Primary large cell neuroendocrine carcinoma of the bladder:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

Molecular genetics and immunohistochemistry characterization of uncommon and recently described renal cell carcinomas

Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.

Signif icance of Sentinel Lymph Node Biopsy and Immunohistochemistry in Diagnosis and Staging of Stage-cN0 Oral Squamous Cell Carcinoma

OBJECTIVE To assess the significance of sentinel lymph node biopsy （SLNB）, serial section and cytokeratin immunohistochemical staining in the diagnosis and staging of Stage-cNO oral squamous cell carcinoma （OSCC）, METHODS A blue stain, 99mTc-dextran SPECT lymphoscintigrapgy and intraoperative y-ray probes were used to examine the sentinel nodes in 31 cases with Stage-oNO oral cancer, The H＆E staining and a cytokeratin AE1/ AE3 immunohistochemistry （IHC） assessment, with serial sections, were conducted to provide results obtained from a routine pathological examination of lymph nodes, The value of the routine pathological examination of the sentinel lymph node （SLN）, serial sections and IHC determination for cervical lymph node metastasis of Stage-cN0 OSCC was appraised, RESULTS A total of 45, 55 and 51 SLNs were examined in 25 （80%）, 31 （100%） and 30 （96,5%） of the cases, by using the blue stain, y-ray probes, and SPECT lymphoscintigraphy, respectively, The average SLNs found in each case of the groups was 1,4 （1 to 3） and there were 1,302 non-NSLNs, Six positive SLN metastases were detected by routine pathological examination, among which 1 case was found to be an accompanied positive metastasis of non-SLN, One positive SLN metastasis was found after examination of serial sections plus routine H＆E staining and 2 were detected using serial sections plus AE3 immunohistochemical staining methods, No positive NSLNs were found in the study, CONCLUSION In order to make more progress in accurate SLNB diagnosis, serial sections and IHC （AE1/AE3） methods can be used for examination of the micrometastases which are difficult to identify by routine pathological sections and H＆E staining.

The Expression of RECK mRNA and Protein in Esophageal Squamous Cell Carcinoma and Its Clinical Significance

OBJECTIVE To investigate the expression of RECK mRNA and protein in esophageal squamous cell carcinoma （ESCC） and to examine its relationship with the clinicopathologic features. METHODS The expression of RECK mRNA and protein in 62 cases of ESCC, 31 of paraneoplastic atypical hyperplasia （PAH） and 62 normal esophageal mucous membrane specimens was examined, using RT-PCR and immunohistochemistry. RESULTS During canceration of the ESCC, the mRNA of RECK increased sequentially from ESCC tissue to PAH and normal mucous membranes. Values were 1.052±0.078, 1.274±0.235 and 1.306±0.121, respectively, with a significant difference among different groups （F=49.936, P〈0.05）. There was a statistically significant difference in the relative amount of the RECK mRNA among the ESCC tissues at various levels of differentiation, depth of infiltration, and different types of lymph node metastasis （F=5.081, F=26.084, U=24.011, P〈0.05）. In the ESCC tissue and PAH, the positive rates of RECK protein expressions were lower compared to the normal mucosa tissue, i.e. 59.7% （37/62）, 71.0% （22/31） and 85.5% （53/62）, respectively. There was a significant difference among the inter-group comparisons （Х^2=10.331, P〈0.01）. In ESCC, there was a close correlation between the RECK protein expression and the degree of cancer differentiation, and the depth of invasion and the types of ESCC lymph node metastasis （P〈 0.05）. CONCLUSION The decrease in expression of both RECK mRNA and protein in ESCC suggest that these low expressions may relate to ESCC development. Examination of RECK mRNA and protein expression may develop into one of the molecular indices for early ESCC diagnosis and prognosis.

Expression and Significance of PTEN in Bladder Transitional Cell Carcinoma

Objective： To explore the expression of anti-oncogene PTEN in bladder transitional cell carcinoma and its clinical significance. Methods： Using immunohistochemical S-P methods, the expression of PTEN gene was detected in 62 specimens of bladder cancer and 18 specimens of normal bladder tissue. Results： In the 62 bladder cancers, the positive rate of PTEN was 53.2% （33/62）. All 18 normal bladder tissues were positive for the PTEN expression. The expression of PTEN was negatively correlated to tumor grades （P〈0.05）. Conclusion： The reduced expression of PETN might play an important role in carcinogenesis and progression of bladder cancer. Detection of PTEN might be useful for judgement of tumor development and prognosis.

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.

Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma

AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed. RESULTS: The percentage of positive cases for MMP-9 detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P= 0.001<0.01), existence of vessel permeation (P= 0.027<0.05) and lymph node metastasis (P=0.027<0.05). CONCLUSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC.

Prognostic relevance of β-catenin expression in T2-3N0M0 esophageal squamous cell carcinoma

AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC speci-mens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating char-acteristic curve analysis was used to select the cut-off score for high or low IHC reactivity. Then, correlation of β-catenin expression with clinicopathological features and prognosis of ESCC patients was determined. RESULTS: No significant correlation was observed between β-catenin expression and clinicopathological parameters in terms of gender, age, tumor size, tumor grade, tumor location, depth of invasion and pathologi-cal stage. The Kaplan-Meier survival curve showed that the up-regulated expression of β-catenin indicated a poorer post-operative survival rate of ESCC patients at stage T2-3N0M0 (P = 0.004), especially of those with T3 lesions (P = 0.014) or with stage ⅡB diseases (P = 0.007). Multivariate analysis also confirmed that β-catenin was an independent prognostic factor for the overall survival rate of ESCC patients at stage T2-3N0M0 (relative risk = 1.642, 95% CI: 1.159-2.327, P = 0.005). CONCLUSION: Elevated β-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage ⅡB diseases.

Evidence of human papilloma virus infection and its epidemiology in esophageal squamous cell carcinoma

AIM： To look for the evidence of human papilloma virus （HPV） infection in esophageal squamous cell carcinomas （ESCC） and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants. METHODS： Papilloma virus （PV） and HPV were determined by UltrasensiveTM S-P immunohistochemistry （IHC） and in situ hybridization （ISH） in esophageal carcinoma tissues （82 cases） and the normal mucosa （40 cases）. RESULTS： IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV （16/18-E6） positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV （16/18-E6） were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV （16/18） DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV （16/18） DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens （P〈0.05）. The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens （P〉0.05）.CONCLUSION： HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squarnous cell carcinoma. HPV infection may play an important role in esophageal squarnous cell carcinoma.

Correlation of matrix metalloproteinase suppressor genes RECK,VEGF,and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma

AIM: To explore the expression of reversion inducing cysteine-rich protein with Kazal motifs (RECK), vascular endothelial growth factor (VEGF) and endoglin (CD105) protein and its correlation with occurrence, development, invasion and metastasis in esophageal squamous cell carcinoma (ESCC). METHODS: Streptavidin-peroxidase (SP) immunohisto- chemistry was used to detect expression of RECK and VEGF in 62 cases of ESCC, 31 cases of adjacent atypical hyperplastic epithelium and 62 cases of normal esophageal epithelium. CD105 Mb was used to assess microvessel density (MVD). RESULTS: The expression of RECK was closely correlated with histological grade, infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK decreased during cancer development: normal esophageal epithelium (85.5%, 53/62), adjacent atypical hyperplastic epithelium (71.0%, 22/31), and carcinoma (59.7%, 37/62). There was a significant difference among the groups (P < 0.05). The expression of VEGF protein was closely correlated with infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of VEGF protein increased during cancer development: normal esophageal epithelium (29.0%, 18/62), adjacent atypical hyperplastic epithelium (54.8%, 17/31), and carcinoma (67.7%, 42/62). There was a significant difference among the groups (P < 0.05). MVDCD105 increased in accordance with histological grade, butthere was no significant difference (grade Ⅰ, 36.92 ± 10.85; grade Ⅱ, 37.65 ± 9.50; and grade Ⅲ, 38.06 ± 12.19). The MVDCD105 was closely correlated with infiltration and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK was inversely correlated with the expression of VEGF and CD105. CONCLUSION: RECK, VEGF and CD105 play important roles in the infiltration, metastasis and carcinogenesis in esophageal carcinoma. Angiogenesis in ESCC may be promoted by over-expression of CD105.

Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder （TCCB） and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB （P〈0.05）, but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB （P〉0.05）. The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples （P〈0.05）. Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant （r=0.316, P〈0.05）. It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7±61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P<0.01). In contrast, the protein level of p27 was signifi cantly lower in ESCC than in normal squamous epithelium (182.0 ±69.0 vs 266.4±28.0, P<0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0±42.3 vs 83.0 ± 66.5, P<0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8±31.7 vs 98.4± 84.8, 32.0 ± 19.0 vs 54.1 ±53.7,206.2±61.5 vs 123.5±68.3, respectively, all P<0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r=0.270, 0.233 and-0.311, respectively, all P<0.05).CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.

Reversing effect of Tanshinone on malignant phenotypes of human hepatocarcinoma cell line

AIM To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation was detected.RESULTS The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid. Flow cytometric assay demonstrated that S phase cells decreased and G0/G1 phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased.CONCLUSION Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.

Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma

AIM： To study the relationship between the expression of human chorionic gonadotropin （HCG）, CD44v6, CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS： By labeled streptavidin-biotin technique, the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined. RESULTS： The positive rate of HCG expression in patients with lymph node metastasis was 85.71% （18/21）, higher than that （57.14%, 12/21） in those without lymph node metastasis （P〈0.05）. The positive rate of CD44v6 expression was 71.43% （15/21） in lymph node metastasis group, and 38.09% （8/21） in nonmetastasis group; there was a significant difference between the two groups （P〈0.05）. The positive rate of CD44v4/5 expression was 76.19% （16/21） in lymph node metastasis group, and 42.86% （9/21） in non-metastasis group; there was also a significant difference between them （P〈0.05）. From grade Ⅰ to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% （11/13）, 70.59% （12/17） and 58.33% （7/12）, respectively, there was no significant difference among them （P〉0.05）. The positive rate of CD44v6 expression in grades Ⅰ-Ⅲ of cancer tissues was 76.92% （10/13）, 52.94% （9/17）, and 33.33% （4/12） respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% （9/13）, 64.71% （11/17）, and 41.67% （5/12） respectively; there was no significant difference among the three groups. There was no correlation between the positive rates of HCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION： Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma

Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.

Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the differences in the expression of DNMT1 in 89 ecRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines （786-0 and Caki-1） were assessed after transfection with DNMT1 siRNA. Results： We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues （56.2% and 27.3%, respectively, P=0.018）. The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions： Expression of DNMTI protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.

Expression of thymidylate synthase and glutathione-stransferase π in patients with esophageal squamous cell carcinoma

AIM： To investigate the expression of thymidylate synthase （TS） and glutathione-s-transferase π （GST-π） in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS： Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma （ESCC） tissue sections from 102 patients （median age, 58 years） and in 28 normal esophageal mucosa （NEM） samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS： The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples （P 〈 0.05）. The expression level of TS was not only significantly lower in well-differentiated （21.88%） than in poorly-differentiated carcinomas （51.43%, P 〈 0.05）, but was also significantly higher in samples from male patients （46.51%） than from female patients （18.75%, P 〈 0.05）. GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples （P 〈 0.05）. The expression level of GST-π was also significantly higher in welldifferentiated carcinomas （65.63%） than in poorly- differentiated carcinomas （35.00%, P 〈 0.05）. CONCLUSION： The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of T5 and reduced expression of GST-π.

Upregulation of vimentin and aberrant expression of E-cadherin /beta-catenin complex in oral squamous cell carcinomas:correlation with the clinicopathological features and patient outcome

Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined the expression of vimentin,E-cadherin,and beta-catenin in 83 oral squamous cell carcinoma patients,and the relationships between the expression of these markers and specific clinicopathological features were analysed.The high expression of vimentin was observed in 23 of 43(53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death(P < 0.001 and < 0.001,respectively).The decreased expression of E-cadherin was observed in 36 of 43(84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death(P < 0.001 and < 0.001,respectively).Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed,decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death(P=0.002 and 0.002,respectively).The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses.Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients.The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.

Methylation of TIMP3 in esophageal squamous cell carcinoma

AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China.METHODS: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2’-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by immunohistochemistry.RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China.