Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.
Adolescent ; Adult ; Aged ; Child ; Female ; Hodgkin Disease ; Humans ; Male ; Middle Aged ; PTEN Phosphohydrolase/analysis* ; Prognosis ; Programmed Cell Death 1 Receptor/analysis* ; Retrospective Studies ; Young Adult

To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice.Xenograft model of human LSCC was established by subcutaneous transplantation of Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided into 3 groups (=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose group were injected in tumors with 20 μg of DJ-1 siRNA or 40 μg of DJ-1 siRNA in 50 μL, respectively; control group was injected with 5% glucose solution in 50 μL, twice a week for 3 weeks. The weight and size of tumors were measured before injection. The animals were sacrificed 48 h after the final treatment, and the tumors were harvested and weighed. The apoptosis and proliferation of tumor cells were determined; the expressions of Caspase-3 and Ki-67 in tumor specimens were detected with immunohistochemistry. The expression of DJ-1, PTEN, survivin mRNA and protein in tumor tissues were detected by RT-PCR and Western blotting, respectively.Tumor weight in low dose group[(0.66±0.15)g] and high dose group[(0.48±0.11)g] were significantly lower than that in control group[(0.83±0.16)g, all<0.05]. The inhibition rates of low dose group and high dose group were (20.48±0.18)% and (42.16±0.13)%, respectively. Immunohistochemistry showed that the expression of Caspase-3 was increased and Ki-67 was reduced in tumor specimens, compared with the control group (all<0.05). RT-PCR and Western blot results showed that in low dose group and high dose group the mRNA and protein expression of DJ-1 and survivin significantly decreased (all<0.05), while PTEN mRNA and protein content increased (all<0.05).High dose DJ-1 siRNA can inhibit the tumor growth in human LSCC xenograft nude mouse model, which indicates that down-regulating DJ-1 and survivin, and up-regulating PTEN expression may lead to blockage of PI3K-PKB/Akt signaling pathway and promoting tumor cell apoptosis.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Carcinoma, Squamous Cell ; chemistry ; genetics ; physiopathology ; Caspase 3 ; analysis ; drug effects ; Cell Line, Tumor ; chemistry ; drug effects ; physiology ; transplantation ; Cell Proliferation ; drug effects ; Down-Regulation ; Gene Expression Regulation ; drug effects ; genetics ; physiology ; Head and Neck Neoplasms ; chemistry ; genetics ; physiopathology ; Heterografts ; drug effects ; physiology ; Humans ; Inhibitor of Apoptosis Proteins ; analysis ; drug effects ; Ki-67 Antigen ; analysis ; drug effects ; Laryngeal Neoplasms ; chemistry ; genetics ; physiopathology ; Mice, Nude ; PTEN Phosphohydrolase ; analysis ; drug effects ; Phosphatidylinositol 3-Kinases ; drug effects ; Protein Deglycase DJ-1 ; pharmacology ; Proto-Oncogene Proteins c-akt ; drug effects ; RNA Interference ; physiology ; RNA, Messenger ; pharmacology ; RNA, Small Interfering ; physiology ; Signal Transduction ; drug effects ; genetics ; physiology

OBJECTIVE: To investigate the profile and potential significance of PTEN and NBS1 mutations among patients with familial or at early onset breast cancer in Hunan province.
 METHODS: A total of 131 breast cancer patients with familial history or suffered from breast cancer at the age of less than 35 years old were included in this study. A comprehensive phosphatase and tensin homolog (PTEN) and nibrin (NBS1) mutation analysis was performed through denaturing high performance liquid chromatography (DHPLC) and subsequent DNA direct sequencing.
 RESULTS: Among 131 patients, a reported mutation IVS4+109insTCTTA in PTEN gene were identified in two patients. The mutation frequency of IVS4+109insTCTTA was 1.15%. Two mutations in PTEN gene, 225 A>C (Thr 160 Pro) and IVS5+13T>C, was firstly discovered. Another reported missense mutation was rs121909229 G>A (Arg 130 Gln). Three mutations were detected in NBS1 gene, of which IVS6+43A>G and IVS6+127A>G were firstly discovered and another reported synonymous mutations was rs1805794 G>C (Glu 185 Gln).
 CONCLUSION The novel mutations in PTEN and NBS1 might be specific to the familial and early-onset breast cancer of Chinese Hunan population.
Adult ; Asian Continental Ancestry Group ; Breast Neoplasms ; genetics ; Cell Cycle Proteins ; genetics ; China ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Nuclear Proteins ; genetics ; PTEN Phosphohydrolase ; genetics

OBJECTIVETo investigate the expression and clinical pathological significance of EB virus (Epstein-Barr virus, EBV), PTEN and VEGF in angioimmunoblastic T -cell lymphoma (AITL).

METHODSThe EBV -encoded small RNA (EBER) expression in 21 cases of AITL was detected by in situ hybridization. The expressions of PTEN and VEGF were detected in 21 cases of AITL and 20 cases of lymph node reactive hyperplasia by immunohistochemical EnVision two-steps method. The expression and clinicopathological significance of EBV, PTEN and VEGF in AITL were analyzed.

RESULTSThe positive expression rate of EBER in 21 cases of AITL was 61.9%; the expressions of PTEN and VEGF in AITL and lymph node reactive hyperplasia were significantly different (P<0.05). The expressions of EBER and PTEN negatively correlated (P<0.05). The EBER positive expression rates of male patients in AITL group and the progressed group was 80% and 78.6% respectively, which were significantly higher than that in female patients and patients in non- advanced group (P<0.05); the PTEN expression rates in the AITL group accompanying B symptoms and progressed group were 31.3% and 21.4%, respectively, which were significantly lower than those in patients without B symptoms and non-progressed group (P<0.05). Survival analysis showed that the PTEN expression negatively correlated with the overall survival rate of patients (P<0.05).

CONCLUSIONEBV infection and low expression of PTEN may indicate the deterioration of angioimmunoblastic T-cell lymphoma. Whether the EBV involved in the ocurring of T-cell angioimmunoblastic lymphoma by down-regulating PTEN expression is unclear, further research is needed.

Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; Immunoblastic Lymphadenopathy ; In Situ Hybridization ; Lymphoma, T-Cell ; Male ; PTEN Phosphohydrolase ; Survival Analysis ; Survival Rate ; Vascular Endothelial Growth Factor A

BACKGROUNDChronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects.

METHODSQuantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis.

RESULTSRs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07-1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01-1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62-0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08-5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18-0.66). These significant effects were only evident in males after stratification.

CONCLUSIONSPTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

Carcinoma, Hepatocellular ; enzymology ; genetics ; DNA Mutational Analysis ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Liver Neoplasms ; enzymology ; genetics ; Microfilament Proteins ; genetics ; Mutation ; PTEN Phosphohydrolase ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Polymorphism, Genetic ; genetics ; Tensins

Cowden syndrome is an uncommon, autosomal dominant disease which is characterized by multiple hamartomas of the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. The diagnosis of Cowden syndrome implicates an increased risk of developing breast cancer. We report a case of a 22-year-old woman with Cowden syndrome that presented as breast cancer with concomitant bilateral exuberant benign masses in both breasts.
Arteriovenous Malformations/radiography ; Breast Neoplasms/*complications/*diagnosis/ultrasonography ; DNA/analysis ; DNA Mutational Analysis ; Diagnosis, Differential ; Female ; Hamartoma Syndrome, Multiple/*complications/*diagnosis/genetics/ultrasonography ; Humans ; PTEN Phosphohydrolase/genetics ; Thyroid Neoplasms/radiography ; Tomography, X-Ray Computed ; Young Adult

This study was aimed to investigate the expression of biomarkers (PTEN, mTOR, NF-kB, CD44, PI3K) related with bone marrow cells in patients with acute myelogenous leukemia. The immunohistochemical method was used to detect the expression of PTEN, mTOR, NF-kB, CD44, PI3K in 20 patients. The AML patients were divided into remission group and non-remission group after calculating the percentage of leukemia cells in bone marrow. The results showed that by optical microscopy, the positive expression rates of PTEN, mTOR, NF-kB, CD44 and PI3K in remission group were 33.3%, 33.3%, 77.8%, 22.2%, 0, respectively; meanwhile, in non-remission group, the positive expression rates of above-menthioned biomarkers were 63.6%, 18.2, 90.9, 63.6%, 0, respectively. The percentage and mean OD for PTEN and CD44 were statistically different between the two groups (P < 0.05), but for mTOR, NF-kB and PI3K were not statistically differenly (P > 0.05). It is concluded that the high expression of PTEN and CD44 can be regarded as an important index for diagnosis and prognosis in acute myelogenous leukemia.
Biomarkers ; analysis ; Bone Marrow Cells ; chemistry ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; NF-kappa B ; PTEN Phosphohydrolase ; Phosphatidylinositol 3-Kinases ; Prognosis ; TOR Serine-Threonine Kinases

Adaptor Proteins, Signal Transducing ; analysis ; Apoptosis ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; analysis ; Male ; Neoplasm Proteins ; analysis ; PTEN Phosphohydrolase ; analysis ; Retinal Neoplasms ; drug therapy ; Retinoblastoma ; drug therapy ; Topoisomerase I Inhibitors ; pharmacology ; Topotecan ; pharmacology

Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; Carcinoma, Papillary/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Exons ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; PTEN Phosphohydrolase/metabolism ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Republic of Korea ; S100 Proteins/metabolism ; Thyroid Neoplasms/genetics/metabolism/*pathology ; Tumor Markers, Biological/metabolism ; Young Adult

BACKGROUNDRetinocytoma (RB) is a very common intraocular malignant tumor during infancy. Chemotherapy has gradually been used as the first-line treatment for intraocular RB in recent years. In this study, Livin and PTEN expressions were observed in the RB tissue, along with the growth-inhibiting and apoptosis-induced effects of topotecan (TPT) on RB HXO-Rb44 cell strain. This study aimed to investigate the antigrowth effects of TPT on RB cell strain HXO-Rb44.

METHODSMax-Vision(TM) rapid immunohistochemistry was adopted to detect Livin and PTEN expressions in the normal retina and in RB, and their relationship with RB clinicopathologic features was analyzed. Human RB cell strain HXO-Rb44 was cultivated and passaged. MTT method was used to measure the survival rates of HXO-Rb44 cell strains under various TPT concentrations. IC50 values were calculated. Flow cytometry was used to detect the effects of various TPT concentrations on HXO-Rb44 cell apoptosis. Western blotting was used to detect the differences of Livin and PTEN protein expressions during cell apoptosis.

RESULTSThe positive expressions of Livin and PTEN in the RB group were obviously different from those in the normal control group. In RB tissue, Livin expression was relevant to PTEN expression. TPT could significantly induce the occurrence of cell apoptosis and had a dependent relationship with drug concentration. Livin and PTEN expression levels varied with the extension of the effect time of TPT based on Western blotting analysis.

CONCLUSIONSLivin and PTEN have high and low expression levels in the RB tissue, respectively. Both of them have key roles in RB occurrence and development. TPT could induce human RB cell strain HXO-Rb44 cell apoptosis, and its mechanism is associated with the inhibition of Livin and PTEN expressions.

Adaptor Proteins, Signal Transducing ; analysis ; Apoptosis ; drug effects ; Cell Line, Tumor ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Infant ; Inhibitor of Apoptosis Proteins ; analysis ; Male ; Neoplasm Proteins ; analysis ; PTEN Phosphohydrolase ; analysis ; Retinal Neoplasms ; drug therapy ; pathology ; Retinoblastoma ; drug therapy ; pathology ; Topoisomerase I Inhibitors ; pharmacology ; Topotecan ; pharmacology