Positive Expression Of P53 Protein Research Articles

Evaluation of Immunohistochemical Expression of P53 and Pcna in Pleomorphic Adenoma, Mucoepidermoid and Adenoid Cystic Carcinomas of Salivary Glands

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepider moid carcinoma and adenoid cystic carcinoma predominate among the malignancies. The aim of this study was to describe the tissue expression of p53 and PCNA protein in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma and to compare their expression among the studied tumors. The study enrolled (45)formalin –fixed, paraffin- embedded tissue blocks of salivary gland tumors, diagnosed as pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma (15 cases for each ) and evaluated the immunohistochemical expression of P53 and PCNA proteins. The study revealed positive p53 protein expression in (60%) of muocoepidermoid carcinoma cases and (20%) of adenoid cystic carcinoma cases, while only one case (6.7%) of pleomorphic adenoma was P53 posi tive. The immunopositivity of PCNA protein expression was f ound in (100%) of both mucoepidermoid carcinoma and adenoid cystic carcinoma cases and (66.7%) of pleomorphic adenoma c ases.The results of this study demonstrated that inactivation of p53 protein may play an im portant role in the activation of PCNA with increasing the proliferati on activity of MEC and ACC.

The High Expression of p53 Is Predictive of Poor Survival Rather TP53 Mutation in Esophageal Squamous Cell Carcinoma.

TP53 is a well-known tumor suppressor gene and one of the most common genetic alterations in human cancers. However, the role of p53 as a prognostic marker of esophageal squamous cell carcinoma (ESCC) is controversial in the association between TP53 alterations and clinical outcomes. To address this issue, we evaluated TP53 mutations, p53 protein expression, clinicopathological parameters, and survivals rates in a large scale of patients with ESCC. Two cohorts were included in this study: TP53 mutations were detected by next-generation sequencing in 316 ESCC patients, and p53 protein expression was tested by immunohistochemistry in 6,028 ESCC patients. Survival analysis was performed using the Kaplan-Meier curve and the Cox proportional hazards model. TP53 mutations were found in ESCC patients from 241 of 316 (76.3%), and the rate of positive expression of p53 protein was 59.1% in 6,028 ESCC patients (including 1819 with high expression of p53 protein), respectively. Most mutations were missense, which has a high expression of p53 protein. Compared with wild-typeTP53, TP53 gene mutations were not significantly associated with survival time (p=0.083). In multivariate analysis, the p53 protein expression was an independent prognostic factor for ESCC. The high-expression group of p53 protein has poor survival (p < 0.001) compared to low-expression group in patients with ESCC. The high expression of the p53 protein, not the TP53 mutation, is predictive of poor survival in patients with ESCC, and p53 protein expression might have the potential to be a prognosis biomarker and therapy target in ESCC.

Association of Protein Expression p53 Mutants with Regional Lymph Gland Status on type III Carcinoma Nasofaring Patients.

Nasopharyngeal carcinoma (NPC) is a malignant disease originating from the nasopharyngeal epithelial cells. The molecular mechanism of cancer occurrence is a change in the oncogene and tumor suppressor genes. One of the tumor suppressor genes that mutate in cancer cells is the mutant p53 gene. One of nasopharyngeal carcinoma progression is determined by the status of regional lymph gland. The enormous regional lymph node has a poor prognosis. To analyze the expression of the mutant p53 protein in Nasopharyngeal carcinoma (NPC) that correlated with regional lymph gland status (N) as a clinical manifestation. Expression of mutant p53 protein from NPC tissue paraffin block with immunohistochemical cracking technique was using monoclonal rabbit Anti Human p53 clone 318-6-11 (Dako, North America, Inc., 6392 Via Real Carpinteria, CA 93013 USA), microscope light binoculars was assessed visually by an Anatomical Pathology Consultant. Positive expression of p53 mutants was obtained 57.58% from all the sample in N0 by 0 subjects, N1 was 6 subjects, N2 was 7 subjects, and N3 was 7 subjects. The results of Mann-Whitney U test was p = 0.706, then there was no significant (p > 0.05) correlation between positive expression of p53 protein in type III WHO NPC with the regional lymph gland were N0, N1, N2, and N3. There was no significant between expression protein p53 mutants' regional and lymph gland in type III WHO NPC.

P53 protein expression in HER2-negative breast invasive ductal carcinoma

To determine the expression of p53 and its clinical significance in HER2-negative breast invasive ductal carcinoma (BIDC). The expression of p53, ER and PR in the HER2-negative BIDC was detected by immunohistochemistry and the results were analyzed by SPSS10.0 software packet, chi-square test, spearman's correlation analysis, Kaplan-Meier survival curves and Cox regression analysis. The positive expression of p53 protein in BIDC with pathological grade III was significantly higher than that with grade I (P<0.05), but there was no significant correlation between the expression of p53 and age, clinical stage, or lymph node metastasis status in the BIDC. The positive expression of p53 protein in BIDC with ER-positive was significantly lower than that with ER-negative (P<0.01). The positive expression of p53 protein was significantly lower in BIDC with common expression of ER and PR than that with negative expression of ER or PR (P<0.05). The HER2-negative BIDC patients with p53-positive expression had a lower 5 year survival than those with p53-negative expression. The positive expression of p53 protein might have significant prognostic value and is an independent prognostic marker in HER2 -negative BIDC.

Immunohitochemical study of p53 protein expression in gastroesophageal reflux disease

ObjectiveThis study aimed to determine p53 protein expression by immunohistochemistry in the esophageal mucosa of patients with gastroesophageal reflux disease (GERD).BackgroundGERD is a common clinical disorder that can significantly impact the patient's quality of life and pose a significant burden on healthcare systems worldwide. The incidence of esophageal adenocarcinoma has been increasing rapidly over the past few decades. The major risk factors predisposing to the development of adenocarcinoma are long-standing GERD and Barrett's esophagus. P53 protein expression in esophageal carcinogenesis is still being studied. The identification of tumor markers in patients with GERD may enable recognition of subgroups of patients who are more at risk of developing dysplasia and/or cancer.Patients and methodsThis study was carried out on 200 patients with symptoms of GERD. They were recruited from the endoscopy unit of Menoufia University Hospital between August 2010 and March 2013, and were included in group 1. According to the results of upper endoscopy and histopathology, they were subdivided as follows: group 1a included patients with GERD with erosive esophagitis ( n = 180), group 1b included patients with GERD and Barrett's esophagus ( n = 20), and group 2 included 20 patients with other GIT symptoms with no reflux and normal esophageal squamous epithelium; this was the control group. Written valid consent was obtained from every patient for examination and upper endoscopy; the clinical sheet for every case was completed, including assessment of history, examination, and the investigations required.ResultsWe found negative reactivity for p53 in 20 histologically normal patients (0%), and positive p53 protein expression in 76 patients (40%) in the esophagitis group and in 14 patients (70%) with Barrett's metaplasia ( n = 20). According to the Los Angeles classification grade, p53 was overexpressed in 33.3% ( n = 24) of esophagitis grade A (mild esophagitis) patients, 46.3% ( n = 32) of esophagitis grade B (moderate esophagitis) patients, 56.4% ( n = 22) of esophagitis grade C patients, and 60% ( n = 12) of esophagitis grade D (severe esophagitis) patients.ConclusionGERD grades C and D were more prevalent in Barrett's esophagus. P53 expression was higher in Barrett's esophagus than in erosive esophagitis compared with the normal group. P53 protein expression increases gradually with the severity of esophagitis caused by GERD.

Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma

BackgroundCodon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.Materials and methodsIn total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan–Meier method, and log-rank test.ResultsThe p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092–0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032).ConclusionsThe p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.

The expression of BRCA1, P53, KAI1, and Nm23 in ovaries of BRCA1 mutation carriers after prophylactic adnexectomy

IntroductionHigh mortality rate, absence of reliable methods for early diagnosis and poor prognosis of advanced ovarian cancer prompted to investigate the role of prophylactic oophorectomy in BRCA1 mutation carriers as well as evaluate the expression of BRCA1, p53, Nm23, and KAI1 proteins in ovarian tissue from these patients.Materials and methodsOvaries from BRCA1 mutation carriers underwent prophylactic adnexectomy and control group of patients were operated from other than cancer reasons. The expression of selected proteins was studied using immunohistochemical staining. The intensity of immunostaining and the number of tumor cells showing the reaction for selected proteins were analyzed.ResultsWe have analyzed ovarian tissues from 18 BRCA1 mutation carriers and 11 women included in control group. Positive expression of BRCA1 protein was presented in 83.3 % cases in BRCA1 mutation carriers and in 72.7 % in the control group (p > 0.05). Positive expression of p53 protein was observed, respectively, in 27.8 vs. 36.4 % (p > 0.05), Nm23 protein 77.7 vs. 90.9 % (p > 0.05), and KAI1 in 72.2 vs. 72.7 % (p > 0.05). Mean percent of tumor cells that showed the reaction for selected proteins as well as the intensity of immunostaining for all analyzed proteins seems to be lower in BRCA1 mutation carriers.ConclusionsHowever, any significant differences between study group and control group have not been found; there were similar trends showing reduced expression of studied proteins in BRCA1 mutation carriers.

Patterns of recurrence and prognostic factors of disease free survival in penile squamous cell carcinoma treated with lymphadenectomy

Objective To evaluate the recurrence patterns and possible prognostic factors in primary penile cancer treated with penectomy and standard lymphadenectomy.Methods The records of 73 patients with penile squamous cell carcinoma who underwent penile amputation and regional lymphadenectomy between 1990 and 2005 were reviewed.The median follow up was 32 ( 16 - 183) months.Molecular markers including p53 and Ki-67 were detected using immunohistochemistry.Recurrence patterns,pathological characteristics,and patient outcomes were analyzed.Results Twenty( 27.4％ ) patients developed recurrences at a mean of 11 (6 - 17 ) months postoperatively and 3 cases remained alive at last follow-up.The mean cancer specific survival of the recurrent patients was 26 ( 16 - 83 ) months.Distant metastasis and multiple recurrences were common among patients with high-grade tumor (P =0.017 ).Univariate analysis revealed that higher primary tumor stage,higher pathological grade,lymph node metastasis,extra-nodal involvement and positive p53 protein expression were significantly associated with decreased 3-year disease free survival rates.Cox regression identified that only pathological grade ( P =0.025 ) and lymph node status ( P =0.024 ) were independent predictors of disease free survival.Conclusions Pathological grade and lymph node status were independent predictors of disease free survival in patients with penile squamous cell carcinoma in this cohort.Patients with high-grade disease are likely to recur in a distant or multiple pattern. Key words: Penile neoplasms ; Carcinoma; Lymph node excision ; Prognosis ; Disease-freesurvival

Lymphocyte subpopulations in peripheral blood of breast cancer patients

s / The Breast 20 (2011) S12–S55 S25 Results: Similarly, association between p53 protein and disease response was evaluated. With 90% confidence it was established, that p53 protein overexpression influences disease progression (Fisher‘s p 1⁄4 0.096). Wealso estimated the impactof proteinexpressionondisease outcomes in 24 patients who underwent only first-line treatment against metastatic breast cancer. If p53 protein overexpression was found, mean survival was 28.5 months (SEM1⁄4 5.4, 95% CI 17.9–39.0) andmedian 25months (SEM1⁄4 6.9, 95% CI 11.4–38.6), if itwasabsent– survivalwas slightly longer:mean33.6months (SEM1⁄4 4.2, 95%CI 25.3–41.8) andmedian 30months (SEM1⁄4 2.6, 95%CI 24.9– 35.0). Kaplan-Meiermethod did not detect statistically significant differences between the groups (log-rank p > 0.05, Breslow p > 0.05). For small samples, associations among molecular markers were evaluated using Fisher‘s exact test. It was established, that p53 protein has a trend to be associated with underexpression of ER (OR1⁄4 5.83, 95% CI 0.9–37.81, p1⁄4 0.064). Associations among other factors were non-significant. Analysis of combinations of ER and PR (ER-PR-, ER-PR+, ER+PR-, ER+PR+) with p53 protein and HER2 was also conducted. However, there were no significant association between them. Additionally, combination of negative expression in 3 markers (ER, PR and HER2) with p53 protein expressionwas checked. Thus, significant associationwas found between positive p53 protein expression and combination of molecular markers ER-PRHER2(Fisher‘s p 1⁄4 0.041). Conclusion: It was established, that combination of molecular markers ER-PR-HER2is 7.7 times (95% CI 1.16–51.17; p 1⁄4 0.035) more likely in case of positive expression of p53 protein and it is associated with the worse prognosis of the patients.

Loss of p53 in esophageal squamous cell carcinoma and the correlation with survival: Analyses of gene mutations, protein expression, and loss of heterozygosity in Japanese patients

A high frequency of p53 protein expression or gene mutation has been reported in the early stages of esophageal squamous cell carcinoma (ESCC), and thus loss of p53 function is thought to be very important in esophageal carcinogenesis. However, there is controversy surrounding the correlation between p53 dysfunction and ESCC tumor progression. The complexity arises from the different modalities, such as mutation analysis, immunohistochemistry, and the detection of loss of heterozygosity (LOH) at the p53 genomic locus. In this study, we comprehensively analyzed p53 gene mutation, p53 protein expression, and LOH at 17p13 in 94 surgically resected Japanese cases of ESCC. The frequency of p53 gene mutation was 60.6%. The rate of positive p53 protein expression was 56.4%. The frequency of LOH at 17p13 was 67.5%. There was a statistically significant correlation between the presence of a gene mutation and LOH, whereas, there was no significant correlation between gene mutation and protein expression. Despite the importance of loss of p53 function in esophageal carcinogenesis, none of the examined parameters, either singly or combined, correlated with overall survival. Taken together, p53 function is a primary target for esophageal carcinogenesis but there is no apparent correlation with the malignant phenotype in ESCC.

Abnormal expression of c-myc, p53, p16 protein and GNAS1 gene mutation in fibrous dysplasia

To study the significance of c-myc, p53 and p16 protein expression in fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to explore the property of fibrous dysplasia. The expression of c-myc, p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20 control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia. C-myc protein immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with the negative control group, the difference was significant. P16 positive was detected in 34 FD cases (P = 0.001). The difference was significant as compared with the positive control group. Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation. PCR amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud syndrome, 1 case was a monostotic lesion. C-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD. The abnormal expression of the gene p16 might play an important role in the formation of FD. The GNAS1 mutation exist in FD. All of the results indicate that FD could be a neoplasia disease, caused by multiple factors leading to a dysfunction of bone development.

Boron neutron capture therapy inducing apoptosis in U87 glioblastoma cells

Objective To explore the effect of boron neutron capture therapy(BNCT)on human brain glioma U87 cell line and its mechanisms.Method U87 cells in exponential phase were divided into 6 groups:untreated control,60Co γ 4 Gy,60Co γ 8 Gy,nuclear reactor exposure without boronophenylalanine (BPA)3.5 Gy,BNCT 4 Gy and BNCT 8 Gy.The anti-tumor effects were analyzed through cell morphology,the Annexin V/PI assay by flow cytometer(FCM),and methyl thiazolyl tetrazolium(MTT)assay.The expression of P53 protein was studied by immunocytochemistry and the expression of BCL-2 protein and BAX protein were measured by western blot.Results Typical morphological changes were observed after BNCT irradiation.The apoptotic rates were observed 48 h after irradiation with 65.1%and 85.9%for BNCT 4 Gy and 8 Gy.BNCT showed higher apoptotic rates than those of γ-ray control irradiation (P＜0.01).The expression level of P53 protein was negative in U87,while positive expression of P53 protein was observed in BNCT 4 Gy and 8 Gy groups.BNCT promoted BAX protein expression,at the same time it also inhibited BCL-2 expression.Conclusions BNCT can inhibit the growth of U87 significantly in a dose-dependent and time-dependent patterns. Key words: Boron neutron capture therapy; Glioma; Apoptosis

Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer

BackgroundRecent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated.MethodsThe immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously.ResultsThe Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS.ConclusionThe Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.

Expression of P33ING1, P53 and their relationship with apoptosis in anal canal carcinoma

To explore the expressions of P33ING1, P53 and their relationships with apoptosis in anal canal carcinoma (ACC). The expressions of P33ING1, P53 proteins were measured by immunohistochemistry method (SP method), and apoptosis was detected in 42 cases with ACC, 36 cases with anal canal adenoma (ACA) or anal canal papilloma (ACP), and 40 cases with paraanal inflammatory mass(PAIM). The positive expression rates of P33ING1 and P53 proteins were 40.5% (17/42), 97.2% (35/36) and 97.5% (39/40), 50.0% (21/42), 22.2% (8/36) and 27.5% (11/40) respectively, and the average apoptosis indexes(AI) were (10.27+/- 1.23) per thousand, (42.75+/- 0.98) per thousand and (42.67+/- 1.04) per thousand respectively in ACC, ACA or ACP and PAIM. There were significant differences in the positive expression rates of P33ING1, P53 and apoptosis index between ACC and the other two groups respectively (P< 0.05). Among 21 cases of ACC with positive expression of P53 protein,there were 18 cases with P33ING1 negative expression. P33ING1 expression decrease in ACC, which may play an important role in the carcinogenesis and progression of ACC. P33ING1 and P53 may have an synergistic effect of suppressing cell growth and accelerating cell apoptosis.

Clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer

To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, and the relationships between the p53 and mdm2 protein expression and clinicopathological parameters in pancreatic cancer. The positive expression of p53 protein was found in 40 of 59 patients (67.8%) and that of mdm2 protein in 17 of 59 patients (28.8%). No obvious relationships were found between p53 as well as mdm2 expression and sex, tumor site, TNM staging and histological differentiation. p53 expression was increased in patients younger than 65 years old, while mdm2 had no relationship with age. The survival time of the patients with the positive expression of p53 and mdm2 proteins was obviously shorter than the other groups. Both p53 and mdm2 presented relatively high expression in human pancreatic cancer. The overexpression of p53 and mdm2 might reflect the malignant proliferation of pancreatic cancer and their co-expression might be helpful to evaluate the prognosis of the patients with pancreatic cancer.

Prognostic implication of p53 protein expression in relation to nuclear pleomorphism and the MIB-1 counts in breast cancer

A close correlation of the p53 protein expression to nuclear pleomorphism and proliferative activity in breast cancer has been reported. The prognostic implications of p53 protein expression, however, in relation to nuclear pleomorphism and proliferative activity in breast cancer remain controversial. Nuclear pleomorphism and immunohistochemical reactivity for p53 protein and MIB-1 were evaluated on formalin-fixed paraffin-stored sections from 250 patients with breast cancer for whom the median follow-up duration was 6.4 years. p53 protein expression was positive in 66 (26.4%) of 250 cases. Nuclear pleomorphism was grade I or II in 169 (67.6%) cases and grade III in 81(32.4%)cases. The MIB-1 counts were more than 10% in 102 (40.8%) cases and less than 10% in 148 (59.2%) cases. There was a close correlation between p53 protein expression and nuclear pleomorphism (p<0.0001) and between p53 protein expression and MIB-1 counts (p<0.0001). Univariate analyses showed the 66 cases with positive p53 protein expression to have a significantly (p=0.0284) worse disease free survival (DFS) than the 184 cases with negative p53 protein expression. A multivariate analysis, however, on the variables including all of p53 protein expression, nuclear pleomorphism and MIB-1 counts indicated the MIB-1 counts (p=0.0041) as well as the lymph node status to be independently significant factors for DFS, while neither p53 protein expression nor nuclear pleomorphism were independently significant factors for DFS. The present study demonstrated that the p53 protein expression, nuclear pleomorphism and MIB-1 counts all demonstrated prognostic significance for breast cancer, while the most significant prognostic indicator among these three biological parameters was the MIB-1 counts.

Oral non-Hodgkin lymphomas: studies of EBV and p53 expression.

The aims of the study were to assess sociodemographic and clinicopathologic characteristics of patients with oral non-Hodgkin lymphomas (NHLs) and the expression of Epstein-Barr virus (EBV) and p53. The clinical and pathologic features of 11 patients with oral NHLs were studied. The expression of EBV mRNA and p53 protein were studied by means of in situ hybridization and immunohistochemical methods in 11 formalin-fixed, paraffin-embedded specimens from these patients. The patients' age ranged from 13 to 70 years with the mean of 42 years. Human immuno-deficiency virus (HIV) status was documented in five of the 11 patients and three were known to be HIV-positive. The most common locations were gingiva and alveolar mucosa. Pain and tenderness were major symptoms of the patients. The most common histologic subtype was diffuse large-cell, intermediate-grade NHL. Eight of 11 cases (72.7%) showed positive expression of p53 protein. Four of 10 cases (40%) expressed EBV-encoded RNA (EBER) transcripts. All known HIV-positive cases were EBV-positive. The findings suggest that appropriately expressed p53 protein may play a role in tumorigenesis of oral NHLs. In addition, EBV may be involved with the pathogenesis of oral NHLs particularly in patients with HIV infection.

Correlation between Histological Grade, MIB-1, p53, and Recurrence in 69 Completely Resected Primary Intracranial Meningiomas with a 6 Year Mean Follow-up

Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1 and p53 protein expression. According to the 1993 WHO criteria, revised by Perry et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas, grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The patients were followed until death or for an average of 6.7 years. The 69 meningiomas were divided into two groups, according to the absence (n = 42) or presence (n = 27) of recurrences. In the last group we included 3 patients who died of meningioma recurrence. According to the percentage of MIB-1 positively stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%) and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation between histological grade and MIB-1 LI was statistically significant (p = 0.0006). The correlation between MIB-1 LI and follow-up was also highly significant (p < 0.001): the majority of meningiomas which did not recur (32/42 equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group MIB-1 LI was significantly higher than in the disease-free patients' group. Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the histological grade. In fact, it was significantly higher in recurrent histologically benign meningiomas, as compared with benign meningiomas without recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45 meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%) meningiomas. Although the p53 LI tended to be higher in atypical and malignant meningiomas, no significant correlation was found between the p53 expression and the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling is a useful technique in the routine diagnostic assessment of meningiomas, and helpful in obtaining more information about prognosis and thereby in planning the most suitable treatment.

A case of anaplastic thyroid carcinoma surviving disease free for over 2 years

A 52-year female presented with an enlarged thyroid mass and lump sensation in the throat. The cytologic examination showed class five and she was admitted to the hospital to undergo operation. Total thyroidectomy was done and the tumoral invasion of the trachea was removed. We performed tracheoplasty using a sternocleidomastoid muscle-clavicle myoosseous flap in a single stage operation. Histologic diagnosis revealed anaplastic thyroid carcinoma After upper mediastinal dissection had been performed, systemic chemotherapy using pirarubicin, cisplatin and etoposide was administered. In addition, she was treated with radiochemotherapy using pirarubicin, cisplatin and a total of 58 Gy was administered. No recurrence of the tumor has been noted since the above operation 2 years ago. Immunohistochemical studies of primary and metastatic tissues in this case revealed a positive expression of p53 protein in both.

P53 Overexpression as an Indicator of Overall Survival and Response to Treatment in Osteosarcomas.

The p53 gene located at chromosome 17p13 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twenty-one patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-responders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.