Comparative Assessment of E-cadherin's Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

ABSTRACT Objective: To identify the clinicopathological correlation of E-cadherin expression in metastatic and non-metastatic oral squamous cell carcinoma (OSCC). Material and Methods: A total of 90 paraffin-embedded tissue sections of OSCC were retrieved from the registry. The total selected samples were 45 cases each from the primary lesions of metastatic and non-metastatic OSCC. One section was subjected to routine Hematoxylin and eosin stain and another to immunohistochemical analysis for E-cadherin expression. Results: A non-significant (p˃0.05) increased expression is seen in the non-metastatic group compared to the metastatic group, with predominantly membrane as the staining site in either group. However, the expression of E-cadherin did not reveal any statistically significant association with independent variables such as age, gender, and adverse habits of the patients (p>0.05). On the other hand, with respect to the histological differentiation of OSCC, a significant association (p<0.001) was observed with the well-differentiated type of metastatic OSCC. Conclusion: E-cadherin was useful to some extent in predicting regional metastasis. However, further studies using a panel of biomarkers with increased sample size may help us understand the process involved in metastasis.

Correlations of expressions of tissue inhibitor of matrix metalloproteinase-1 and fibronectin 1 in pregnancy associated breast cancer with expression of E-cadherin and prognosis / 肿瘤研究与临床

Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.

Effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts / 中华皮肤科杂志

Objective:To investigate effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts.Methods:Immunohistochemical technique was used to detect ROCK1 protein expression in human keloids and normal skin tissues, and Western blot analysis was performed to detect the expression of ROCK1, transforming growth factor β1 (TGF-β1) and E-cadherin in keloid tissues. In vitro cultured human keloid fibroblasts (HKFs) were divided into 4 groups: ROCK1 gene overexpression control group (ROCK1 NC group) transfected with ROCK1 gene overexpression control vectors, ROCK1 gene overexpression group (ROCK1 OE group) transfected with ROCK1 gene overexpression vectors, ROCK1 gene knockdown control group (sh NC group) transfected with ROCK1 gene knockdown control vectors, and ROCK1 gene knockdown group (shROCK1 group) transfected with ROCK1 gene knockdown vectors. Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ROCK1 gene on the survival rate of HKFs, Transwell assay to evaluate the effect on the migration of HKFs, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of ROCK1, TGF-β1 and E-cadherin, respectively. Results:Immunohistochemical study showed that ROCK1 protein expression decreased significantly in the human keloid tissues compared with the normal tissues ( t = 6.47, P = 0.003) ; Western blot analysis showed that the expression levels of ROCK1 and E-cadherin significantly decreased ( t = 14.02, 162.20, respectively, both P < 0.001), while TGF-β1 expression significantly increased ( t = 76.01, P < 0.001) in the keloid tissues compared with the expression levels of corresponding proteins in the normal tissues. CCK8 assay showed that the cell activity was significantly lower in the ROCK1 OE group than in the ROCK1 NC group after 24-hour transfection ( t = 3.25, 3.78, P = 0.031, 0.019, respectively), and significantly higher in the shROCK1 group than in the sh NC group ( t = 3.12, 2.79, P = 0.036, 0.049, respectively). Transwell assay showed that the number of migratory cells was significantly lower in the ROCK1 OE group than in the ROCK1 NC group ( t = 5.17, P = 0.004), and significantly higher in the shROCK1 group than in the sh NC group ( t = 9.28, P < 0.001). Compared with the ROCK1 NC group, the ROCK1 OE group showed significantly increased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but decreased mRNA and protein expression levels of TGF-β1 (both P < 0.001) ; compared with the sh NC group, the shROCK1 group showed significantly decreased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but significantly increased mRNA and protein expression levels of TGF-β1 ( P = 0.005 or < 0.001) . Conclusions:The ROCK1 gene can inhibit the proliferation and migration of HKFs. Overexpression of the ROCK1 gene can down-regulate the TGF-β1 gene expression and up-regulate the E-cadherin gene expression in HKFs.

Study on Jianpi Bushen Jiedu Decoction for inhibiting epithelial-mesenchymal transformation of hepatocellular carcinoma through JAK2/STAT3 pathway / 国际中医中药杂志

Objective:To study the effects of Jianpi Bushen Jiedu Decoction on the epithelial-mesenchymal transformation of nude mice with HCCLM3 subcutaneous transplanted tumor by regulating JAK2/STAT3 pathway.Methods:HCCLM3 subcutaneous transplanted tumor model was established in mice. After the successful modeling, 24 nude mice were divided into blank group, TCM group and combined group according to random number table method, with 8 mice in each group. Mice in the TCM group were given 0.68 mg/ml alcohol extract of Jianpi Bushen Jiedu Decoction for gavage, and the combined group were given sorafenib suspension plus alcohol extract of Jianpi Bushen Jiedu Decoction 3.5 mg/ml for gavage, once a day, for consecutive 4 weeks. The effects of Jianpi Bushen Jiedu Decoction on tumor volume, tumor weight of HCCLM3 subcutaneous transplanted tumor and mice body weight were observed; Western blot was used to detect the expressions of E-cadherin, N-cadherin, Vimentin and JAK2/STAT3 pathway-related proteins in subcutaneous transplanted tumor tissues of hepatocellular carcinoma of mice in each group.Results:Compared with the control group, the average tumor weight of subcutaneous transplanted tumor decreased significantly in the TCM group and the combined group ( P<0.05), and the expressions of JAK2, STAT3, p-JAK2, p-STAT3, N-cadherin, and Vimentin decreased significantly in subcutaneous transplanted tumor tissue ( P<0.05), while E-cadherin increased ( P<0.05). Conclusion:Jianpi Bushen Jiedu Decoction can inhibit the growth of subcutaneous transplanted tumor of hepatocellular carcinoma in mice. The mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway, thereby inhibiting the epithelial-mesenchymal transformation of hepatocellular carcinoma.

Long non-coding RNA LINC00657 is a prognostic factor in diffuse-type adenocarcinoma on esophagogastric junction / 中华普通外科杂志

Objective:To study the expression and significance of long noncoding RNA (lncRNA) LINC00657 in diffuse-type adenocarcinoma of esophagogastric junction (AEG).Methods:RT-PCR was used to determine the expression of LINC00657 in AEG tissues and AEG patient-derived tumor cells (PDCs). The expression of E-cadherin in AEG tissues and PDCs was detected. The Kaplan-Meier method was used to evaluate the correlation of LINC00657 expression with the overall survival (OS) of patients.Results:LINC00657 was highly expressed in AEG tissues [(1.41±0.12) vs. (0.61±0.11), t=276.038, P<0.01] and PDCs, while E-cadherin was significantly down-regulated. The expression of LINC00657 was retated to tumor diamer, invassion depth, lymph node metastasis, TNM staging (all P<0.05) In Kaplan-Meier analysis, high levels of LINC00657 were associated with poor prognosis for patients with diffuse-type AEG. In addition, a significant inverse relationship was observed between LINC00657 and E-cadherin expression ( r=-0.529, P<0.001). Conclusions:Elevated expression of LINC00657 in diffuse-type AEG tissues is associated with poor prognosis and may confer a malignant phenotype upon tumor cells.

Expression of E-cadherin in cervical squamous cell carcinoma and its prognostic significance / 肿瘤研究与临床

Objective:To investigate the expression of E-cadherin (E-cad) in cervical squamous cell carcinoma and its prognostic significance.Methods:The clinical data of 80 patients with cervical squamous cell carcinoma who received radical radiotherapy in People's Hospital of Xinjiang Uyghur Autonomous Region from January 2013 to October 2016 were retrospectively analyzed. The expression of E-cad protein in cancer tissues was detected by using automatic immunohistochemistry and the relationship between its expression and clinicopathological features of patients with cervical squamous cell carcinoma was analyzed. Kaplan-Meier method was used to make survival analysis, and Cox proportional risk model was used to analyze the factors affecting the prognosis of patients.Results:Among 80 patients, 30 (37.5%) cases died, the median progression-free survival (PFS) time was 43.7 months (95% CI 46.3-62.4 months), and the median overall survival (OS) time was not reached. The low expression rate of E-cad was 53.75% (43/80). The low expression rate of E-cad in low differentiated patients was higher than that in middle and high differentiated patients [75.0% (21/28) vs. 42.3% (22/52), χ2 = 7.83, P = 0.005]; the low expression rate of E-cad in patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲ A-Ⅲ B was higher than that in those with stage Ⅰ B2-Ⅱ B [65.9% (31/47) vs. 36.5% (12/33), χ2 = 6.83, P = 0.012]. The PFS and OS of patients with low expression of E-cad were worse than those of patients with high expression of E-cad, and the differences were statistically significant ( χ2 = 5.51, P = 0.018; χ2 = 7.48, P = 0.006). Multivariate Cox regression analysis showed that E-cad low expression was an independent risk factor for PFS and OS in patients with cervical squamous cell carcinoma ( HR = 1.836, 95% CI 1.023-3.297, P < 0.05; HR = 2.439, 95% CI 1.091-5.698, P < 0.05). Conclusion:The low expression of E-cad is an important influencing factor for the poor prognosis of patients with cervical squamous cell carcinoma.

Expressão de e-caderina e claudina-3 no epitélio cólico após terapia com infliximabe: modelo experimental de colite de exclusão / Expression of e-cadherin and claudin-3 in the colonic epithelium after the infliximab therapy: experimental model of disuse colitis

RESUMO - RACIONAL: A etiopatogenia da colite por desuso (DC) ainda não foi totalmente elucidada. As principais teorias consideram que a doença pode estar relacionada ao aumento de bactérias anaeróbias, falta de suprimento de ácidos graxos de cadeia curta (AGCC) e distúrbios imunológicos que se desenvolvem em segmentos colorretais desprovidos de trânsito fecal. OBJETIVO: Verificar se a aplicação de infliximabe modifica o conteúdo tecidual das proteínas E-caderina e claudina-3 no epitélio cólico de ratos sem trânsito intestinal. MÉTODOS: Vinte dois ratos foram submetidos a derivação do trânsito intestinal pelo procedimento de Hartmann. Eles permaneceram com o ostoma por 12 semanas para permitir o desenvolvimento da colite de exclusão. Em seguida, foram divididos em três grupos experimentais: seis animais receberam 2,0 ml de solução salina/semana, oito infliximabe na dose de 5 mg/Kg/semana e, os demais, infliximabe na dose de 10 mg/Kg/semana por 5 semanas consecutivas. Em seguida, os animais foram eutanasiados e os segmentos cólicos com e sem trânsito intestinal foram removidos. A colite por desuso foi diagnosticada pelas alterações histológicas definidas por uma escala previamente validada. Expressão tecidual de E-caderina e claudina-3 foi avaliada por imuno-histoquímica, e o conteúdo tecidual de ambas as proteínas foi quantificado por análise de imagem assistida por computador. RESULTADOS: Segmentos cólicos exclusos de trânsito fecal apresentaram maior grau de inflamação do que os expostos ao trânsito fecal. Inflamação foi menor nos animais tratados com infliximabe, independente da dose utilizada. Níveis de E-caderina e claudina-3 estavam reduzidos no cólon excluso. O tratamento com infliximabe aumentou os níveis das proteínas em segmentos do cólon sem trânsito intestinal, principalmente nos animais que receberam a dose de 10mg/kg/semana. CONCLUSÃO: Infliximabe reduz inflamação nos segmentos do cólon excluso e aumenta o conteúdo tecidual de E-caderina e claudina-3, especialmente na concentração de 10mg/kg/semana.

ABSTRACT - BACKGROUND: The etiopathogenesis of disuse colitis (DC) has not yet been fully elucidated. The main theories consider that the disease may be related to an increase in anaerobic bacteria, the lack of short-chain fatty acid (SCFA) supply, and immunological disorders that develop in the colorectal segments devoid of fecal transit. AIM: The aim of this study was to verify whether the application of infliximab modifies the tissue content of E-cadherin and claudin-3 proteins in colonic epithelium of rats devoid of intestinal transit. METHODS: A total of 22 rats underwent intestinal transit bypass using Hartmann's procedure. They remained with the shunt for 12 weeks to allow the development of DC. Later, they were divided into three experimental groups: six animals received 2.0 mL saline solution/week, eight received infliximab at a dose of 5 mg/kg/week, and eight received infliximab at a dose of 10 mg/kg/week for 5 consecutive weeks. At the end of this period, the animals were euthanized, and the colonic segments with and without intestinal transit were removed. DC was diagnosed based on the histological changes defined by a previously validated scale. The tissue expression of E-cadherin and claudin-3 was assessed by immunohistochemistry, and the tissue content of both proteins was quantified by computer-aided image analysis. RESULTS: The colonic segments excluded from fecal transit showed a higher degree of inflammation than those exposed to fecal transit. The degree of inflammation was lower in animals treated with infliximab, regardless of the dose used. The levels of E-cadherin and claudin-3 were reduced in the excluded colon. Treating animals with infliximab increased the levels of both proteins in the colonic segments without intestinal transit, especially in animals receiving a dose of 10 mg/kg/week. CONCLUSION: Infliximab therapy reduces inflammation in the colonic segments excluded from intestinal transit and increases the tissue content of E-cadherin and claudin-3 proteins, especially when used at a concentration of 10 mg/kg/week.

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Vitamin D maintains E-cadherin intercellular junctions by downregulating MMP-9 production in human gingival keratinocytes treated by TNF-α

PURPOSE: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. METHODS: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha (TNF-α). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. RESULTS: TNF-α downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by TNF-α was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with TNF-α. In addition, vitamin D downregulated TNF-α-induced nuclear factor kappa B (NF-κB) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. CONCLUSIONS: These results suggest that vitamin D may avert TNF-α-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by TNF-α. Vitamin D may reinforce ECJs by downregulating NF-κB signaling, which is upregulated by TNF-α. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.

Expressions of PTEN and E-cadherin in breast cancer tissues and their clinical significance / 国际肿瘤学杂志

Objective To investigate the expressions of phosphatase and tensin homologue deleted on chromosome ten(PTEN)and epithelial cadherin(E-cadherin)in breast cancer tissues and explore their clini-cal significance. Methods We retrospectively analyzed the clinical data of 263 breast cancer patients admitted to the First Affiliated Hospital of Harbin Medical University from November 2012 to December 2014. The expressions of PTEN and E-cadherin were detected by immunohistochemistry. The relationship of protein ex-pression with clinicopathological characteristics was analyzed by χ2 test or Fisher exact test. Contingency corre-lation analysis was used to analyze the correlation between PTEN and E-cadherin,and Kaplan-Meier was used to evaluate the relationship between their expressions and patients' survival. COX regression model was used to analyze risk factors. Results The positive expression rates of PTEN and E-cadherin in breast cancer tissues were 68. 4％(180 / 263)and 95. 4％(251 / 263)respectively,lower than those in para-tumor breast tissues 77. 9％(205 / 263)and 98. 5％(259 / 263),with statistically significant differences(χ2 = 6. 056,P = 0. 014;χ2 = 4. 125,P = 0. 042). PTEN expression was associated with lymph node metastasis( χ2 = 8. 443,P =0. 015)and clinical stage(χ2 = 9. 253,P = 0. 010). E-cadherin expression was not correlated with age,meno-pausal status,tumor maximum diameter,lymph node metastasis and clinical stage(all P > 0. 05). Contingency correlation analysis showed a positive correlation between PTEN and E-cadherin expressions in breast cancer tissues(C = 0. 125,P = 0. 041). Survival analysis showed that the 5-year tumor-free survival rate was 81. 9％in the PTEN negative group,lower than 95. 0％ in the positive group(χ2 = 12. 040,P = 0. 001). The 5-year tumor-free survival rate in the E-cadherin negative group was 66. 7％ ,lower than 92. 0％ in the positive group (χ2 = 13. 313,P < 0. 001). COX multivariate analysis showed that negative expressions of PTEN and E-cadherin and lymph node metastasis were independent risk factors for the prognosis of breast cancer patients (HR = 2. 554,95％ CI:1. 016-6. 420,P = 0. 046;HR = 3. 573,95％ CI:1. 136-11. 239,P = 0. 029;HR =3. 622,95％ CI:2. 026-6. 476,P < 0. 001). Conclusion PTEN is related to E-cadherin expression and low expressions of both may be one of the mechanisms of breast cancer development,invasion and metastasis. Com-bined detection can be used as an indicator to determine the prognosis of breast cancer.

Expressions of Yes-associated protein 1 and collagen triple helix repeat containing 1 in triple-negative breast cancer and their correlations with expression of E-cadherin / 肿瘤研究与临床

Objective To investigate the clinical significances of the expressions of Yes-associated protein 1 (YAP1) and collagen triple helix repeat containing 1 (CTHRC1) in triple-negative breast cancer (TNBC) and their correlations with expression of E-cadherin. Methods Immunohistochemical analysis (SABC) was performed to detect expressions of YAP1 and CTHRC1 in 73 specimens of TNBC and adjacent cancer tissues collected from patients in Dandong First Hospital from January 2006 to December 2017. The correlations between the expressions of YAP1 and CTHRC1 and clinicopathologic features and E-cadherin expression were analyzed. Results The expression rates of YAP1 and CTHRC1 in TNBC were 71.23％(52/73) and 79.45％(58/73), and 13.70％(10/73) and 27.40％(20/73) in adjacent cancer tissues, respectively, and the differences were statistically significant (χ2 values were 49.452 and 39.748, both P< 0.01). The expressions of YAP1 and CTHRC1 were related to tumor grade, clinical stage and lymphatic metastasis (YAP1:χ2 values were 10.244, 8.754, and 6.914, all P<0.05;CTHRC1:χ2 values were 12.582, 13.172, and 6.400, all P< 0.05), but they were not related to patient's age, tumor diameter and menopausal status (all P>0.05). The expressions of YAP1 and CTHRC1 were negatively correlated with expression of E-cadherin in TNBC (r=-0.371, P=0.001;r=-0.323, P=0.005). Conclusion YAP1 and CTHRC1 is closely related to the occurrence and development of TNBC and may participate in the invasion of TNBC through epithelial mesenchymal transition.

Correlation of metallothionein-2A, E-cadherin and cyclin E with biochemical recurrence in prostate cancer / 肿瘤研究与临床

Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5％ (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8％(8/54), 38.7％(24/62) and 58.3％ (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95％CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95％CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95％CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95％ CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.

Prognostic value of serum P-cadherin level in patients with non-small cell lung cancer / 国际肿瘤学杂志

Objective To investigate the prognostic value of serum P-cadherin( P-cad)level in patients with non-small cell lung cancer(NSCLC). Methods A total of 80 patients with NSCLC in Hanzhong 3201 Hospital of Shaanxi Province from January 2012 to December 2013 were selected as study subjects. The relationships between serum P-cad level and clinicopathological characteristics were analyzed. The Cox regres-sion analysis was used to analyze the risk factors affecting prognosis of NSCLC patients. The survival curve was drawn by Kaplan-Meier method and the difference test was carried out by log-rank method. Results There were significant differences in lymph node metastasis(χ2 = 14. 31,P < 0. 001),vascular invasion(χ2 = 5. 56, P = 0. 018)among NSCLC patients with different levels of serum P-cad. Multivariate Cox regression analysis showed that lymph node metastasis(HR = 0. 856,95％ CI:0. 702-0. 955,P = 0. 012),TNM stage(ⅢA HR =1. 315,95％ CI:1. 058-1. 991,P = 0. 024;ⅢB HR = 1. 448,95％ CI:1. 124-2. 215,P = 0. 011;Ⅳ HR =1. 569,95％ CI:1. 182-2. 441,P < 0. 001)and high level of serum P-cad(HR = 1. 815,95％ CI:1. 224-3. 562,P < 0. 001)were risk factors for progression-free survival in NSCLC patients,and lymph node metasta-sis(HR = 0. 755,95％ CI:0. 652-0. 915,P = 0. 022),poor differentiation(HR = 1. 622,95％ CI:1. 112-2. 015,P < 0. 001),TNM stage(ⅢA HR = 1. 335,95％ CI:1. 064-2. 014,P = 0. 011;ⅢB HR = 1. 489, 95％ CI:1. 129-2. 297,P < 0. 001;Ⅳ HR = 1. 622,95％ CI:1. 192-2. 501,P < 0. 001)and high level of serum P-cad(HR = 1. 677,95％ CI:1. 193-2. 668,P < 0. 001)were risk factors for overall survival of NSCLC patients. The results of Kaplan-Meier survival curve showed that the overall survival and progression-free survival of patients with high level of serum P-cad were shorter than those of patients with low level of serum P-cad(χ2 = 5. 18,P = 0. 015;χ2 = 5. 48,P = 0. 011). Conclusion High level of serum P-cad is closely related to poor prognosis in NSCLC patients.

Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly

Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

Inmunoexpresión de E-cadherina y vimentina en mucosa oral normal, displasia epitelial oral y carcinoma oral de células escamosas / Immunoexpression of E-cadherin and vimentin in normal oral mucosa, oral epithelial displasia and oral squamous cell carcinoma

El objetivo fue evaluar la inmunoexpresión de E-cadherina y Vimentina en mucosa oral normal (MON), displasia epitelial oral (DEO) y carcinoma oral de células escamosas (COCE). Se realizó un estudio descriptivo de una serie de casos analizandolos mediante técnica de inmunohistoquímica contra E-cadherina y Vimentina 16 muestras de MON, 16 de DEO y 19 de COCE. La inmunotinción fue evaluada cualitativamente considerando extensión e intensidad para E-cadherina e intensidad para Vimentina. El análisis de la extensión e intensidad de la inmunotinción de E-cadherina y Vimentina según diagnóstico reveló una asociación estadísticamente significativa (p<0,001). Siendo la expresión de E-cadherina más alta en MON, seguido por DEO y más baja en COCE, inversamente a lo que se observó con Vimentina. El presente estudio reveló la subregulación del marcador molecular E-cadherina junto con la expresión aberrante por parte de células epiteliales del marcador mesenquimal Vimentina en muestras de MON, DEO y COCE.

The aim was to evaluate the expression of E-cadherin and Vimentin in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC), in comparison with normal oral mucosa (NOM) in a descriptive case study using immunohistochemistry. A total of fifty-one (N=51) histological samples were included; as follows: n = 16 (NOM), n = 16 (OED) and n = 19 (OSCC). All samples were analyzed using immunohistochemistry against the expression of E-cadherin and Vimentin. Immunostaining was qualitatively evaluated by extent and intensity of its expression for E-cadherin and intensity for Vimentin. Extension and intensity analysis of E-cadherin and Vimentin immunostaining according to group revealed a statistically significant association (r<0.001). E-cadherin expression was found to be highest in NOM followed by OED and lowest in OSCC, inverse to what was observed with Vimentin. The present study revealed the down regulation of the molecular marker E-cadherin, suggestive of reduction in dysplastic cells on comparison to NOM cells, and aberrant expression of the mesenchymal marker Vimentin by epithelial cells in samples of NOM, OED and OSCC; questioning their value as a prognostic marker.

Hypotrichosis with juvenile macular dystrophy: a case report with molecular study / Hipotricose com distrofia macular juvenil: relato de caso com estudo molecular

ABSTRACT Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair caused by hair follicle abnormalities as well as progressive retinal degeneration leading to blindness in the second or third decade of life. It is associated with mutations of the cadherin 3 (CDH3) gene, which result in abnormal expression of P-cadherin. Mutations in CDH3 are related to ectodermal dysplasia, ectrodactyly, and macular dystrophy. In this report, we describe an 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes. Genetic testing of the CDH3 gene revealed a homozygous gene variant at exon 6 (640A>T). This novel in-frame mutation converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.

RESUMO Hipotricose com distrofia macular juvenil (HDMJ) é uma doença autossômica recessiva rara caracterizada por rarefação capilar por alteração nos folículos pilosos e degeneracão progressiva da retina levando a cegueira na segunda e terceira década de vida. Associada a mutações no gene CDH3, resultando em expressão anormal de P-caderina. Mutações no gene CDH3 estão relacionados à displasia ectodérmica, ectrodactilia e distrofia macular. Neste relato descrevemos um menino Iraniano de 11 anos de idade, com ausência da unha na mão esquerda e rarefação capilar desde o nascimento, e que posteriormente apresentou alterações pigmentares maculares. Teste genético do gene CDH3 revelou uma variação homozigótica no exon 6 (640A>T). Essa mutação in-frame troca uma lisina por um codon de parada prematura, alterando a síntese da proteína P-caderina no cromossomo 16q22.

Progress in Diagnosis and Treatment of Hereditary Diffuse Gastric Cancer / 胃肠病学

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited disease,and may be related to the mutation of CDH1 or CTNNA1 genes.Microscopically,signet-ring cell carcinoma is suggested frequently in endoscopic biopsy or gastrectomy specimens.Some patients may have concomitant extra-stomach tumor (frequently breast cancer in females).Detection of CDH1 gene mutation should be performed in high-risk individuals,and diagnosis and treatment should be carried out by a multidisciplinary team.Prophylactic gastrectomy is recommended for those with pathogenic CDH1 mutation.Endoscopic surveillance is an option for those with CDH1 mutation of undetermined significance and those without germline CDH1 mutation.This review discussed the concept,genetic characteristics,clinicopathological features and genetic screening of HDGC for providing a reference for clinicians.

Expression of Pax2 and E-cadherin in renal cell carcinoma: correlation with clinicopathologic parameters / 中国医师杂志

Objective To investigate the expression of paired box 2 (Pax2) and E-cadherin in human renal cell carcinoma (RCC) and their correlation with clinicopathologic parameters.Methods The RCC tissue microarrays containing 85 renal cell carcinoma specimens and 35 normal kidney tissue specimens were used to detect Pax2 and E-cadherin expressions by immunohistochemistry.Results The positive expression rate of Pax2 was 77.6％ (66/85) in RCC specimens,which was significantly higher than that in 35 normal kidney tissue specimens (P ＜ 0.01).The positive expression rate of E-cadherin was 30.6％ (26/85) in RCC specimens,which was significantly lower than that in 35 normal kidney tissue specimens (P ＜ 0.01).The expression of Pax2 in RCC was significantly related to histological classification and pathological grade (P ＜ 0.05),while it was not related to the size of tumor and clinical stage (P ＞ 0.05).The expression of E-cadherin in RCC was significantly related to the size of tumor,histological classification,pathological grade and clinical stage (P ＜ 0.05).The positive expression rate of E-cadherin in survival group was significantly higher than that in death group (P ＜ 0.05).Conclusions The abnormal expressions of Pax2 and E-cadherin may play a crucial stage in development of human RCC.Detection of the expressions of Pax2 and E-cadherin can be used in the evaluation of malignant degree and prognosis of RCC.

Study on expression and correlation of Rac1 and E-cadherin protein in oral squamous cell carcinoma / 天津医药

Objective To investigate the expression levels of Rac1 and E-cadherin and their correlation in oral squamous cell carcinoma, and to explore their relations to clinical pathological parameters. Methods The expression levels of Rac1 and E-cadherin were detected in 22 samples of oral squamous cell carcinoma and 8 samples of para-carcinoma tissue by using immunohistochemistry technique (SP). The patients were divided into two groups according to the clinicopathological parameters. The differences of Rac1 and E-cadherin expression levels were analyzed between the groups. Results The positive expression rates of Rac1 were 1/8 and 77.3%(17/22) in para-carcinoma tissue and oral squamous cell carcinoma, respectively. The difference was statistically significant (P=0.003). The positive expression rates of E-cadherin were 8/8 and 31.8%(7/22), and there was a difference between them (P=0.002). The Rac1 protein expression rate was increased and E-cadherin was decreased in oral squamous cell carcinoma. There were no significant differences in Rac 1 and E-cadherin between different age and gender groups. There was significant difference in Rac1 expression between patients with metastasis and patients without metastasis (P=0.021). While there was no difference in E-cadherin expression between patients with metastasis and patients without metastasis. No correlation was found between Rac 1 and E-cadherin expressions in oral squamous cell carcinoma. Conclusion The high expression of Rac1 and low expression of E-cadherin may play an important role in the tumorigenesis and progression of oral squamous cell carcinoma.

Expression and significance of FOXC2, Vimentin and E-cadherin in colorectal adenocarcinoma / 中国医师杂志

Objective To investigate the expression of forkhead box C2 (FOXC2),Vimentin and E-cadherin protein in colorectal adenocarcinoma and the relationship of FOXC2,Vimentin and E-cadherin with the clinicopathological parameters,and the role of epithelial-mesenchymal transition (EMT) in colorec tal adenocarcinoma and the correlation between FOXC2 and EMT.Methods The expressions of FOXC2,Vimentin and E-cadherin in 102 cases of colorectal adenocarcinoma tissues and 30 cases of adjacent noncancerous tissues were detected by immunohistochemical method,and the correlation between FOXC2 and EMT and the clinicopathological parameters of colorectal adenocarcinoma were analyzed.Results The positive rates of FOXC2,Vimentin and E-cadherin in colorectal adenocarcinoma tissues were 53.9％,40.2％ and 26.5％,respectively.The positive rates of FOXC2,Vimentin and E-cadherin in adjacent noncancerous tissues were 6.7％,0 and 63.3％.Compared to paracancerous tissue,the expression of FOXC2 and Vimentin in colorectal adenocarcinoma was significantly increased,while the expression of E-cadherin was significantly decreased.The positive rates of FOXC2 and Vimentin in lymph node metastasis group were 79.1％ and 67.4％,respectively,which were significantly higher than those without lymph node metastasis (35.6％,P ＜0.01;20.3％,P ＜0.01).The positive rate of E-cadherin in lymph node metastasis group was 16.3％,which was significantly lower than that without lymph node metastasis (33.9％,P ＜ 0.01).The positive rates of FOXC2 and Vimentin in T1 +T2 phase were 41.7％ and 25.0％,respectively,which were significantly lower than those in T3 + T4 stage (83.3％,P ＜0.01;76.7％,P ＜0.01).The positive rate of Ecadherin in T1 + T2 stage group was 33.3％,which was significantly higher than that in T3 + T4 stage (10.0％,P ＜ 0.01).There was a positive correlation between FOXC2 and Vimentin in colorectal adenocarcinoma (P ＜0.01),and negatively correlated with E-cadherin expression (P ＜ 0.01).Conclusions EMT may promote the development and metastasis of colorectal adenocarcinoma,FOXC2 may be involved in colorectal cancer EMT and through the EMT to promote the malignant process of colorectal adenocarcinoma.