Rate Of P53 Research Articles

Detection of p53 mutation and serum monitoring alert caused by Marek\u2019s disease virus in poultry

BackgroundMarek’s disease (MD) is a chicken neoplastic disease, which brings huge economic losses to the global poultry industry. The wild type p53, a tumor suppressor gene, plays a key role in blocking cell cycle, promoting apoptosis, and maintaining the stability of the genome. However, the mutant p53 losses its tumor inhibitory role and become an oncogene when a mutation has happened.ResultsThe mutation rate of p53 was 60% in the experimentally and naturally infected chickens. The mutations included point-mutations and deletions, and mostly located in the DNA-binding domain. The mutated p53 was expressed in various tumor tissues in an infected chicken. The mutant P53 proteins were notably accumulated in the cytoplasm due to the loss in the function of nuclear localization. Unlike the study on human cancer, the concentrations of P53 in the serums of MD infected chicken were significantly lower than the control group.ConclusionsThe p53 mutations were apparent in the development of MD. P53 and P53 antibody level in serum could be a useful marker in the diagnosis and surveillance of MD.

Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression.

Endometrial carcinoma is a common malignancy of the female genital tract. Alterations in the expression levels of various oncogenes and tumor suppressor genes serve important roles in the carcinogenesis and biological behavior of endometrial carcinoma. The aim of the present study was to evaluate the combination and individual expression of p53 and phosphatase and tensin homolog (PTEN) protein in human endometrial carcinoma. In addition, the correlation of these proteins with clinicopathological parameters was also assessed. Retrospective immunohistochemical analysis of the expression of p53 and PTEN tumor suppressor proteins was conducted in 99 women with endometrial carcinoma. The overall rate of p53 and PTEN positivity was 89 and 77%, respectively, according to the sum of stain intensity and scores of immunopositive cells. The sum of p53 positivity correlated strongly with PTEN expression (ρ=0.256; P=0.044). The concomitant sum of p53 and PTEN expression was identified in 45% of patients with endometrial adenocarcinoma. Notably, the sum of the immunohistochemical expression of p53 was significantly correlated with patient age (P=0.037), histologic type (P=0.008), histologic grade (P=0.002) and fallopian and/or ovarian invasion (P=0.014). Furthermore, PTEN expression was associated with myometrial invasion (ρ=−0.377; P=0.002) and clinical stage (P=0.019). In addition, concomitant p53 and PTEN expression was correlated with patient age (P=0.008) and histologic differentiation (P=0.028). The findings indicated a correlation between the expression of p53 and PTEN in endometrial adenocarcinoma, which suggested an intrinsic association between expression levels of these tumor suppressor genes. The study also suggested that concomitant p53 and PTEN expression contributed in characterizing the tumor behavior of endometrial carcinoma. Taken together, the present study suggested the combined expression of p53 and PTEN in the development of high-grade endometrial carcinoma in older patients. In addition, the findings indicated activation of different molecular pathways in the tumor progression between low-grade and high-grade endometrial carcinomas.

Marijuana and head and neck cancer: an epidemiological review

BackgroundMarijuana is the most widely used illicit substance in Canada. To date, no conclusive study has looked at the epidemiologic basis of marijuana use and head and neck cancer (HNC). Due to the imminent recreational legalization of marijuana in Canada, the epidemiologic relationship between marijuana use and HNC is becoming increasingly important.ObjectiveTo examine the epidemiologic characteristics of HNC patients who are recreational marijuana users.MethodsThis study was conducted at a single tertiary care centre from 2011 to 2014. Patients were enrolled consecutively at time of diagnosis of malignancy. Data was prospectively collected and included socioeconomic factors, alcohol/tobacco history, tumor characteristics, and treatment modality. Marijuana use was defined as current usage on an at least weekly basis.ResultsEight hundred seventy-nine patients met inclusion and exclusion criteria. Seventy-four (8.4%) patients were classified as marijuana users. Compared to non-users, marijuana users were less likely to be married (p = 0.048) and had less significant tobacco smoking history (p = 0.004). There were no significant differences between other socioeconomic factors or local and regional disease (p > 0.05). Marijuana users differed in the proportion of cancers stratified by primary site (p < 0.0001), with higher rates of p16+ oropharyngeal cancers, and treatment modality (p < 0.0001), with more use of chemoradiation.ConclusionsHNC patients who were marijuana users were less likely to be married and smoke tobacco. They have a distinct cancer site prevalence and are more likely to be treated by chemoradiation. Understanding the epidemiological breakdown of marijuana users amongst HNC patients will be a useful adjunct for future studies.

Can p53 expression and staining intensity correlate with histopathological prognostic parameter and clinical staging in head and neck squamous cell carcinoma?

Background: In recent years, p53 has emerged as an important tool for not only diagnosis and predicting prognosis in head and neck squamous cell carcinoma. The aim of this study was to find the role of p53 staining intensity in determining prognosis. Materials and Methods: Fifty histopathologically proven cases of squamous cell carcinoma of head and neck were studied. The findings of the study were analyzed particularly in reference to p53 expression and their correlation with age, sex, anatomical site, tumor size, histological grading, vascular, peri-neural, muscle invasion, lymph node metastasis and staining intensity.Results: Immunopositivity rate of p53 was 64% with percentage positive cells varying from 5-76% with mild, moderate and strong staining intensity. A positive correlation of p53 independently was seen with oral cavity, grade, lymph node metastasis and pathological staging.Conclusion: p53 immunoexpression is an important independent variable of prognostication.

Features of p53 expression in residual tumors in Russian women after neoadjuvant chemotherapy of breast cancer stage T1-3N0-1.

e12121 Background: Residual tumor is an important prognostic factor after neoadjuvant therapy, however, p53 expression in the residual breast tumors poorly understood. Methods: In our study included 164 Russian women (24-76, median age - 47) with breast cancer stage T1-3N0-1 treated in RCRC from 2004 to 2016. Biological subtype of primary tumor was luminal A (8,1%), luminal B HER2-negative (43,6%), luminal HER2+ (15,4%), triple negative (22,8%) and non-luminal HER2+ (10,1%). After neoadjuvant chemotherapy by anthracycline ± taxanes (in HER2+ cancer ± trastuzumab) patients had radical surgery. We analyzed pathological response after neoadjuvant therapy and features of p53 expression in residual tumors. Results: The rate of pCR was 23% for all women, and was a very various for biological type (luminal A – 0%, HER2- luminal B - 11%, HER2+ luminal - 38%, triple negative – 35% and HER2+ non-luminal - 50%), p=0,003. In 15% cases pathological response was a very similar to pCR, in 62% - was low. In analyze of 38 residual tumors we found p53 low expression (&lt;10% stained cells) in 66% cases and high (&gt;10% stained cells) - in 34%. We did not find any correlation between p53 rate in residual tumors and stage, Ki67 and PR-status (p&gt;0,05). But p53 expression strongly correlated with age, tumor grade and biological type (p&lt;0,05). So, high rate of p53 was found more often in women &lt;45 years (50%) vs women 45-59 years (15,4%) and patients 60 years older (20%), p=0,04. All G1-tumors was p53-negative, p53 high expression was seen in 29% of G2 tumors and 80% - G3, p=0,04. The high rate of p53 residual tumor was seen in luminal A subtype in 0%, HER2- luminal B – 30%, HER2+ luminal – 75%, triple negative -50%, HER2+ non-luminal - 100%, p=0,01. Conclusions: High expression of p53 in the residual tumors after neoadjuvant chemotherapy is associated with younger age and unfavorable biological characteristics that may be a very important for the further prognosis in breast cancer.

Expression of programmed death-ligand 1, topoisomerase IIα and p16 proteins in cervical cancer and their significances

Objective To analyze the expression of programmed death ligand 1 (PD-L1), p16 proteins and DNA topoisomerase Ⅱα (TOPOⅡα) in cervical cancer and their clinical significances. Methods A total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma, 30 high grade cervical intraepithelial neoplasia (CIN), 30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015. An immunohistochemical EnVision method was used to detect the expression of PD-L1, p16 and TOPOⅡα. Results The positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0% (70/106), but it was not expressed in high grade CIN, low grade CIN and normal cervical tissues, the differences were statistically significant (all P= 0.000). Whereas, in squamous cell carcinoma, the positive rate of PD-L1 in poor differentiation group [77.3% (51/66)] was higher than that in middle or high differentiation group [56.5% (21/40)], and the difference was statistically significant (χ2= 7.02,P= 0.01). According to the FIGO stage, the positive rate in stage Ⅰ-Ⅱ group [54.9% (28/51)] was lower than that in stage Ⅲ-Ⅳ group [76.4% (42/55)], and the difference was statistically significant (χ2= 5.47, P= 0.02). But there was no statistical significance in lesion size or lymph node metastasis (both P > 0.05). The positive rate of p16 in cervical squamous cell carcinoma was 99.1% (105/106), in high grade CIN was 86.7% (26/30), in low grade CIN was 26.7% (8/30), and no expression in normal cervical tissues, the differences were statistically significant (all P 0.05). The positive expression rate of TOPOⅡα in cervical squamous cell carcinoma was 97.2% (103/106), compared with that in high grade CIN [73.3% (22/30)], low grade CIN [66.7% (20/30)], and normal cervical tissues (no expression), the differences were statistically significant (all P= 0.000). But there was no significant difference in the positive expression rate of TOPO Ⅱα between high grade and low grade CIN (χ2= 0.32, P= 0.570). The expression of TOPOⅡα had no relationship with histological differentiation, FIGO stage, lesion size and lymph node metastasis (all P > 0.05). Conclusion The expression of PD-L1, p16 and TOPOⅡα is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer. Key words: Uterine cervical neoplasms; DNA topoisomerases, type Ⅱ; Programmed death ligand 1; Genes, p16

Evaluation of JC and Cytomegalo Viruses in Glioblastoma Tissue

Glioblastoma multiforme (GBM) is the most aggressive of the gliomas, a collection of tumors arising from glia in the central nervous system. Possible associations between the human cytomegalovirus (HCMV) and the JC virus with GBM are now attracting interest. Our present aim was to investigate the prevalence of the two viruses in Iranian patients from Kerman’s cities in the south of Iran. In addition, the expression rates of pp65, large T antigen and p53 proteins were assessed and their relation with GBM evaluated using reverse transcription real time PCR (rReal Time PCR). A total of 199 patients with GBM cancer were enrolled, with mean±SD ages of 50.0±19.5 and 50.7±19.6 years for males and females, respectively. The P53 rate was dramatically low suggesting an aetiological role,. Large T antigen expression was found in JC positive samples, while the PP65 antigen was observed in patients positive for CMV and JC. HCMV products and JC virus with oncogenic potential may induce the development of various tumors including glioblastomas. The JC virus produces an early gene product, T-antigen, which has the ability to associate with and functionally inactivate well-studied tumor suppressor proteins including p53 and pRB.

Quantitative analysis of nuclear shape in oral squamous cell carcinoma is useful for predicting the chemotherapeutic response.

The number of people afflicted with oral carcinoma in Japan has increased in recent years. Although preoperative neoadjuvant therapy with cisplatin and 5-fluorouracil are performed, chemotherapeutic response varies widely among the patients. With the aim of establishing novel indices to predict the therapeutic response to chemotherapy, we investigated the relationship between morphological features of pre-treatment oral carcinoma nuclei and the chemotherapeutic response using quantifying morphology of cell nuclei in pathological specimen images. We measured 4 morphological features of the nucleus of oral squamous cell carcinoma cases classified by the response to chemotherapy: No Change (NC) group, Partial Response (PR) group and Complete Response (CR) group. Furthermore, we performed immunohistochemical staining for p53 and Ki67 and calculated their positive rates in cancer tissues. Compactness and symmetry of the nucleus were significantly higher and nuclear edge response was significantly lower in cancer cells with lower chemotherapeutic responses compared high chemotherapeutic responders. As for positive rates of p53 and Ki67, there were no significant differences between any of the response groups. Morphological features of cancer cell nuclei in pathological specimens are sensitive predictive factors for the chemotherapeutic response to oral squamous cell carcinoma.

A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the growth of cancerous neural cells

Objective: There is 25–35% mutation rate of p53 in cancerous neural cells and this rate reaches 70–76% in glioma cell line. Complement of wild-type p53 has become a potential strategy for protein therapy of cancerous neural cells. Here we investigated the feasibility of a novel RDP-p53 fusion protein for anti-proliferation of cancerous neural cell and the possible mechanism, which would provide an effective approach for targeted delivery of p53 protein to treat cancerous neural cells.Methods: The RDP-p53 fusion proteins are expressed in Escherichia coli, and they are labeled with FITC and rhodamine B by chemical modification. The fluorescence-labeled proteins are added to human hepatocellular carcinoma cells (HepG-2) and human neuroblastoma cells (SH-SY5Y) in order to investigate the possibility of RDP enhancing the cell uptake efficiency into neural cells as a cell-permeable carrier. The inhibitory effect of RDP-p53 on SH-SY5Y and human glioma cells (U251) was evaluated by MTT assay. Moreover, the anti-proliferation mechanism of RDP-p53 was determined by Apoptosis and Necrosis Assay Kit and flow cytometric analysis.Results: The results showed that RDP-p53 could enter SH-SY5Y cells with high efficiency and selectively inhibit the growth of cancerous neural cells, including SH-SY5Y and U251. Also, cell apoptosis pathway and cell-cycle arrest at the G2/M phase were associated with the inhibition mechanism of RDP-p53 according to the data of flow cytometric analysis.Conclusions: RDP-p53 could be a novel antitumor candidate for targeting treatment of cancerous neural cells.

The Involvement of p53-miR-34a-CDK4 Signaling During the Development of Cervical Cancer

Aim: The aim was to explore the epigenetic mechanisms underlying cervical oncogenesis, we compared the level of microRNA-34a (miR-34a), p53, and cell cycle-related protein CDK4 within normal cervical tissue, cervical intraepithelial neoplasia III (CINIII) tissue, and cervical cancer tissue. Methods: Fresh normal cervical tissue, CINIII tissue, and cervical cancer tissue specimens were collected from patients not receiving chemotherapy, radiotherapy or immunotherapy prior to surgery. Stem-loop real-time polymerase chain reaction was employed to analyze the level of miR-34a. p53 was detected by immunohistochemistry, and cell cycle-related protein CDK4 was detected by Western blot. Results: The positive rates of p53 in CINIII and cervical cancer tissues were 35% and 68%, respectively ( P P P P Conclusion: With the progression of cervical cancer lesions, the positive rate of p53 was greatly increased which may indicate its mutation, while miR-34a was down-regulated and CDK4 was up-regulated, which suggested that all these factors might be involved in the process of cervical oncogenesis.

Relationship between HPV infection/p16 expression and radiotherapy prognosis in oropharyngeal squamous cell carcinoma

Objective To investigate the relationship between human papillomavirus (HPV) infection/p16 expression and radiotherapy prognosis in oropharyngeal squamous cell carcinoma (OSCC) and the prognostic value of p16 in OSCC patients treated with radiotherapy.Methods Tissue samples were collected from 42 patients newly diagnosed with OSCC in our hospital from January 1999 to December 2008.PCR was performed to detect HPV DNA,and p16 expression was measured by immunohistochemistry.The chi-square test was used to compare the local/regional control rate (CR) between HPV (+)/p16 (+) patients and HPV (-)/p16 (-) patients after radical radiotherapy and evaluate the association between HPV infection and p16 expression; the Kaplan-Meier method was used to calculate overall survival (OS),and the log-rank test was used for survival difference analysis.Results The follow-up rate was 100％.The HPV infection rate was 19％,and the positive rate of p16 was 43％.In patients who received radical radiotherapy,the local CR for HPV (+) patients was 100％,versus 54％ for HPV (-) patients (P =0.026) ;the local CR for p16(+) patients was 92％,versus 44％ for p16(-) patients (P =0.006) ;the locoregional CR for p16(+) patients was 69％,versus 22％ for p16(-) patients (P =0.009).For high-risk patients,HPV infection was significantly associated with p16 expression (P =0.000).The 3-year OS rates for p16(+) and p16 (-) patients were 9 1％ and 2 6 ％,respectively (P =0.001).Conclusions The p16 expression is closely associated with HPV infection in OSCC patients,and it is expected to become one of the prognostic markers in OSCC patients treated with radiotherapy. Key words: Oropharyngeal neoplasms/radiotherapy; Human papillomavirus; p16 ; Prognosis

The p53 Mutation / Deletion Profile in a Small Cohort of the Omani Population with Diffuse Large B-Cell Lymphoma

Mutations/deletions affecting the TP53 gene are considered an independent marker predicting a poor prognosis for patients with diffuse large B-cell lymphoma (DLBCL). A cohort within a genetically isolated population was investigated for p53 mutation/deletion status. Deoxyribonucleic acid (DNA) samples were extracted from 23 paraffin-embedded blocks obtained from DLBCL patients, and subjected to polymerase chain reaction (PCR) amplification and sequencing of exons 4-9 of the p53 gene. While 35% of patients analysed displayed allelic deletions (P <0.01), immunohistochemical analysis revealed a mutation rate of 69.5%. It is noteworthy that the rate of p53 mutations/deletions in this small cohort was found to be higher than that previously reported in the literature. Interestingly, patients with p53 mutations displayed a better overall survival when compared to those without. The survival of patients treated with rituximab-containing combination chemotherapy was significantly better than those who did not receive rituximab (P <0.05). Furthermore, a modelling analysis of the deleted form of p53 revealed a huge structural change affecting the DNA-binding domain. The TP53 mutation/deletion status plays a role in mechanism(s) ruling the pathogenesis of DLBCL and may be useful for stratifying patients into distinct prognostic subsets.

Abstract P3-02-04: QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway in triple-negative breast cancer

Abstract OBJECTIVES: To analyze copy number alterations(CNAs) of the genes involved in the G1/S checkpoint signaling pathway of triple-negative breast cancer (TNBC) and non- triple-negative breast cancer(non-TNBC) and in order to find specific CNAs associated with overall survive for TNBC.In all,to provide an effective target for future treatment. METHODS: We selected the samples randomly form Tianjin Cancer Hospital between August, 2006 and August, 2007,which contained one hundred TNBC cases and one hundred non-TNBC cases. Quantitative mμlti-gene fluorescence in situ hybridization (QM-FISH) was used to study CNAs of the genes involved in the G1/S checkpoint signaling pathway, including CCND1,c-Myc,p21, CHEK2, p16, Rb1, Mdm2and p53. RESULTS: The amplification rates of c-Myc and the deletion rates of p53 in TNBC tended to be higher than those in non-TNBC, whereas the amplification rates of CCND1 and Mdm2 in non-TNBC tended to be higher than those in TNBC. In Kaplan-Meier analysis, the amplification of CCND1 (P = 0.02) and c-Myc (P = 0.02) as well as the deletion of p53 (P = 0.01) predicted worse survival in the TNBC group. While in the non-TNBC group, the amplification of CCND1 (P = 0.01) and Mdm2 (P = 0.04) as well as the deletion of p53 (P = 0.049) were associated with worse survival. The amplification of c-Myc and the deletion of p53 in TNBC were associated with higher mortality risk (HR,2.87;95%CI,1.14-7.21[P = 0.03]; HR, 3.34;95%CI, 1.22-9.09 [P = 0.02]), whereas the mortality risk tended to be higher in the patients with amplification of CCND1 (HR, 4.35;95%CI,1.23-15.39 [P = 0.02])in non-TNBC. CONCLUSIONS: The amplification rates of c-Myc and deletion rates of p53 in TNBC tended to be higher than those in non-TNBC, whereas the amplification rate of CCND1 and Mdm2 tended to be higher in non-TNBC. c-Myc and p53 were independent prognostic factors for TNBC, while CCND1 was the independent prognostic factors for non-TNBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-02-04.

P16INK4a immunohistochemistry is a promising biomarker to predict the outcome of low grade cervical intraepithelial neoplasia: comparison study with HPV genotyping

ObjectiveIn cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN.Methodsp16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes.ResultsA total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively).Conclusionp16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.

Significance and expression of p53, p21(Cip1/WAF1) and Gadd45α in breast neoplasm tissues

To explore the expression and significance of p53, p21(Cip1/WAF1) and Gadd45α protein in breast cancer and their correlations with clinicopathologic features and prognosis in breast cancer. The expressions of p53, p21(Cip1/WAF1) and Gadd45α proteins were determined by immunohistochemical staining. The relationship between these three proteins and clinicopathologic features in breast cancer was analyzed by χ(2) test and Spearman's rank correlation analysis. And the survival analyses were performed with the Kaplan-Meier method and Cox regression. The differences between the curves were examined with the two-tailed Log-rank test. In 133 cases of invasive breast cancer, the positive rates of p53, p21(Cip1/WAF1) and Gadd45α protein were 58.6%, 47.4% and 41.4% respectively. The expressions of p21(Cip1/WAF1) and p53 in cancer were significantly higher than those in the adjacent mammary gland tissue (P < 0.05) while the expression of Gadd45α was lower than that in the control mammary gland tissue (P < 0.05). The positive rate of p21(Cip1/WAF1) was correlated with the histological stage, local recurrence and positive C-erbB-2. And the positive rate of Gadd45α was correlated with the histological stage, lymph node metastasis, metastasis and positive estrogen receptor/progesterone receptor (ER/PR). The positive rate of p53 was correlated with the lymph node metastasis and TNM stage. Spearman's rank correlation analysis showed that p21(Cip1/WAF1) was correlated positively with p53, p53 negatively with Gadd45α while p21(Cip1/WAF1) had no correlation with Gadd45α. With the follow-up data, Kaplan-Meier analysis showed that p21(Cip1/WAF1), Gadd45α, p53, lymph node metastasis, C-erbB-2 positive and TMN stage were associated with prognosis. Furthermore, Cox stepwise hazard analysis shows that p21(Cip1/WAF1), Gadd45α, C-erbB-2 and TMN stage were correlated with prognosis of breast cancer. Also the Kaplan-Meier analysis showed that p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) were correlated with a poor prognosis of breast cancer. The expressions of p21(Cip1/WAF1), Gadd45α and p53 are associated with the clinicopathologic features and prognosis in breast cancer. Indicating a poor prognosis of breast cancer, p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) may become independent indices for prognostic evaluations.

P53 Expression in Gastric Dysplasia and carcinoma in Erbil City

Background: Alteration in the expression of p53 tumor-suppressor protein is an event that occurs frequently in human cancer, but the practical implications of this phenomenon are yet to be fully exploited.Objectives: to determine the value of p53 expression as a marker of tumor aggressiveness and the relationship between p53 over expression and clinico-pathologic variables in gastric adenocarcinoma.Material &amp; Methods: The expression of p53 was studied immunohisto-chemically in 10 cases with gastric dysplasia and 85 cases with gastric adenocarcinomas using formalin fixed, paraffin-embedded tissue samples. D07 a monoclonal antibody to p53 protein was used for the immunehistochemical analysis. The correlation between p53 expression in gastric dysplasia, gastric adenocarcinoma and clinicopathologic variables were analyzed.Results: P53 positivity was found in 48.2% of gastric carcinoma cases, and 40% of gastric dysplasia. There was a significant correlation between the rate of p53 over expression and tumor grade (p = 0.015), and also with carcinomas associated with lymph node involvement (p = 0034). There was no significant association between p53 protein expression and histological type (p = 0.171). The association between p53 protein expression and the depth of tumour invasion was found to be statistically insignificant.Conclusion: The results obtained suggest that P53 protein expression is a useful biomarker for the assessment of gastric adenocarcinoma aggressiveness. The preoperative assessment of p53 expression in gastric carcinomas can be helpful in identifying patients with higher grades and more advanced tumors. P53 immunoreactivity can predict lymph node status in patients with gastric carcinoma.

Expression of p16 and Ki67 in cervical intraepithelial neoplasia and cervical carcinoma

Two hundred and seventy four patients with suspicious cervical lesions underwent pelvic examination and biopsy. Tissue biopsy results revealed 153 cases of cervical intraepithelial neoplasia(CIN)and 10 cases of cervical carcinoma. p16 and Ki67 were detected by immunohistochemistry method in tissue specimens. The positive rates of p16 were 9.0%, 69. 9%, 93. 8%, 95. 5% and 10/10 in normal cervical mucosa, CIN Ⅰ , CIN Ⅱ , CIN Ⅲ and cervical carcinoma, respectively; while those of Ki67 were 76. 6%,89. 2%, 91.7%, 95.5% and 10/10, respectively. The expressions of p16 and Ki67 were significantly associated with cervical lesions ( P ＜ 0. 01 ). The study suggests that p16 and Ki67 may be used as supplemental diagnostic markers for cervical lesions. Key words: Cervical intraepithelial neoplasia; Proteins

The Expression and clinical Significance of p53、p16 protein in advanced gastric carcinoma

Objective To investigate the expressions of p53,p16 protein and the clinical significance in advanced gastric carcinoma. Methods The expressions of p.53 ,p16 were detected by using immunohistochemistry in 24 specimens of normal gastric mucosa and 55 specimens of gastric carcinoma. Results The positive rate of p53 ,p16 in normal gastric mucosa and gastric carcinoma tissues were 0,100% ;67.3% ,30. 9%, respectively (P <0. 05). The positive rate of p53, p16 in non-differentiated、low- differentiated and moderate- differentiated 、high- differentiated gastric carcinoma tissues were 80. 0% ,56.7% and 48. 0% ,56. 0% ,respectively(P <0. 05). Conclusions The abnormal expressions of p53 and p16 play an important role in the course and prognosis of gastric carcinoma. The positive expression of p53 was correlated with the degree of defferentiation of gastric carcinoma. No correlation between the expression of p16 and grade of differentiation was observed. Key words: Stomach neoplasms ; Protein p53; Protein p16

Expression of P53 and MDM2protein in breast tumor

Objective To investigate the expression of anti-oncogene P53 and cancergeneMDM2 proteins and their significance inthe pathogenesis and progress of Breast tumor. Methods To detect the expression ofP53 andMDM2 in 60 cases of Breast tumor and 20 cases of normal Breast tissue with immunoh is to chemical method. Results The positive rate of P53 in the tissues of the 60 cases of breast tumor is much higher than it in the 20 cases of normal breast tissues. There is statistical significance in the disparity (P ＜ 0. 01). Mdm2, P53protein expression and tumor size was no difference (P ＞ 0. 05) , clinical stage, axillary lymph node metastasis was significant difference(P ＜ 0. 01). Conclusion Both P53 andMDM2 participate in the pathogenesis and progress of breast tumor and they can be considered as the biological index to evaluate breast tumor. Key words: P53; MDM2; Breast tunor immunohistochemistry

Dcr3 inhibit p53-dependent apoptosis in γ-irradiated lung cancer cells

Purpose: To identify genes responsible for the radiosensitivity, we investigated the role of the differential gene expression profiles by comparing radioresistant H1299 with radiosensitive H460 lung cancer cell lines.Materials and methods: mRNA profiles of lung cancer cell lines were assessed using microarray, and subsequent validation was performed with qRT-PCR (Quantitative real time-polymerase chain reaction). The expression levels of differentially expressed genes were determined by Western blot and the radioresistance of lung cancer cell lines was measured by clonogenic assay.Results: From the differentially expressed apoptosis-related genes between H1299 and H460, we found Dcr3 (Decoy receptor 3, also known as TNFRSF6B; Tumour necrosis factor receptor super family member 6B) expression was significantly (P = 4.38 × 10−7) higher in H1299 cells than H460 cells. Moreover, the Dcr3 mRNA expression level in the radioresistant cell lines (H1299, A549, DLD1, MB231, MB157) was increased in comparison to the radiosensitive cell lines (ME180, Caski, U87MG, MCF7, H460). Overexpression of Dcr3 increased the survival rate of radiosensitive H460, MCF7, and U87MG cells, and knockdown of Dcr3 abolished the radioresistance of A549 cells. The survival rate of p53 (Tumour protein 53)-deficient H1299 after gamma-irradiation was not affected by the suppression of Dcr3 expression. However, when we introduced p53 into H1299 cells, siDcr3 (siRNA of Dcr3) suppressed the radioresistance of H1299 cells by inducing p53-dependent Fas (Fas receptor, also known as TNFRSF6; Tumour necrosis factor receptor super family member 6)-mediated apoptosis pathway.Conclusion: Characterisation of gene expression profiles in two lung cancer cell lines revealed that Dcr3 expression and p53-dependent apoptosis signalling pathway regulate cellular response to ionising radiation.