P53 Immunoexpression Research Articles

Correlations of Hormone Receptors (ER and PR), Her2/neu and p53 Expression in Breast Ductal Carcinoma Among Yemeni Women

Aims: The purpose of this study was to determine if any relationship exists between Estrogen Receptor (ER),Progesterone Receptor (PR), Her2/neu, P53, and clinicopathological factors in female breast ductal carcinoma. Materials and Methods: One hundred and thirty seven (IDC=124, NIDC=13) ductal carcinomas were clinicopathologically and immunohistochemically analyzed and compared with 20 control cases of benign breast lesions in which assessment of Her-2/neu, ER, PR, and P53 has been performed, prospectively. Chi-square analysis was then used to correlate the above observations. Results: The overall immunoexpression of ER, PR, Her2/neu and P53 were 43.8%, 27%, 30.6% and 48.9%, respectively, of the 137 ductal carcinomas. A significant Positive association between ER or PR expression with lymph node involvement was found ( p= 0.004, p= 0.022 respectively), while p53 was found to be negatively associated with lymph nodes involvement (p= 0.03, 0.02, respectively). P53 also associated negatively to lymph node status (P=0.03) and positively with borderline tumor grade (p= 0.03). Conclusion: There are high rates of positive expression of ER, PR, Her2/neu and P53 among Yamani women with breast ductal carcinoma.

Expression of apoptosis regulatory proteins p53, bcl‐2 and bax in recurrent aphthous ulceration

Recurrent aphthous ulceration (RAU) is considered to be an acute inflammatory disease of unknown pathogenesis. Apoptosis may represent an important event in the control of inflammation. The aim of this study was to investigate apoptosis process in RAU using immunohistochemistry. We studied the expression and location of p53, bcl-2 and bax in ulcerated lesions clinically diagnosed as RAU (n = 12) and compared it with that of oral clinically normal mucosa (n = 6) and of other inflammatory chronic disease such as oral fibrous inflammatory hyperplasia (FIH; n = 18). Significant statistically differences (n < 0.05) in p53 expression were noticed in RAU when compared with normal mucosa. No significant statistically differences (P > 0.05) were noticed between FIH and RAU. Bcl-2 and bax did not show remarkable differences between groups. Taken together, the data suggest that RAU induces p53 immunoexpression. Therefore, the protein might be related to the aetiopathogenesis of the ulcerated oral lesions.

Immunoexpression of p53 and hMSH2 in oral squamous cell carcinoma and oral dysplastic lesions in Yemen: Relationship to oral risk habits and prognostic factors

Although several studies analyzed p53 and mismatch repair (MMR) gene expression separately in oral squamous cell carcinoma (SCC), no reports of combined assessment of both proteins in this cancer. The aim of this study was to investigate the roles of p53 and hMSH2 proteins in oral SCC as well as in oral dysplastic lesions (DL) in Yemen. Immunohistochemistry was used to examine the pattern of expression of p53 and hmsh2 proteins in 70 oral SCC and 21 oral DL obtained from Yemeni patients. p53 Immunoexpression was detected in 24 of the 70 oral SCC (34.3%) and 3 of 21 DL (14.3%) with no significant difference between the two groups. On the other hand, reduced expression of hMSH2 was detected in 26 of the 70 oral SCC (37.1%) and 2 of 21 oral DL (9.5%) with a statistically significant difference (P=0.03). Both proteins were significantly related to the grade of tumor differentiation (P=0.007 and 0.02, respectively). There was an inverse correlation between the levels of p53 and hMSH2 immunoexpression in the oral SCC (r=0.42, P=0.01). This study suggested that p53 may play a role in the early stages of oral carcinogenesis, while hMSH2 may be altered in the late stages. More importantly, the roles of p53 and hMSH2 in oral carcinogenesis seem to be interrelated in the pathogenetic pathway of oral SCC. Such a relationship has not been published previously in this type of cancer and needs to be clarified in future studies.

Tubal metaplasia of the endometrium with cytologic atypia: analysis of p53, Ki-67, TERT, and long-term follow-up

Tubal metaplasia of the endometrium may occasionally display cytologic atypia (atypical tubal metaplasia) resembling serous carcinoma or endometrial intraepithelial carcinoma. Although atypical tubal metaplasia is presumed to be reactive or degenerative in etiology, its clinical significance is unknown. In this study, we investigated atypical tubal metaplasia in regard to its immunoexpression of p53, Ki-67, and human telomerase reverse transcriptase (TERT), and its long-term clinical outcome. A total of 63 cases of atypical tubal metaplasia and 200 cases of endometrial samples with typical tubal metaplasia were followed for a mean of 64 and 61 months, respectively. Of the 63 atypical tubal metaplasia cases, formalin-fixed, paraffin-embedded tissue sections from 16 cases were immunostained with antibodies to p53, Ki-67, and TERT. Sections from 13 cases of uterine serous carcinoma were also stained for TERT as control. After long-term follow-up, 5% of patients in the atypical tubal metaplasia group developed hyperplasia without atypia compared with 4% of patients in the control group (P=0.44), whereas 3% in the atypical tubal metaplasia group developed atypical hyperplasia or carcinoma compared with 2% in the control group (P=0.44). p53 immunoreactivity was either focal and weak or negative in all cases of both atypical and typical tubal metaplasia (P>0.05). Ki-67 immunoreactivity was present in 0–5% of cells in 94% of both atypical and typical tubal metaplasia (P>0.05). TERT immunoexpression was absent in all 16 cases of atypical tubal metaplasia, but present in all 13 cases of uterine serous carcinoma (P<0.0001). Our study indicates that atypical tubal metaplasia displays an immunostaining pattern similar to otherwise typical tubal metaplasia of the endometrium, and distinct from uterine serous neoplasms. The presence of atypical tubal metaplasia in endometrial samplings does not increase the risk of developing endometrial hyperplasia or malignancy.

Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis

Immunohistochemical staining for p53 is used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites including ovarian cancers. Strong and diffuse immunoexpression of p53 is generally interpreted as likely indicating a TP53 gene mutation. The immunoprofile that correlates with wild-type TP53, however, is not as clear. In particular, the significance of completely negative immunostaining is controversial. The aim of this study was to clarify the relationship of the immunohistochemical expression of p53 with the mutational status of the TP53 gene in ovarian cancer. A total of 57 ovarian carcinomas (43 high-grade serous ovarian/peritoneal carcinomas, 2 malignant mesodermal mixed tumors (carcinosarcomas), 2 low-grade serous carcinomas, 4 clear cell carcinomas, 1 well-differentiated endometrioid carcinoma, and 5 carcinomas with mixed epithelial differentiation) were analyzed for TP53 mutations by nucleotide sequencing (exons 4–9), and subjected to immunohistochemical analysis of p53 expression. Thirty six tumors contained functional mutations and 13 had wild type TP53. Five tumors were found to harbor known TP53 polymorphism and changes in the intron region were detected in three. Tumors with wild-type TP53 displayed a wide range of immunolabeling patterns, with the most common pattern showing ≤10% of positive cells in 6 cases (46%). Mutant TP53 was associated with 60–100% positive cells in 23 cases (64% of cases). This pattern of staining was also seen in three cases with wild-type TP53. Tumors that were completely negative (0% cells staining) had a mutation of TP53 in 65% of cases and wild-type TP53 in 11%. Combining two immunohistochemical labeling patterns associated with TP53 mutations (0% and 60–100% positive cells), correctly identified a mutation in 94% of cases (P<0.001). Immunohistochemical analysis can be used as a robust method for inferring the presence of a TP53 mutation in ovarian carcinomas. In addition to a strong and diffuse pattern of p53 expression (in greater than 60% of cells), complete absence of p53 immunoexpression is commonly associated with a TP53 mutation. Accordingly, this latter pattern, unlike low-level expression (10–50% cells), should not be construed as indicative of wild-type TP53.

Avaliação da superexpressão da proteína p53 e das mutações no éxon 8 do gene TP53 em carcinomas mamários caninos e glândulas normais

Este estudo foi realizado com o objetivo de avaliar a expressão da proteína p53, pela técnica de imuno-histoquímica, em neoplasmas mamários malignos em cadelas, além de investigar mutações no éxon 8 do gene supressor Tp53 por meio do padrão de bandas obtidas por PCR-RFLP. Dezenove mamas de cadelas saudáveis foram usadas como controle (Grupo 1). Amostras de 18 casos de tumores malignos (Grupo 2) e suas glândulas mamárias contralaterais (Grupo 3) foram obtidas na rotina do Hospital Veterinário da UFRPE. Os tumores foram identificados histologicamente e classificados em graus de malignidade. O método da estreptoavidina-biotina peroxidase foi utilizado para a análise da expressão de p53 por imuno-histoquímica, de acordo com a localização e intensidade da coloração. A expressão da proteína p53 não foi observada nas amostras do Grupo 1, mas foi encontrada em todas as amostras de tumores malignos (Grupo 2) seja só no núcleo, ou também no citoplasma. No Grupo 3, a expressão foi observada em quatro amostras normais e em duas que apresentavam tumor. Para a análise molecular, o DNA genômico foi extraído e submetido à PCR-RFLP com as seguintes endonucleases: AluI, BsoBI, DdeI e SmaI. O padrão de bandas foi polimórfico entre os grupos, mas não entre as variantes tumorais. Esse polimorfismo detectou mutações no fragmento estudado - éxon 8 do gene Tp53 - que podem resultar em alterações nos nucleotídeos, localizados nos sítios de restrição das enzimas. Esses achados levam a conclusão de que a imunoexpressão da p53 não tem relação com o subtipo histológico ou grau de malignidade do tumor, mas sim com a presença dos tumores no tecido mamário de cadelas. A PCR-RFLP pode ser usada como importante ferramenta para o estudo da carcinogênese mamária na cadela, possibilitando gerar diagnósticos precoces através do polimorfismo obtido com endonucleases de restrição pré-selecionadas.

P16 protein status and response to treatment in a prospective clinical trial (ECOG 2303) of patients with head and neck squamous cell carcinoma (HNSCC).

e16032 Background: p16 immunoexpression is considered a surrogate biomarker for the presence of functional Human Papillomavirus oncoprotein E7 in HNSCC. We sought to determine the association betwe...

Effect of human papillomavirus on cell cycle-related proteins p16INK4A, p21waf1/cip1, p53 and cyclin D1 in sinonasal inverted papilloma and laryngeal carcinoma. An &lt;i&gt;in situ&lt;/i&gt; hybridization study

Human papillomavirus (HPV) infection is implicated as an important risk factor in the development of head and neck cancers. Many studies focusing on the relationships between HPV infection and cell cycle proteins immunoexpression in laryngeal lesions have provided contradictory results. The aim of this study was to evaluate the relationships between HPV DNA presence and p16INK4a, p21waf1/cip1, p53 and cyclin D1 immunoexpression in heterogenous HPV-positive and HPV-negative groups of laryngeal cancers and inverted papillomas. The HPV DNA expression was detected using an in situ hybridization method and immunoexpression of p16INK4a, p21waf1/cip1, p53 and cyclin D1 using immunohistochemistry. The immunoexpression of p21waf1/ /cip1 and p53 proteins was lower in the HPV-positive group compared to the HPV-negative group, although only the difference of p53 staining was statistically significant. The immunoexpression of p16INK4a and cyclin D1 was significantly increased in the HPV-positive group compared to the HPV-negative group. The increased immunoexpression of p16INK4a and cyclin D1, and the lower immunoexpression of p21waf1/cip1 and p53 in the HPV-positive group compared to the HPV-negative group, supports the hypothesis that HPV may play an important role in cell cycle dysregulation.

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16(INK4a) in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16(INK4a) expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16(INK4a) expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16(INK4a) and hTERT.

Oral leukoplakias with different degrees of dysplasia: comparative study of hMLH1, p53, and AgNOR

hMLH1 is one of the major proteins of the mammalian mismatch repair system. It has been suggested that the mismatch repair machinery could be linked to p53, a tumor suppressor protein. The AgNOR technique is used to assess cell proliferation. The aim was to compare the immunoexpression of hMLH1 and p53, and AgNOR number in oral leukoplakias with different degrees of dysplasia. Sixty-two samples were evaluated by immunohistochemistry for hMLH1 and p53, and AgNOR technique, being 17 without dysplasia, 19 with mild dysplasia, 16 with moderate dysplasia, and 10 with severe dysplasia. hMLH1 immunoexpression showed decreasing indexes, while p53 and AgNOR showed increasing indexes from lesions with lower degrees of dysplasia to lesions with more severe dysplasia. An inverse correlation between hMLH1 and both p53 and AgNOR, and a direct correlation between p53 and AgNOR were observed. Alterations in the immunoexpression pattern of hMLH1 and p53 seemed to be early events in oral carcinogenesis. During acquisition of a more dysplastic phenotype, keratinocytes may show diminished capacity of DNA repair and tumor suppression, as well as higher cellular proliferation, and these pathways can be somehow interconnected.

Immunohistochemical detection of p53 and PCNA in ameloblastoma and adenomatoid odontogenic tumor

Although ameloblastoma and adenomatoid odontogenic tumor (AOT) belong to the same group according to the World Health Organization, they show different biologic behaviors. PCNA, an amplifier of cell proliferation, and p53, a tumor suppressor protein, are overexpressed in some odontogenic lesions. The purpose of this study was to immunohistochemically evaluate the expression of p53 and PCNA to clarify the possible role of these proteins in different behaviors of ameloblastoma and AOT. The immunohistochemical expression of PCNA and p53 was determined in 30 solid ameloblastomas and 12 AOTs. Statistical tests including one-way ANOVA, t-test, chi-square, Mann-Whitney U and Kendall were used to analyze the data. All tissue sections (except one specimen of plexiform ameloblastoma) exhibited immunoexpression for p53. PCNA was expressed in all specimens. There was no significant difference in PCNA expression between ameloblastomas and AOTs (P > 0.05). For p53, there was no statistical difference between subtypes of ameloblastomas (P > 0.05), whereas statistical differences were observed between ameloblastomas and AOTs (P < 0.001). There was no statistical difference in PCNA intensity of staining between ameloblastomas and AOTs (P > 0.05), whereas the p53 intensity in ameloblastomas was stronger than AOTs (P < 0.05). Positive correlation between PCNA and p53 was observed. We concluded that PCNA overexpression is not responsible for the difference in clinical behavior of these two lesions, whereas the expression of p53 in ameloblastoma may explain the more aggressive nature of this tumor compared with AOT.

Prognostic and predictive values of E-cadherin for patients of ovarian clear cell adenocarcinoma.

The purpose of the study was to analyze negative versus positive immunoexpression of epithelial cadherin (E-cadherin) and p53 in patients with primary advanced ovarian clear cell adenocarcinoma (OCCA) and its significance in relation to clinical features, progression-free survival and overall survival (OS). Protein expression of E-cadherin and p53 was immunohistochemically evaluated in 61 OCCA patients with stages IIC to IV. The clinical factors studied included stage, age, CA-125, residual tumors, and chemotherapy regimens. Positive p53 immunoexpression was 44.8% (26/58) of OCCAs; in contrast, E-cadherin immunoexpression was observed in 75.9% (44/58) of OCCAs. The expected 5-year OS rate of OCCA treated with paclitaxel-based chemotherapy was significantly better than non-paclitaxel-based chemotherapy (40% vs 0%, P = 0.001). The expected 5-year OS rate of OCCA patients with positive E-cadherin immunoexpression (>10%) was also significantly better than patients with negative E-cadherin immunoexpression (≤10%) (35% vs 0%, P = 0.02). The expected 5-year OS rate of those receiving paclitaxel-platinum chemotherapy was not significantly different from platinum-based chemotherapy for those with negative E-cadherin immunoexpression (P = 0.11). The expected 5-year OS rate of those receiving paclitaxel-based chemotherapy was better than non-paclitaxel-based chemotherapy for those with positive E-cadherin immunoexpression (43% vs 0%, P = 0.01). Paclitaxel-based chemotherapy and positive E-cadherin immunoexpression were 2 independent prognostic factors in OS of patients with OCCA (P = 0.01 and 0.04, respectively). E-cadherin is a useful prognostic marker for OCCA patients, and paclitaxel-based chemotherapy can improve survival among patients with positive E-cadherin immunoreactivity.

Significance of topoisomerase IIIβ expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase IIIβ, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase IIIβ in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase IIIβ, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase IIIβ was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase IIIβ correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase IIIβ expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase IIIβ expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.

Clinical Significance of Heme Oxygenase-1 Expression in Non-Muscle-Invasive Bladder Cancer

Introduction: In several malignant diseases, elevated heme oxygenase-1 (HO-1) is associated with progression or resistance to chemotherapy. We evaluated the clinical significance of HO-1 expression in non-muscle-invasive bladder cancer. Patients and Methods: We examined 109 patients with non-muscle-invasive bladder cancer. The immunoexpression of HO-1, p53, and Ki-67 was analyzed using paraffin-embedded tissue from transurethral resection in comparison with the clinicopathological variables. Results: Positive expression of HO-1 was found in 66 of 109 tumors (61%), and the positivity of HO-1 correlated significantly with high tumor grade and the altered expression patterns of p53 and Ki-67. In our analysis of 16 cases treated by intravesical administration of anthracyclines, the positive expression of HO-1 correlated with poor disease-free survival (p = 0.015). In in vitro experiments using urothelial cancer cell lines, HO-1 upregulation was observed by exposure to doxorubicin. Moreover, siRNA-mediated suppression of HO-1 upregulation sensitized the urothelial cancer cells to doxorubicin. Conclusions: Our findings suggested that resistance against anthracyclines correlated with HO-1 and expression analysis of HO-1 may be a useful predictive marker for intravesical administration of anthracyclines.

Multicentric reticulohistiocytosis and urologic carcinomas: a possible paraneoplastic association

Multicentric reticulohistiocytosis (MR) is a rare non-Langerhans histiocytosis that is characterized by cutaneous nodules and severe destructive arthritis. Although 25-30% of reported cases have been associated with internal malignancies, the pathophysiology of MR is unknown. Herein, we report two cases of MR that were associated with urologic neoplasms. Because the tumor suppressor gene p53 may play a role in the biology of other histiocytoses, we investigated its p53 immunoexpression in these two cases. Both cases were positive immunohistochemically, but it remains to be seen whether this finding is truly important in the pathogenesis of MR associated with underlying visceral neoplasms.

Canine Gastric Carcinoma

Immunohistochemical staining for cell cycle proteins and heat shock proteins was performed on 17 canine gastric carcinomas. The immunoexpression of p53, p21, p16, Hsp27, and Hsp70 was investigated. A study was conducted to determine the histological type and parameters related to tumor malignancy. Possible associations and trends were assessed between the immunoexpression of each protein and tumor type as well as specific parameters of malignancy. High intratumor frequency of cellular p53 immunostaining was observed (61.96% average), but lower frequencies of p21 and p16 expression were present (34.65% and 10.41%, respectively). The p53 overexpression was associated with tumor infiltration (P = .0258). Expression of p21 was lower in undifferentiated carcinomas, and the loss of expression was associated with histopathological parameters characteristic of a poor prognosis such as lymphatic vessel invasion (P = .0258). The lack of p16 immunoreactivity was related to histopathological characteristics of malignancy such as the presence of evident and multiple nucleoli (P = .0475). In contrast, deep tumor infiltration was observed in those carcinomas with a high p16 index (P = .0475). Hsp70 appeared to be overexpressed in all gastric neoplasms included in this study. This is in contrast to Hsp27, because a group of tumors showed complete lack of Hsp27 immunoexpression, whereas the others displayed extensive Hsp27 immunostaining. The differences in Hsp27 did not correlate with any of the histopathological parameters, but Hsp27 immunoexpression was higher in the undifferentiated carcinoma. No significant differences in the expression of the proteins were found in canine gastric carcinomas according to their histological type. These findings may be useful for establishing a prognosis for canine gastric carcinoma.

Erratum to: P53 immunoexpression as a prognostic marker for human astrocytomas: a meta-analysis and review of the literature

Erratum to: P53 immunoexpression as a prognostic marker for human astrocytomas: a meta-analysis and review of the literature

Analysis of the immunohistochemical expressions of p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and their correlations with the prognostic factors

Search of tumors markers that allow treatment with higher survival rates, and indicate the response to treatment and recurrence of cancer To analyze the immunoexpression of the proteins p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and correlate them with the clinical-pathological prognostic factors. Tissue microarray paraffin blocks were made from colorectal adenocarcinoma tissue resected from 82 patients who had undergone surgery but not chemotherapy or radiotherapy, at "Hospital São Paulo", São Paulo, SP, Brazil, between 2002 and 2005. Thin sections (4 microm) were subjected to immunohistochemical reactions, and immunoexpression staining scores were obtained. The scores were correlated with the degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The study variables were analyzed using the chi-square and Kaplan-Meier tests to investigate associations with the markers. The significance of the differences between the curves of the disease-free interval and survival was analyzed using the Logrank and Wilcoxon tests. The immunohistochemical expression of p53 was positive in 70 tumors (85.4%) and negative in 12 (14.6%). The expression of bcl-2 was positive in 26 (31.7%) and negative in 56 (68.3%). The expression of Ki-67 was positive in 62 (75.6%) and negative in 20 (24.4%). There was no statistically significant correlation between the expressions of these markers separately or in conjunction, in relation to the degree of cell differentiation, staging, disease-free interval, survival and specific mortality. In relation to recurrence, there was a statistically significant correlation with positive expression of Ki-67 (P = 0.035). The immunohistochemical expression of Ki-67 in colorectal cancer is associated with recurrence of this disease.

P53 immunoexpression as a prognostic marker for human astrocytomas: a meta-analysis and review of the literature

During the past few decades, researchers have been looking for parameters with an impact on the prognosis of patients with astrocytic tumors. p53 is one of the most widely investigated molecules in human gliomas. We aimed to comprehensively review the evidence for the prognostic usefulness of p53 immunohistochemical expression in paraffin-embedded tissue specimens from diffusely infiltrating astrocytomas. We conducted a systematic review of the PubMed database through December 2007 to identify cohort studies that evaluated p53 immunohistochemical expression as a prognostic marker for human astrocytomas. Estimates of significance were extracted from association tests and hazard ratios with 95% CI from actuarial curves and Cox regression analyses. A meta-analysis was performed on the studies that applied Cox models and had adjusted the hazard ratio of p53 expression with tumor grade and patients' age. We reviewed 44 publications (including 3,627 patients), 14 of which included the estimates (HR and 95% CI) derived from Cox regression. Descriptive analysis showed that most of the published articles did not contain information on important variables such as sex and age (missing from 25% and 11% of studies, respectively), previous treatment, tissue-retrieval and follow-up period (56%). The quantitative synthesis showed that p53 expression is not a significant prognostic factor (combined HR = 1.034, P = 0.531). There was no significant between-study heterogeneity and publication bias. A second meta-analysis performed only on glioblastomas showed that the overall risk of mortality in these tumors was -0.123 (-0.346 to 0.100) and was not statistically significant. After almost 20 years of research, published evidence does not substantiate the usefulness of p53 immunohistochemical expression as a prognostic marker in patients with astrocytic neoplasms.

The clinicopathologic values of the molecules associated with the main pathogenesis of the glioblastoma

Glioblastoma (GBM) is a malignant CNS neoplasm. The prognosis of GBM may be influenced by the molecules of p53/MDM2/p14ARF, RB/p16INK4a, and the EGFR/PTEN/protein kinase B (PKB)/phosphoinositide 3-kinase (PI3K) pathways. We studied the expression status of specific molecular markers in GBMs by immunohistochemistry (IHC) and FISH in correlation with the clinical outcomes. The positivity of EGFR FISH and those of EGFR IHC by pharmDx and Zymed antibodies were 64.9%, 73.5%, and 43.4%, respectively. EGFR pharmDx antibody was more sensitive but less specific than EGFR Zymed antibody. p53 overexpression, MDM2 expression, p16 loss, PTEN loss, PKB and PI3K expression were found in 48.2%, 26.5%, 56.6%, 21.4%, 15.7% and 6.0%, respectively. EGFR IHC and FISH significantly, although not completely, correlated and EGFR and p53 immunoexpression also showed positive correlation. On multivariate survival studies, old age (≥ 40 yrs) and bilaterality were independent unfavorable prognosis factors ( p < 0.05). Stratified by age, resectability and tumor size < 5 cm were favorable survival factors in young (40 < yrs) and old age groups (≥ 40 yrs), respectively. Furthermore, the patients with supratentorial tumor lived longer than the patients with infratentorial tumor ( p < 0.05). Longer survival (survival length, ≥ 3 years) was statistically less frequent in the patients in the EGFR FISH-positive group ( p = 0.031).