Positive Expression Rates Of P53 Research Articles

Expression and correlation of PBRM1 and P53 in clear cell carcinoma of kidney

Prevalence of clear cell renal cell carcinoma (ccRCC) among human population though common among adults, it occurs in children and young adults as well. The prognostic value of P53 expression in ccRCC is well known. Recently, PBRM1 has also acquired attention for its prognostic and predictive value in ccRCC. Here, we investigated the expression and correlation of PBRM1 and P53 in ccRCC. Renal tissues were collected from 70 patients who have undergone radical nephrectomy for clear cell carcinoma of the kidney in our hospital and 24 healthy volunteers for the study. We used immunohistochemical approach to determine the expression of PBRM1 and P53 in clear cell carcinoma of the kidney and normal kidney tissues and to analyze the correlation between them. Clinicopathological parameters and prognosis of patients were also studied. The positive expression rate of PBRM1 in clear renal cell carcinoma tissues was significantly higher (62.86%) compared to the normal renal tissues 8.33%. Similarly, positive expression rate of P53 in clear renal cell carcinoma tissues was 40%, while it was no expression in normal renal tissues. The expression level of PBRM1 was correlated with pathological grade and clinical stage of ccRCC patients, but not with age, sex and tumor size. P53 and expression levels were independent of age, sex, tumor size, pathological grade, and clinical stage of patients with clear cell carcinoma of the kidney. The 5-year survival rate of PBRM1 positive expression patients was 40.91% significantly lower than that of PBRM1 negative expression patients (84.62%), whereas in P53 it was 50 and 61.90%, respectively. Clinical stage, pathological grade and PBRM1 were all independent risk factors affecting the prognosis of patients with clear cell carcinoma of the kidney. Overall, the results suggest that PBRM1 is positively correlated with P53 in clear cell carcinoma of kidney (r=0.781, P=0.012). PBRM1 and P53 are both highly expressed in ccRCC and play an important role in the development of the disease. PBRM1 can also be used as an independent risk factor affecting the prognosis of ccRCC patients.

Notch Signaling in Acquired Middle Ear Cholesteatoma.

We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler™ PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 ± 32.4% and 44.9 ± 17.8%, respectively) were significantly lower than in the EAC skin (83.4 ± 17.5% and 55.7 ± 7.1%, respectively) (p < 0.001 and p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 ± 11.4%) was significantly higher than in the EAC skin (0.5 ± 0.7%) (p < 0.001). The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.

Association between TAp73, p53 and VASH1 expression in lung adenocarcinoma.

TAp73 and p53 are involved in regulating tumor angiogenesis and vasohibin-1 (VASH1) is an anti-angiogenic factor. Whether TAp73 regulates angiogenesis positively or negatively is controversial. The status of P53 may determine the effect of TAp73 on angiogenesis. To the best of our knowledge it has not been previously reported whether TAp73, p53 and VASH1 are coexpressed in lung cancer. We profiled the association between TAp73 and p53 and VASH1 expression in lung adenocarcinoma (LAC) and investigated the function of TAp73 in regulating tumor angiogenesis. TAp73, p53 and VASH1 expression in 53 human LAC tissues and the adjacent normal tissues were evaluated using immunohistochemistry. The positive expression rates of p53, TAp73 and VASH1 were significantly higher (92.6, 97.7 and 67.4%, respectively) in LAC tissue compared with paraneoplastic lung tissue (7.4, 2.3 and 32.6%, respectively, P<0.01). Pearson's correlation coefficient showed a significant positive correlation between p53 and TAp73 (r=0.474, P<0.01) and TAp73α and VASH1 (r=0.367, P<0.01). The positive expression rate of p53 and VASH1 was almost significantly correlated (r=0.187, P=0.055). Similarly, p53 expression intensity had a significant positive correlation with TAp73α (r=0.517, P<0.01) and with VASH1 (r=0.277, P<0.01), as did TAp73α with VASH1 (r=0.351, P<0.01). TAp73, p53 (mutant) and VASH1 expression was significantly higher in LAC tissue compared with paraneoplastic lung tissue. The expression trends of the three proteins were significantly positively correlated with each other in LAC. These results suggest that TAp73 may suppress tumor angiogenesis in LAC.

Expression and correlation of HPV16E6 and tumor suppressor gene p53 in oral squamous cell carcinoma

To exploring the expression of PV16E6 gene and p53 gene in patients with oral carcinoma and the correlation between pathological grade and clinical stage of oral cancer and expression of HPV16E6 gene and p53 gene. One hundred and seventy-three cases of oral cancer, 98 cases of oral precancerous lesions and 79 cases of peri-cancerous normal tissue were selected. The expression of HPV16E6 and p53 was detected by immunohistochemistry. The data were analyzed using SPSS 21.0 software package. In oral carcinoma, the expression rate of HPV16E6 was 81.5% (141/173), the expression rate of p53 was 23.7% (41/173); in oral precancerous lesions, the expression rate of HPV16E6 was 39.8% (39/98), the expression rate of p53 was 57.1% (56/98); in peri-cancerous normal tissues, the expression rate of HPV16E6 was 2.5%(2/79), the positive expression rate of p53 was 89.9%(71/79). There was significant difference in the positive expression rate of p53 and HPV16E6 among 3 groups. The expression of HPV16E6 in oral cancer was significantly higher than in the other two groups(P<0.05); the expression rate of p53 in oral cancer was significantly lower than the other two groups. In addition, with the advance of clinical stage and pathological grade, the positive expression rate of HPV16E6 increased gradually, while the positive expression rate of p53 was significantly decreased (P<0.05). HPV16E6 protein and p53 protein may play an important role in the occurrence and progress of oral cancer.

The expression of p53, p16 and Ki-67 in penile cancer and their significances

Objective To evaluate the expression of immunohistochemistry markers p53, p16 and Ki-67 in penile cancer and penile intraepithelial neoplasia (PIN). Methods 33 patients who suffered penile cancer and received organ-sparing surgery from Jan 2004 to Dec 2013 were retrospectively analysed. The expression of p53, p16 and Ki-67 were detected by EnVision/HRP two steps immunohistochemistry. Results The positive expression rates of p53 in normal penile epithelium, low-grate penile intraepithelial neoplasia, high-grate penile intraepithelial neoplasia, well-differentiated squamous cell carcinoma and poor-differentiated squamous cell carcinoma were 0, 16.7 %, 38.5 %, 30.0 % and 66.7 % respectively. The expression rates of p16 were 20.0 %, 50.0 %, 53.8 %, 70.0 % and 33.3 % respectively. The expression rates of Ki-67 were 0, 16.7 %, 61.5 %, 65.0 % and 75.0 % respectively. Conclusions The combined detection of p16 and Ki-67 can contribute to discover PIN and penile carcinoma much more earlier. p53 may be related to the occurrence and development of low differentiated squamous cell carcinoma, and p16 may be related to the occurrence and development of well-differentiated squamous cell carcinoma. Key words: Penile neoplasms; Penile intraepithelial neoplasia; p53; p16; Ki-67

Clinical Significance of CK19, CD56 and p53 in differential diagnosis of papillary thyroid microcarcinoma and thyroid papillary hyperplasia

Objective To investigate the expression and diagnostic significance of CK19, CD56 and p53 protein in papillary thyroid microcarcinoma and thyroid papillary hyperplasia. Methods The expressions of CK19、CD56 and p53 protein were detected in 52 cases of papillary thyroid microcarcinoma and 31 of thyroid papillary hyperplasia by iImmunohistochemical methods. Results The positive rate of CK19 expression was 100 % (52/52) of papillary thyroid microcarcinoma and 29.0 % (9/31) in 31 of thyroid papillary hyperplasia. There was significant difference between two groups(P<0.001). CK56 in 2 cases (3.8 %) of papillary thyroid microcarcinoma appeared mild positive expression, and in 20 cases (66.7 %) of thyroid papillary hyperplasia positive expression (P<0.001). The positive expression rates of p53 were 69.2 % (36/52) in papillary thyroid microcarcinoma and 6.5 % (2/31) in thyroid papillary hyperplasia (P<0.001). Conclusion CK19, CD56 and p53 may be important value on differential diagnosis of papillary thyroid microcarcinoma from thyroid papillary hyperplasia, and they are the indispensable markers of differential diagnosis. Key words: Papillary thyroid microcarcinoma; Thyroid papillary hyperplasia; CK19; CD56; p53

Research on expression and importance of p53, p16 and VEGF-C in cervical cancer

To investigate the expression of p53, p16(INK4A) and VEGF-C proteins in cervical cancer and their clinical importance. The expression of p53, p16(INK4A) and VEGF-C proteins in 125 cases of cervical sections were detected by two-step immunohistochemical EnVision method, and analyzed combined with the clinical and pathological data. (1) The positive expression rates of p53, p16(INK4A) and VEGF-C proteins were 56.8%, 95.2% and 88%, respectively. (2) The positive expression rate of p53 protein was 75% in lymph node metastasis-positive cases and 48.24% in lymph node metastasis-negative cases (P<0.05). The presence of difference for positive significant p53 in squamous cell carcinoma and adenocarcinoma is intensively large (P<0.01), but its expression is not much influenced by age, degree of differentiation, parametric infiltration, vascular metastasis or clinical staging (P>0.05). (3) The p16(INK4A) expression in squamous cell carcinoma is 95.65%, and it is 93.94% in adenocarcinoma, the differential expression rates bears no statistically significant, but the strong expression of squamous cell carcinoma covers 55.43% of the total number of squamous cell carcinoma, while only 15.15% rates in adenocarcinoma (P<0.01). The p16(INK4A) protein expression was not significantly correlated to age, histological type, degree of differentiation, lymph node metastasis, parametric infiltration, vascular metastasis or clinical staging (P>0.05). (4) Among the cases of lymph node metastasis, there were 100% of VEGF-C-positive expression and 82.35% of VEGF-C-negative expression, and the difference was significant (P<0.05). Among the cases of vasculature-positive samples of cervical cancer, there were 98.4% of VEGF-C-positive expression; while among the vasculature-negative samples of cervical cancer, there were 76.27% of VEGF-C-positive expression; the difference was significant (P<0.01). VEGF-C protein expression was not significantly correlated to age, histological type, degree of differentiation, parametric infiltration or clinical staging (P>0.05). The expression of some immune enzymes in cervical cancer has a reference value for early diagnosis and prognosis of cervical cancer, and has a certain guiding significance for development of the treatment program. However, a larger sample is needed for supporting the research of its significance.

Effects of Bcl-2, Bax and P53 Gene Protein Expressions in Gastric Cancer Tissue on the Apoptosis of Cancer Cells

Objective: To investigate the expression of p53 gene in gastric cancer tissue and its correlation with bcl-2 and bax protein expression in relationship and discuss the significance of their correlation in clinic. Methods: Pathological specimens from 100 gastric cancer patients with complete medical data and 24 normal lung tissue specimens were selected. Immunohistochemical streptavidin-biotin-peroxidase assay was used to detect the expression of bcl-2, bax and p53 protein. Results: p53 expression was positively correlated with bcl-2 expression (Pearson's R =0.491, P &lt;0.05). The positive expression of p53 was no significantly correlated with bax expression (P&gt; 0.05). The positive rate of p53 expression in the well-differentiated gastric cancer tissues was 17.6%, the positive rate in the differentiated tissues was 90.9%, the positive rate in the poorly differentiated tissues was 72.7%, and There was a significant difference in the expression of p53 in the three tissues (P &lt;0.05). The expression of p53 in the TNM staging showed that the positive rate in stage Iand IIwas 27.3%, the positive rate in stage III and stage IVwas 89.3%, the difference between them was significant (P &lt;0.05). Conclusions: The expression of p53 gene has an obvious clinical significance for the assessment of degree of malignancy and the prognosis of gastric cancer. Bcl-2 and p53 gene expression could jointly promote the development of gastric cancer in a synergistic way by acting on different stages of apoptosis, or bcl-2s participating in p53-induced mitochondria-mediated apoptosis signaling pathways.

Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole

To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.

Relationship of mammography, lymph node metastasis, and p53 protein expression in infiltrating ductal breast carcinoma

Objective To investigate the relationship among the mammography signs, the axillary lymph node ( LN) metastasis, and the p53 expression of infiltrating ductal breast carcinoma. Methods Mammography signs and axillary LN metastasis were analyzed in 72 cases of infiltrating ductal carcinoma. Immunohistochemistry was used to detect p53 expression in tumor specimens. The relationship among the mammography signs, the axillary LN metastasis and the p53 expression was assessed. Results The positive rate of p53 expression was 56. 7% in the patients with axillary LN metastasis, which was higher than 31.4% in the patients without axillary LN metastasis ( P ＜ 0. 05 ). The rate of axillary LN metastasis and p53 expression were 66. 7% and 70. 0% in the tumors larger than 2 cm, 56. 4% and 66. 7% in the tumors with more vascular signs, 28. 6% and 38. 1% in the tumors less than 2 cm, 30. 3% and 33. 3% in the tumors with normal vascular signs (P ＜0. 01) , respectively. The rate of axillary LN metastasis in the patients with spinulation was 70. 8% , which was higher than 41.1% of patients without spinulation (P ＜0.05). Conclusion Mammography signs of breast cancer can evaluate the axillary LN metastasis and p53 expression, and also can provide objective reference for clinical diagnosis, treatment and prognosis of breast carcinoma. Key words: Breast carcinoma; Axillary lymph node ; Metastasis; p53

Morphological features of the fimbria of the fallopian tube in pelvic serous adenocarcinoma

To study the serous lesions of the fimbria of the fallopian tube in patients with pelvic serous adenocarcinoma and investigate its significance in the serous carcinogenesis. To observe the morphological features of the fimbria of the fallopian tube in 43 cases of pelvic serous adenocarcinoma (31 cases of ovarian carcinoma and 12 cases of peritoneal carcinoma). Immunohistochemical examination of p53 expression was performed on samples of 69 fallopian tubes of 40 cases. Fimbria carcinoma was identified in 44 tubes in 31 of 43 cases. Fourteen of the carcinoma foci were ≤ 5 mm. In 68.3% of the fimbria carcinomas demonstrated involvement of the mucosa. Twenty eight tubes of 20 cases exhibited intraepithelial carcinoma. Twenty three of 44 tubes of the fibria carcinomas showed fimbria adherence and unclear appearance. The early histological changes of the fimbria epithelium included proliferation of local secretory cells, homogeneity, and straightening of the mucous folds. Clusters of tumor epithelial cells or single gland with atypical features floated between mucosal folds were found in 71.4% of the fimbria with intraepithelial carcinoma. The positive expression rate of p53 in the fimbria carcinomas and the fimbria intraepithelial carcinomas were 86.4% and 60.7%, respectively. Fimbria carcinomas is an important component in pelvic serous adenocarcinomas. The fimbria intraepithelial carcinoma is also very common among the cases of pelvic serous adenocarcinoma. The fimbria may be an important primary site of pelvic serous adenocarcinomas.

Comprehensive diagnostic value of P53, p21WAF1 and proliferating cell nuclear antigen for lung cancer

The expression of P53, p21WAF1 and proliferating cell nuclear antigen (PCNA) was detected in 114 samples of lung cancer patients (with 89 cases benign lung tissue as control) and the diagnostic value of these markers was evaluated. The results show the following: ➀ The positive expression rates of P53, p21WAF1 and PCNA in samples of lung cancer were 47.37%, 75.44% and 80.70%, respectively, which were significantly higher than that in the samples of benign lung diseases ( p < 0.001). The odds ratios were 39.15, 5.75, and 6.76, respectively. This indicates that the expression of P53, p21WAF1 and PCNA was helpful for the diagnosis of lung cancer. ➁ For the diagnosis of lung cancer, the positive likelihood ratio of P53 was 21.08, which were significantly higher than that of p21WAF1 (2.16), PCNA (2.11) and of all the combined tests. This shows that P53 expression was the most valuable for diagnosis of lung cancer. ➂ For the diagnosis of lung cancer, the negative likelihood ratio of P53/p21WAF1/PCNA parallel test was 0.057 1, which was lower than that of other single and combined tests. This indicates that P53/p21WAF1/PCNA parallel test has high diagnostic value for exclusion of lung cancer.

Prognostic significance of P-gp, GST-π and P53 expression in gallbladder carcinoma

AIM: To investigate the correlations of the expression of P-glycoprotein (P-gp), Glutathione-S-transferase-π (GST-π) and P53 with the clinicopathological features and prognosis of gallbladder carcinoma. METHODS: Forty-nine patients with gallbladder carcinoma who did not undergo chemotherapy before surgery were included in the study. The expression of P-gp, GST-π and P53 in gallbladder carcinoma was detected by immunohistochemistry. The correlations of Pgp, GST-π and P53 expression with the clinicopathological features and prognosis of gallbladder carcinoma were analyzed. RESULTS: The positive rates of P-gp, GST-π and P53 expression in gallbladder carcinoma were 75.5% (37/49), 65.3% (32/49), and 69.4% (34/49), respectively. There were positive correlations between P-gp and P53 expression and lymph node metastasis (both P＜0.05).The positive rate of GST-π expression in moderately or poorly differentiated carcinoma was higher than that in well-differentiated carcinoma (P＜0.05). The positive rate of P53 expression was significantly higher in carcinoma at Nevin stage S4-S5 (80.0%) than in that at Nevin stage S-S3 (80.0% vs 52.6%, P＜0.05). A significant correlation was also noted between the expression of P53 and P-gp in gallbladder carcinoma (r=0.343, P＜0.05). Patients with positive P-gp and GST-π expression had much lower survival rate than those with negative expression. CONCLUSION: Detection of P-gp, GST-π and P53 expression is of great significance for analyzing clinicopathological features and predicting prognosis of gallbladder carcinoma.

Expression of Gadd45a and p53 proteins in human pancreatic cancer: Potential effects on clinical outcomes

p53 gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. Gadd45a gene assumes the function to maintain the stability of genome. The present study was designed to assess the significance of Gadd45a and p53 protein expression on pancreatic cancer. The expression of p53 and Gadd45a was immunohistochemically studied in 59 patients with pancreatic cancer. The positive expression rate of p53 and Gadd45a was 67.8% and 42.4%, respectively. p53 expression in the patients <65 years was significantly higher than that in the patients >or=65 years (P=0.030). Gadd 45a expression showed no correlation to the patients' age. There was no relation for p53 expression to differentiation and TNM stages. Gadd 45a expression showed significant difference in histological differentiation (P=0.007). The median survival time of p53(+) and Gadd45a(+) group was shorter than that of p53(-) and Gadd45a(-) group (P>0.05), respectively. Meanwhile, the median survival time of p53 (+)Gadd45a(+) group was also shorter than that of p53(-)Gadd45a(-) group (P>0.05). p53 and Gadd45a proteins are both highly expressed in pancreatic cancer. The overexpression of p53 and Gadd45a may have connection with the malignant biologic behavior of pancreatic cancer.

Expression of p53R2 Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma

The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma.

Induction of pulmonary precancerous lesions by tobacco-specific NNK in Wistar rats

Tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most important carcinogen in cigarette. Models induced by NNK are widely used in investigations about the mechanisms of pulmonary neoplasia and chemoprevention studies. The aim of this study is to explore the pulmonary precancerous lesions induced by NNK and its possible mechanisms. Fifteen Wistar rats were divided into two trial groups, in which the high-dose group was instilled with iodized oil including 10 mg (50 mg/kg) NNK into the left lower lobar bronchus, and the low-dose group received 5mg ( 25mg/kg) NNK. Another 15 Wistar rats were instilled only with iodized oil as control group. All rats were examined immediately after instillation and followed up periodically by pulmogram. The pulmonary tissues of rats were pathologically examined, and the expression of AE1/AE3, PCNA and p53 was detected by immunohistochemical method. The pulmograms showed that the iodized oil localized at the bottom of left lobe and disappeared 107 days later. In trial group, 10 of 15 rats (67%) had nodus at the bottom of left lobe. All of rats in trial group (15/15) displayed atypical hyperplasia in alveolar region, showing single or multiple layers of proliferative epithelial cells along intact alveolar septa with irregular and non-discrete margins of lesion, but continuous alveolar spaces were not obliterated by proliferative epithelial cells. Ten of 15 rats in trial group showed severe atypical hyperplasia of glandular epithelium with occasional infiltrating to muscular layer. All of those atypical hyperplasia cells showed positive AE1/AE3 expression. The positive rate of PCNA was 90% (9/10) and 100% (5/5) in low-dose group and high-dose group respectively, which was significantly higher than that in control group (13%, 2/15) (P=0.000, P=0.001). The positive rate of p53 expression was 50% (5/10) and 60% (3/5) in low-dose group and high-dose group respectively, which was significantly higher than that in control group (0) (P=0.005, P=0.009). However, there was no remarkable difference in PCNA and p53 expression between low-dose group and high-dose group (P > 0.05). Transbronchial instillation of iodized oil including tobacco-specific NNK can induce pulmonary lesions as atypical hyperplasia of alveolar cell and glandular epithelium in Wistar rats. This model can be used in experimental studies about tobacco-related lung cancer.

The prognostic significance of p53, p27kip1, p21waf1, HER‐2/neu, and Ki67 proteins expression in gastric cancer: A clinicopathological and immunohistochemical study of 121 Arab patients

The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation, underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge, this is the first study from an Arab population reporting on the relationship of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 expression, and clinicopathological features and their prognostic significance. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67. The results were correlated with clinicopathological features and survival. M:F = 80:41; median age = 60 years; stage III and IV = 71%; and median follow-up = 34.4 months. Positive expression rates of p53, p27 kip1, p21 waf1, Ki67, and HER-2/neu were 54%, 40%, 8.3%, 70%, and 12% respectively. p53 expression correlated with age <60 years (P = 0.03), tumor size >5 cm (P = 0.01), p27 kip1 and Ki67 expression (P = 0.0001), and HER-2/neu (P = 0.04). p21 waf1 correlated inversely with T-stage (P = 0.008) and Her-2/neu expression correlated with histological grade (P = 0.04) and T-stage (P = 0.008). Univariate analysis showed that p53 overexpression (P = 0.01), fungating and infiltrative macroscopic appearance (P = 0.02), size >5 cm (P = 0.0001), lymph node metastasis (P = 0.0001), p T3 and T4 disease (P = 0.01), and overall stage III and IV (P = 0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (+)/p27 kip1 (-)(P = 0.02). On multivariate analysis by Cox regression model, the expression of p53 (P = 0.03) and lymph node involvement (P = 0.01) were significant adverse prognostic factors for overall survival. The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 kip1 is of added prognostic value.

Study on apoptosis of human lung adenocarcinoma cell line A549/DDP induced by ginsenoside Rh₂ in vitro

Lung cancer is one of the leading causes of cancer-related death in mankind. To exploit antitumor drug from plant has been a highlight at home and abroad. The aim of this study is to investigate the apoptosis of human lung adenocarcinoma cell line A549/DDP induced by ginsenoside Rh₂ (G-Rh₂) and to explore its possible molecular mechanism. The growth inhibition effect of G-Rh₂ on A549/DDP cells was evaluated by MTT assay. Cell cycle analysis, apoptosis index and tumor related gene expression were detected by flow cytometry. The changes of sApo-1/Fas level in the cell culture supernatant were determined by ELISA method. (1) G-Rh₂ significantly inhibited the growth of A549/DDP cells in a dose-time-de-pendent manner. (2) After 24 hours' treatment with G-Rh₂, apoptosis index of trial group was significantly higher than that of control group (P < 0.001). The proportion of cells in G0/G1 phase in trial group was much higher than that in control group (P < 0.01), while proportion in S phase in trial group was markedly lower than that in control group (P < 0.01). There was no significant difference in proportion in G2/M phase between trial group and control group (P > 0.05). (3) The positive expression rate of p53 and Fas in trial group was significantly higher than that in control group (P < 0.01, P < 0.001), while the positive expression rate of Bcl-2 in trial group was significantly lower than that in control group (P < 0.001). (4) The level of sApo-1/Fas in A549/DDP cell culture supernatant in trial group was remarkably lower than that in control group (P < 0.05). G-Rh₂ can induce the apoptosis of A549/DDP cells. Its molecular mechanism may be up-regulating expression of p53 and Fas and down-regulating expression of Bcl-2.

The Effect of Helicobacter Pylori Infection on Expression of hMSH2, hMLH1 and p53 in Gastric Carcinogenesis

Objective: To detect the expression of hMSH2, hMLH1 and p53 in gastric epithelial cells with and without Helicobacter pylori (H. pylori) infection and investigate the relationship between H. pylori infection and these genes in gastric carcinogenesis. Methods: H. pylori infection was detected by rapid urease tests. Expression of hMSH2, hMLH1and p53 in gastric cancer (GC) tissue, its adjacent mucosa, gastritic mucosa and normal mucosa was assessed by immunohistochemistry SP method. Results: Positive expression rate of hMSH2 in GC tissue (62.7%) was higher than those in adjacent mucosa (29.4%), gastritic mucosa (32.4%) and normal mucosa (30.0%) (P<0.001). Positive rate of hMSH2 in poorly differentiated adenocarcinoma (76.4%) was higher than those in other carcinomas (54.3%, 53.1%) (P<0.05). Positive expression rate of hMLH1 in GC tissue (64.3%) was lower than those in adjacent mucosa (84.4%), gastritic mucosa (82.4%) and normal mucosa (80.0%) (P<0.01). Positive rate of hMLH1 in mucoid carcinoma (43.7%) was lower than those in other carcinomas (78.2%, 64.7%) (P<0.01). Positive expression rate of p53 in GC tissue (51.9%) was higher than those in adjacent mucosa (3.1%), gastritic mucosa (0.0%) and normal mucosa (0.0%) (P<0.001). Positive rate of p53 in well differentiated adenocarcinoma (32.6%) was lower than those in other carcinomas (58.8%, 68.7%) (P<0.01). Positive rates of hMSH2 and hMLH1 in GC with H. pylori infection were lower than those without the infection, respectively (P<0.05). Positive rate of p53 in GC with H. pylori infection (61.4%) was higher than that without the infection (40.6%) (P<0.05). Conclusion: Gastric carcinogenesis may be associated with abnormal expression of hMSH2, hMLH1 and p53; H. pylori infection affecting expression of these genes may be one of its carcinogenic mechanisms.

The prognostic significance of p53, p27kip, p21waf1, Her-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study

4052 Background: The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge this is the first study from an Arab population reporting on the relationship of p53, p27kip, p21waf1, Her-2/neu, and Ki67 expression and clinicopathological parameters and their prognostic significance. Methods: Formalin fixed paraffin embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27kip, p21waf1, Her-2/neu, and Ki67. The results were correlated with clinicopathological parameters and survival. Results: M: F 80:41; median age 60 years; stage III and IV =71%; and median follow up 34.4 months. Positive expression rates of p53 (nuclear staining (NS)>10%), p27kip (NS>10%), p21waf1 (NS>10%), Ki67 (NS >25%)and Her-2/neu (membranous staining +3) were 54%, 40%, 8.3%, 70%, and 12% respectively. Using Chi square test, p53 expression correlated with age <60 years (p=0.03), tumor size >5cm (p=0.02), p27kip and Ki67 expression (p=0.001), and Her-2/neu (p=0.04). P21waf-1 correlated inversely with T stage (p=0.03). Univariate analysis (long rank test) showed that p53 overexpression (p=0.01), fungating and infiltrative macroscopic appearance (p=0.02), size >5 cm (p=0.0001), lymph node metastasis (p=0.0001), p T3 and T4 disease (p=0.01), overall stage III and IV (p=0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (-)/p27 (-)(p=0.08), p53 (+)/p27 (-)(p=0.03), and p53 (+)/p27 (+) (p=0.007) profiles. On multivariate analysis by Cox regression model, the expression of p53 (p = 0.03) and lymph node involvement (p = 0.01) were significant adverse prognostic factors for overall survival. Conclusion: The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 is of added prognostic value. No significant financial relationships to disclose.