analyses, we could not find any potential source of heterogeneity. The results showed that statistically significant association was found between NM23 expression and the tumor differentiation of patients with gastric cancer, but no significance was found in OS, N status, and TNM staging. More and further researches should be conducted to reveal the prognostic value of NM23.

Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma.

• PRSS3 is downregulated by intragenic hypermethylation in HCC. • Epigenetic silencing of PRSS3 facilitates growth, migration, and invasion of HCC. • PRSS3 intragenic methylation has implication in diagnosis of HCC.

Expression of miR-711 and mechanism of proliferation and apoptosis in human gastric carcinoma.

MicroRNAs (miRs) are involved in many aspects of cell biology, including cell proliferation and apoptosis, two critical aspects of tumor biology. We investigated the effect of miR-711 on Bcl-2 expression in human MGC803 gastric cancer cells and the mechanism of cell proliferation, apoptosis, and invasion. Expression of miR-711 and Bcl-2 was significantly increased in gastric adenocarcinoma compared to adjacent normal tissue. Inhibition of miR-711 in MGC803 gastric cancer cells decreased the expression of Bcl-2, decreased cell proliferation, decreased the invasion ability, and increased apoptosis. The expression of Bcl-2 protein correlated with clinical staging, lymph node metastasis, and tumor differentiation in patients with gastric cancer. The expression of miR-711 positively correlated with the expression of Bcl-2, suggesting that miR-711 and Bcl-2 are co-regulated and involved in the development of gastric cancer.

Tumor Growth Pattern is Significantly Associated with Metastasis in Patients Diagnosed with Colon Carcinoma – A Computer Image Analysis Study

Background and aim: Growth pattern of the tumor has been studied for its association with survival in colorectal cancer. Among different growth pattern evaluating techniques, very little is known about prognostic significance of complexity index. The aim of this study was to develop a prognostic model, which could be used to predict prognosis in the patients diagnosed with colon carcinoma. Materials and methods: Formalin fixed paraffin embedded tissues samples from 316 patients diagnosed with colon carcinoma were used in this study. The slides were stained for cytokeratin-8 and images of the invasive front of the tumor were captured using a camera mounted onto a microscope. Images were thresholded in order to get the tumor area black and the surrounding tissue white. The tumor outline was also highlighted as a single pixel line to calculate the fractal dimension and number of tumor cells and tumor cell clusters. These two features were then used to calculate the complexity index by performing a tree diagram analysis. Complexity index was correlated with 5-years survival and other clinicopathological data (age, gender, tumor penetration, lymph node metastasis, duke’s stages, anatomical localization and differentiation of the tumor) of the patients. Results: Clinicopathological parameters like tumor metastasis, localization, gender and differentiation were significantly associated with tumor complexity index with p=0.000, p=0.002, p=0.024 and p=0.000 respectively. A positive trend was also observed between complexity index of tumor and age variable (p=0.051). Tumor wall penetration, lymph node metastasis and Duke’s stages were not significantly associated with tumor growth pattern; complexity index with p=0.997, p=0.857, p=0.783 and p=0.647 respectively. Conclusion: We conclude that complexity index is associated with systemic metastasis and tumor differentiation in patients diagnosed with colon carcinoma. Complexity index is a reliable objective and quantitative technique used to analyse tumor characteristics and can be used as a prognostic tool in the individual treatment of colon carcinoma

Predictability of preoperative 18F-FDG PET for histopathological differentiation and early recurrence of primary malignant intrahepatic tumors.

The limited studies with 18F-fluorodeoxyglucose (18F-FDG)-PET reported results and interpretations that differed between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). We investigated the correlation between preoperative PET results and postoperative prognosis, including early (time-to-recurrence<6 months) tumor recurrence, and histopathological tumor differentiation in patients who had undergone surgery for primary malignant intrahepatic tumors, including HCC and IHCC. We retrospectively reviewed 357 patients who had undergone curative surgery for malignant hepatic tumors, including primary HCC or IHCC, other than Klatskin tumors at a tertiary academic hospital between January 2005 and June 2012. All patients had undergone an 18F-FDG PET/computed tomography scan preoperatively and the maximum standardized uptake value of the tumor (max SUV tumor) and the tumor-to-nontumor SUV ratio (TNR) were calculated from 18F-FDG uptake. Histopathological differentiation grading was confirmed postoperatively. Among the patients, 115 cases with primary malignant intrahepatic tumors fulfilled the inclusion criteria. On univariate analysis, preoperative max SUV tumor and TNR showed a correlation with the overall and early tumor recurrence of HCC, but only max SUV tumor was associated with overall and early recurrence of IHCC (P<0.05). When considering postoperative histopathological differentiation, a correlation between max SUV tumor and TNR with HCC and between max SUV tumor and IHCC was found (P<0.05). However, on multivariate analysis, only early recurrence was associated with TNR in HCC and with max SUV tumor in IHCC. A preoperative 18F-FDG PET scan can be considered a useful reference for postoperative tumor recurrence and histopathological differentiation in cases of primary malignant intrahepatic tumors. 18F-FDG PET scan results should be interpreted separately for malignant liver tumors.

TH‐C‐351‐08: Clustering Analysis of Dynamic 11C‐Methionine PET in GBM for RT Target Definition

Purpose: To assess tumor differentiation in patients with glioblastoma multiforme (GBM) using dynamic 11C‐methionin (D‐MET) PET and fuzzy c‐means (FCM) clustering analysis; and to evaluate the added value of D‐MET PET in radiation therapy (RT) target definition. Method and Materials: D‐MET PET images were obtained prior to RT in 25 patients with GBM. Each scan was composed of 15 phases acquired at 0–50 minutes following injection. Conventional MRI was also acquired before RT for target volume definition and after RT for evaluation of treatment outcome. D‐MET PET data were normalized to the mean uptake of each individual's cerebellum. Volume of interest (VOI) for the analysis was defined based on pre‐RT FLAIR‐MRI and extended to incorporate regions of high uptake of MET. Time‐activity curves of MET uptake in the VOI were classified using a FCM clustering algorithm with spatial constraints. The optimal number of clusters was determined for each dataset by calculating several clustering validity indices. The results of classification were reviewed by experts; and were also correlated to the patterns of local failure after RT. Results: Using the FCM clustering algorithm, time‐activity curves of MET uptake in the VOI were successfully partitioned into tumor, normal brain tissue, inflammation response, surgical cavity and edema. Heterogeneous MET uptake in the tumor was also differentiated. In 15 of the 25 patients who had tumor progression, the pre‐RT PET in the clusters correspondent to the locations of recurrence had a median uptake value of 1.47 (last dynamic phase), which involves clusters beyond the hottest ones. Conclusion: This study demonstrated that dynamic MET‐PET is capable of differentiating active tumors in patients with GBM. It is also promising in providing extra information for RT target definition.Supported by NIHP01CA59827.

Endometrial biopsy by means of the hysteroscopic resectoscope for the evaluation of tumor differentiation in endometrial cancer: A pilot study

Aims To assess the diagnostic accuracy of endometrial biopsy by means of the hysteroscopic resectoscope (EBHR) in evaluating tumor differentiation in patients with endometrial cancer. Methods Between January and December 2005, all the women with a diagnosis of endometrioid adenocarcinoma of the uterus, when admitted to hospital, were enrolled for this study. Patients eligible for surgical treatment underwent a preoperative work-up consisting in pelvic magnetic resonance imaging (MRI) and EBHR. In all patients submitted to a hysterectomy, a comparison between pre- and postoperative tumor grade was carried out. Results 42 women were enrolled in the study. Hysteroscopic biopsy was carried out in 39 patients (mean age 62,5 years, range 33–79; FIGO stage I: 34, stage II–IV: 5). No complication related to hysteroscopy was observed. The preoperative tumor grade by hysteroscopy correlated with the final grade in 97,1% of cases. No patient had positive peritoneal washing and after a median follow-up of ten months no intraperitoneal tumor relapse was observed. Conclusion EBHR is a very accurate diagnostic procedure for assessing the preoperative tumor grade in patients with endometrial cancer.