Pediatric inherited cancer predisposition syndromes and TP53 germ-line mutation / 临床儿科杂志

Pediatric inherited cancer predisposition syndromes are a group of diseases caused by germ-line mutation of cancer related genes. The patients are susceptible to cancers. TP53 germ-line mutation is the most commonly seen mutant gene in cancers that accounts for 20%-30%of all germ-line mutations of inherited cancers. TP53 gene mutation screening could help clinicians to better manage the patients and their family members.

Patterns and Biologic Features of p53 Mutation Types in Korean Breast Cancer Patients / 한국유방암학회지

PURPOSE: The p53 gene is one of the most frequently mutated genes in breast cancer. We investigated the patterns and biologic features of p53 gene mutation and evaluated their clinical significance in Korean breast cancer patients. METHODS: Patients who underwent p53 gene sequencing were included. Mutational analysis of exon 5 to exon 9 of the p53 gene was carried out using polymerase chain reaction-denaturing high performance liquid chromatography and direct sequencing. RESULTS: A total of 497 patients were eligible for the present study and p53 gene mutations were detected in 71 cases (14.3%). Mutation of p53 was significantly associated with histologic grading (p<0.001), estrogen receptor and progesterone receptor status (p<0.001), HER2 status (p<0.001), Ki-67 (p=0.028), and tumor size (p=0.004). The most frequent location of p53 mutations was exon 7 and missense mutation was the most common type of mutation. Compared with patients without mutation, there was a statistically significant difference in relapse-free survival of patients with p53 gene mutation and missense mutation (p=0.020, p=0.006, respectively). Only p53 missense mutation was an independent prognostic factor for relapse-free survival in multivariate analysis, with an adjusted hazard ratio of 2.29 (95% confidence interval, 1.08-4.89, p=0.031). CONCLUSION: Mutation of the p53 gene was associated with more aggressive clinicopathologic characteristics and p53 missense mutation was an independent negative prognostic factor in Korean breast cancer patients.

Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

PURPOSE: The fibroblast growth factor receptor 3 (FGFR3) gene is known to be frequently mutated in noninvasive urothelial carcinomas of the bladder. In this study, we investigated the expression of FGFR3, Ki-67, and p53 in bladder cancers and the effects of expression on tumor recurrence. MATERIALS AND METHODS: Fifty-five cases of primary bladder cancer were examined by immunohistochemistry. The relationship of these markers with various clinicopathological factors, including recurrence, was assessed. RESULTS: Positivity for cytoplasmic FGFR3 (FGFR3-c) was associated with a lower cancer grade (p=0.022) and stage (p=0.011). Recurrence was more frequent in patients with a higher stage, negative FGFR3-c, and high Ki-67 expression. According to univariate analysis, predictors of recurrence-free survival included the following: age, stage, FGFR-c, Ki-67, and p53. However, none of these was independent from the other parameters in multivariate studies. CONCLUSIONS: The immunohistochemical expression of FGFR3 is not only one of the characteristic features of lower-grade and lower-stage urothelial carcinoma but also a possible marker in predicting disease recurrence.

Clinical Implications of the Expression of Survivin and p53 in Superficial Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

PURPOSE: The prognostic value of p53 remains controversial in transitional cell carcinomas of the bladder. Survivin, an inhibitor of apoptosis, is expressed in many human cancers. Recent studies have reported increased expression of survivin in superficial transitional cell carcinomas of the bladder. We investigated the expression of survivin and p53 and the clinical implications of this expression in superficial transitional cell carcinomas of the bladder. MATERIALS AND METHODS: Immunohistochemical staining of paraffin sections using a monoclonal antibody for survivin and p53 was performed in 82 cases of superficial transitional cell carcinomas of the bladder. Correlations between the expression of survivin and p53 and clinicopathological features, such as age, multiplicity of tumor, size, recurrence, and progression, were examined. RESULTS: Among 82 cases, positive survivin expression (greater than 20%) was observed in 59 cases. Positive p53 expression (greater than 20%) was observed in 46 cases. There were no significant differences in age, gender, multiplicity, tumor size, tumor grade, pT stage, recurrence, or progression-free survival between p53-positive and p53-negative groups (p>0.05). Also, there were no significant differences in age, gender, multiplicity, tumor size, tumor grade, or pT stage between survivin-positive and survivin-negative groups (p>0.05). However, recurrent-free and progression-free survivals were significantly lower in the survivin-positive group than in the survivin-negative group (p<0.05). CONCLUSIONS: The expression of survivin can be recommended as a useful marker for predicting disease recurrence and progression. Survivin may be superior to p53 as a prognostic factor in superficial transitional cell carcinoma of bladder.

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkins disease

CONTEXT AND OBJECTIVE: Tumor cells in Hodgkins disease (HD) express cell proliferation markers that are evaluated according to the oncogenes involved or the expression of their proteins. Correlations between the protein expression grade and clinical data are now important for disease prognosis. DESIGN AND SETTING: This was a retrospective analysis on proliferating cell nuclear antigen (PCNA), p53 and MDM2 (murine double minute-2) expression using immunohistochemistry, on formalin-fixed, paraffin-embedded tissues from diagnostic biopsies on 51 patients with HD. The study was conducted at the Division of Hematology and Transfusion Medicine, Hospital São Paulo, Universidade Federal de São Paulo. METHODS: Antigen expression was evaluated as the proportions of positive Hodgkin and Reed-Sternberg (HRS) cells and reactive lymphocytes (L), which were compared using Spearman correlation coefficients. The Friedman test was used for comparisons between the markers. The Pearson test was used to investigate associations between marker expression and clinical and laboratory parameters, marrow involvement, complete remission (CR) and overall survival (OS) rates. RESULTS: There was overexpression of antigen proteins in HRS, in relation to L (p < 0.001). In HRS, MDM2 was higher than p53 and PCNA (p < 0.003), while the latter two were equivalent. In L, p53 was lower than MDM2 and PCNA (p < 0.001), while the latter two were equivalent. There was no relationship between protein expression and clinical and laboratory variables or outcome. CONCLUSIONS: PCNA, p53 and MDM2 are tumor markers for HD, but showed no clinical or prognostic significance in our analysis.

CONTEXTO E OBJETIVO: As células tumorais da doença de Hodgkin (HD) são positivas para marcadores de proliferação celular que são analisados por seus genes e respectivas proteínas. A correlação entre a expressão destas proteínas e os parâmetros clínico-laboratoriais são, no momento, de importância para o prognóstico da doença. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo da expressão do antígeno de proliferação celular (PCNA) e da p53 e MDM2 em tecidos obtidos ao diagnóstico, fixados por formol, embebidos em parafina de 51 pacientes com HD. O trabalho foi realizado na Divisão de Hematologia e Transfusão, Hospital São Paulo, Universidade Federal de São Paulo. MÉTODOS: As expressões antigênicas foram analisadas através da proporção de células de Hodgkin e células de Reed Sternberg (HRS) e linfócitos reacionais (L) positivos. A intensidade de expressão de cada proteína foi comparada entre L e HRS através do coeficiente de Spearman. A comparação da PCNA, p53 e MDM2 em L e HRS se fez pelo teste de Fiedman. As correlações entre variáveis clínico-laboratoriais, comprometimento da medula óssea, taxas de sobrevida geral e remissão clínica com as proteínas em HRS se fizeram pelo coeficiente de Pearson. RESULTADOS: Houve superexpressão das três proteínas em células HRS comparadas aos L (p < 0,001). Nas células HRS, a MDM2 foi maior que a p53 e a PCNA (p < 0,003), que foram equivalentes. Nos L, a p53 foi menor que a MDM2 e a PCNA (p < 0,001), que foram equivalentes Não houve relação entre as expressões das proteínas com as variáveis clínico-laboratoriais e sobrevida. CONCLUSÕES: PCNA, p53 e MDM2 são marcadores tumorais na HD, porém não mostraram significado clínico-prognóstico em nossa análise.

Prognostic Value of Cyclooxygenase-2 and p53 Expression in Stage T1 Grade III Bladder Cancer / 대한비뇨기과학회지

Purpose: The prognostic value of p53 remains controversial in stage T1, grade III (T1GIII) transitional cell carcinomas (TCC) of the bladder. Recent studies have reported increased expression of cyclooxygenase-2 (COX-2) in bladder cancer. The prognostic values of p53 and COX-2 were compared in T1GIII TCC of the bladder. Materials and Methods: Among 57 consecutive patients, diagnosed with T1GIII TCC of the bladder by transurethral resection (TURB), 37 were eligible for this study. Exclusion criteria included; the first TURB performed elsewhere, no or inadequate (less than 6 weeks) bacillus Calmette- Guerin treatment and postoperative follow-up of less than 1 year. The expressions of p53 and COX-2 were evaluated by immunohistochemical staining of TURB tissues. Possible correlations of the p53 and COX-2 expressions with the clinicopathological features, such as age, shape and multiplicity of tumor, recurrence and progression, were examined. Results: During a mean follow-up of 27 months, the disease recurred in 43.2% and progressed in 16.2%. Of the 37 specimens, 31 (83.8%) and 16 (43.2%) stained positive for COX-2 and p53 expressions, respectively. There were no significant differences in age, shape and multiplicity of the tumors, recurrence-free survival and progression-free survival between the p53 positive and negative groups. However, the recurrence-free and progression-free survivals were significantly lower in the COX-2 positive than in the COX-2 negative group (p=0.049 and p=0.027, respectively). When combined, p53 and COX-2 more accurately predicted recurrence than COX-2 alone (p=0.036), but not the progression (p=0.776). Conclusions: In the pathologically homogeneous group of T1GIII TCC of the bladder, COX-2 was superior to p53 in predicting the prognosis.

Clinical Significance of p16 Protein Expression Loss and Aberrant p53 Protein Expression in Pancreatic Cancer

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.

Human Papillomavirus Type 16, 18, and 33 Infection in Adenocarcinoma of the Uterine Cervix: Analysis of the p53 Gene Mutation and the Clincopathologic Correlation

BACKGROUND: Current evidence implicates specific types of the human papillomavirus (HPV) are involved in the development of cervical cancer. In HPV-negative cervical carcinomas, p53 mutation is thought to be a mechanism of oncogenesis. The purpose of this study was to evaluate the prevalence of p53 mutations in cervical adenocarcinomas and to investigate their correlation with HPV status and clinicopathologic parameters. METHODS: A series of 38 primary cervical adenocarcinomas was analyzed for both HPV infection and p53 mutations. The HPV 16, 18, and 33 status was investigated by PCR amplification. The point mutations of the p53 gene were detected by the PCR-SSCP technique. RESULTS: The prevalence of HPV 16, 18, or 33 infection was 73.7% (28/38). HPV 16 was present in 12 cases, HPV 18 was present in 15 cases, and HPV 33 was positive in one case. There was only one case that was positive for 18 as well as a p53 mutation in exon 6. CONCLUSIONS: Our results indicate that HPV 18 infection was more common in cervical adenocarcinomas than HPV 16 infection. Mutant p53 was rarely found in cervical adenocarcinomas regardless of the type of HPV infection. There was no correlation between HPV infection and clinical stage or pathologic type of tumor.

Expression of p53 and p73 Genes in Human Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

PURPOSE: We analyzed the tissue samples of bladder transitional cell carcinoma (TCCa) for both the p53 and p73 gene, and we attempted to elucidate their possible roles in the pathogenesis of bladder TCCa. MATERIALS AND METHODS: After homogenizing 33 samples of bladder TCCa and 3 normal bladder tissues, the genomic DNA was isolated for PCR. The primers used for PCR were exon 5-10 for p53 and exon 8 and 13 for p73. The mutation analysis was performed by an automatic sequencing analyzer. The results were compared to the grade and stage of the bladder cancers. RESULTS: Mutations of p53 and p73 were noted in 18 (54.5%) and 19 samples (57.6%), respectively, out of 33 bladder cancer tissue samples. The frequency of p53 mutation were significantly higher for invasive and high grade cancer (p=0.04). Mutation of p73 show no statistically significant difference according to invasiveness (p=0.224); however, it show a significantly higher incidence in high grade cancer (p=0.026). Simultaneous mutations of p53 and p73 show a significant increase in higher grade cancer (p=0.025) and in the higher cancer stages (p=0.045). Recurrence-free probabilities for patients with superficial bladder cancer were significantly correlated with the p53 and p73 mutation. CONCLUSIONS: Mutation of p73, as well as p53, which is already known as a predictor for the recurrence and progression of bladder cancer, also seems to be related to the pathogenesis and prognostic factors of TCCa of the bladder.

A study on p53 and Rb genes in gastric cancer and juxta-cancerous tissue / 第三军医大学学报

The deletion and rearrangement of p53 and Rb genes were studied in gastric cancer with Southern blot hybridization and the point mutation in 248 and 249 codons of p53 was studied with PCR-RFLP.It was found that deletion or rearrangement of p53 was seen in 9 cases out of 30 cases of gastric cancer and point mutation at 248 codon of p53 in 2 cases out of 42 cases,and deletion and rearrangement of Rb gene were seen in 2 cases out of 15 cases.