P53 Oncoprotein Expression Research Articles

Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels

BackgroundHepatitis C virus (HCV) was reported to relate to polymorphous and frequent extrahepatic manifestation. Despite the limited studies, HCV viral oncoproteins may be implicated in breast cancer (BC) tumor aggressiveness. In a trial to elucidate a mechanistic link, this study aimed to investigate a mutant p53 and c-Myc oncoprotein expression levels in BC patients with and without HCV infection.MethodsA total of 215 BC patients (119 infected and 96 non-infected with HCV) were collected. ELISA was used for detection of anti-HCV antibodies, mutant p53, c-Myc, HCV-NS4, CEA, CA 125, and CA-15.3.ResultsHCV infection was related to BC late stages, lymph-node invasion, distant metastasis, high grades, and large size. HCV-infected patients had a significantly (P < 0.05) higher WBCs, ALT and AST activity, bilirubin CEA, CA125 and CA15.3 levels, and reduced hemoglobin, albumin, and RBCs count. Regardless of tumor severity, HCV infection was associated with significant elevated levels of mutant p53 (22.5 ± 3.5 µg/mL; 1.9-fold increase) and c-Myc (21.4 ± 1.8 µg/mL; 1.5-fold increase). Among HCV-infected patients, elevated levels of p53 and c-Myc were significantly correlated with elevated tumor markers (CEA, CA 125, and CA15.3) and HCV-NS4 levels.ConclusionsThis study concluded that HCV infection may be accompanied with BC severity behavior and this may be owing to elevated expression of mutant p53 and c-Myc oncoproteins.

P53/MDM2 Complex-Based Targeted Strategies in Colon Adenocarcinoma.

In the current molecular review, we describe the mechanisms of TP53/MDM2 deregulation and their impact on the colon adenocarcinoma molecular substrate and phenotype. Among the genes that are critically altered in carcinogenesis, the TP53 tumor suppressor gene is of major importance. The TP53 gene (gene locus: 17p13.1) regulates the cell cycle by controlling the G1/S and G2/M checkpoints securing the normal sequence of cell cycle phases. Furthermore, it is involved in apoptosis programmed cell death. The gene is mutated or epigenetically altered in all epithelial malignancies, including colon adenocarcinoma. Additionally, Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3), acts as a major negative regulator for p53 expression in the p53-MDM2 auto-regulatory pathway. MDM2 binds directly to p53 and represses its transcriptional activity, promoting p53 degradation. CONCLUSION: In colon adenocarcinoma, MDM2 oncogene overexpression directly influences p53 oncoprotein expression levels.

SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer

Background and aims: In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7].

MON-309 Intratumoral Proliferation and Proinflammatory Macrophages in Obese and Non-Obese Patients with Different Molecular-Biological Types of Endometrial Cancer

Background and aims: Endometrial cancer (EC) is characterized in times of modern obesity epidemic by the rapid incidence increase and the recent update of the molecular-biological classification, which now distinguishes not two, as before, but four types of this tumor (Kandoth et al., 2013; Talhouk et al., 2017; Berstein et al., 2017) that need to be comprehensively studied. The objective of this work was to compare the proliferative potential of a tumor tissue (Ki67 index) and compare it with the expression of proinflammatory CD68-macrophages in obese and non-obese patients with different types of EC according to the PROMISE classification. Materials and methods: In all predominantly postmenopausal 216 treatment naive EC patients included in the study, the body mass index (BMI) was estimated due to which the females were divided into subgroups with BMI ≥30.0 and <30.0. According to genetic (high-resolution melting and sequencing) and immunohistochemical (DACO antibodies) analysis, endometrial carcinomas were classified in accordance with recommendations (Talhouk et al, 2017) into types with POLE gene mutations, defect of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and variant without characteristic molecular profile, WCMP. Immunohistochemistry was also used to evaluate the expression of Ki67 (DBS antibodies, clone SP6) and CD68 (DAKO antibodies, clone CD8/144B). Results: Obesity was more common in patients with a WCMP tumor type and, especially, in MMR-D group (BMI ratio ≥30.0/<30.0, respectively, 1.62 and 2.32). The highest Ki67 index values were detected with positive (59.3 ± 3.8%) and a combination of positive and diffuse (50.5 ± 3.7%) p53 expression, and the lowest (27.6 ± 1.7%) in the WCMP group. In all EC types (except for cases with p53+), Ki67 expression was lower at BMI ≥30.0, which was confirmed within this subgroup by negative Spearman correlation of Ki67 level with BMI value. CD68 expression showed a downward trend in the MMR-D and WCMP types (124.4 ± 7.8 and 115.0 ± 5.9 cond.un.) and a tendency to positive correlation with Ki67 in obese women belonging to the POLE and p53 groups. Conclusions: The findings suggest that the level of such important prognostic tumor markers as Ki67 and CD68 (Soeda et al., 2008) is characterized by a relationship with the presence/absence of obesity as well as with EC molecular-biological type, that expands target range for preventive and therapeutic interventions. Acknowledgement to grant 18-015-00026

Risk Categorization with Different Grades of Cervical Pre-Neoplastic Lesions - High Risk HPV Associations and Expression of p53 and RARβ

Objective:To identify high risk HPV associations by evaluating linked p16 overexpression and also the expression of p53 and RARβ together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials and Methods:Immunohistochemical staining was performed on 100 cases of cervical pre- neoplastic lesions for expression of biomarkers like p16, p53 and RARβ for comparison with haematoxylin/eosin (HE) findings. All the experimentally generated data were statistically analyzed.Results:In this study 70% cases showed overexpression of p16INK4A increasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seen in 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% cases showed negative immunoreactivity for the putative tumor suppressor gene RARβ (p>0.05).Conclusion:Our study provides support for the idea that p16 can be used to identify associations with HPV , as well as having potential along with p53 and RARβ for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion. Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as well as histopathology.

P53 Immunohistochemistry Expression in Wilms Tumor: A Prognostic Tool in the Detection of Tumor Aggressiveness

We studied whether immunohistochemical expression of p53 in Wilms tumors correlates with tumor aggressiveness. We also examined whether preoperative chemotherapy results in any alteration of p53 expression. A total of 18 patients underwent preoperative chemotherapy and 30 underwent immediate surgery for Wilms tumor. All children were younger than 10 years and had histologically confirmed disease. Patients with a bilateral tumor or a syndrome related to Wilms tumor were excluded. All pathology slides were uniformly stained for p53 protein, and p53 staining density and intensity were scored. The p53 scoring was then compared to the clinical behavior of the Wilms tumor, ie unfavorable tumor staging, and survival and recurrence rates. In the direct surgery and the preoperatively treated groups p53 positivity correlated with unfavorable Wilms tumor staging (p = 0.007). In addition, a positive p53 correlation predicted poorer survival (p = 0.017). Interestingly patients who underwent preoperative chemotherapy had an increased intensity of p53 staining compared to the direct surgery group (p <0.001). This study provides preliminary evidence that a higher score for immunohistochemical p53 expression correlates with unfavorable Wilms tumor staging and predicts poorer survival. This test could become a useful addition to the current histopathological analysis of Wilms tumor.

Study of P53 Oncoprotein Expression and S-Phase Fraction to Predict Radiotherapy Response in Patients with Oropharyngeal Carcinoma

Study of P53 Oncoprotein Expression and S-Phase Fraction to Predict Radiotherapy Response in Patients with Oropharyngeal Carcinoma

Immunohistochemical expression of p53 oncoprotein in Wilms tumour in relation to histological components, histological types and preoperative chemotherapy

There have been only few studies of immunoexpression of p53 in Wilms tumour (WT), and their results are somewhat contradictory. The aim of the study was to determine p53 immunohistochemical expression in WT in relation to its histological components, histological prognostic types classified according to the SIOP Working Classification of Renal Tumours of Childhood (2001), and influence of preoperative chemotherapy. The analyses are based on 79 primary WTs treated in single institution according to SIOP protocols between 1983-2001. For the immunohistochemical detection of p53, the monoclonal p53 antibody (DO-7, DAKO) was used. Semiquantitative grading of nuclear staining was done. The immunoexpression of p53 was significantly higher in the blastemal and epithelial than in the stromal component (p < 0.001). It was significantly correlated to WT histological prognostic types (p = 0.039).The exensivity of p53 immunoexpression was higher in anaplastic components but a difference between WT type of diffuse anaplasia and all other types was nonsignificant (p = 0.10). Five blastemal type WTs were p53 immunopositive and four immunonegative. There was no difference in p53 immunopositivity between WT treated with the preoperative chemotherapy and primary resected WT (p = 0.88). The immunoexpression of p53 in WT was significantly higher in the blastemal and epithelial than in the stromal component. It was in significant correlation with histological types of WT. The anaplastic component had noticeable but statistically not significantly higher p53 immunoexpression than non-anaplastic. The preoperative chemotherapy did not modify p53 immunoexpression of WT which had been found in other similar studies.

Human papilloma virus and p53 expression in bladder cancer in Egypt: Relationship to schistosomiasis and clinicopathologic factors

The aim of the current study was to compare the role of p53 and human papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated carcinoma of the urinary bladder. To achieve this aim, we investigated 114 bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for human papillomavirus by in situ hybridization technique. The results revealed that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas. In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein expression was significantly higher in poorly differentiated tumors. However, it was significantly higher in locally more invasive tumors in the schistosomal carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in situ. These results suggest that p53 immunohistochemistry can be a prognostic factor in both schistosomal and nonschistosomal bladder cancer. More importantly, HPV does not seem to play a role in the pathogenesis of either type of bladder cancer in our country.

Flow cytometric analysis of p53 oncoprotein expression in cutaneous melanoma

Mutation of the p53 tumour suppressor gene is thought to represent a significant step in the development of over half of all human cancers. Qualitative investigations of p53 protein in cutaneous melanoma suggest that overexpression is more common than in other tumours. This study analysed p53 protein expression using flow cytometry as a quantitative assay. Expression of p53 protein was assayed in ten benign melanocytic naevi (BMN) and 50 surgically excised ethanol-fixed melanomas. Nuclei were stained for the p53 protein with Pab1801 and analysed using flow cytometry. Protein expression was further correlated with clinicopathological parameters. None of the BMN was immunopositive for p53. Forty-one of the 50 melanomas stained positively. The overall median positivity for p53 in primary melanoma was 12.8 per cent compared with 22.5 per cent in metastatic disease. No association was found between p53 expression and Breslow thickness or presence of nodal and skin metastases. Overexpression of p53 was associated with ulceration, mitotic figures and lymphocytic infiltration, and there was a striking increase of p53 expression with age. Expression of p53 was inversely correlated with disease-free interval. Although overexpression of p53 is common in melanoma, there was no association with major clinical parameters such as Breslow thickness and overall survival. The association found between p53 and other clinicopathological features suggests that the tumour suppressor gene does play a role in the evolution of melanoma.

Immunohistochemical Expression of p53, MDM2, and p21Wafi Oncoproteins in Endometriomas But Not Adenomyosis

p53, MDM2, and p21Waf1 are oncoproteins that regulate the cell cycle. The purpose of this study was to examine the distribution of p53, MDM2, and p21Waf1 oncoprotein expression in endometriomas and in adenomyosis. Tissue samples from 25 women with pathologically confirmed endometriomas and 31 women with pathologically confirmed adenomyosis were analyzed. Expression of p53, MDM2, and p21Waf1 oncoproteins was assessed by immunohistochemical nuclear staining. p53, MDM2, and p21Waf1 expression were detected in 20%, 60%, and 80% of endometrioma tissue samples, respectively. All endometrioma tissue samples expressing p53 also tested positive for both MDM2 and p21Waf1. MDM2 expression was significantly higher in the proliferative than in the secretory phase of the cycle. In contrast, all 31 adenomyosis tissue samples were negative for p53, MDM2, and p21Waf1 expression. The expression of p53, MDM2, and p21Waf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis.

Expression of Hypoxia-Inducible Factor-1α Protein Predicts Survival in Patients with Transitional Cell Carcinoma of the Upper Urinary Tract

Hypoxia-inducible factor-1 (HIF-1), identified as one of the transcription factors, has been found to play an essential role in oxygen homeostasis. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta. Increased levels of HIF-1alpha have been reported during the carcinogenesis and progress of several tumors. We investigated the prognostic importance of HIF-1alpha expression in transitional cell carcinoma of the upper urinary tract. In 127 cases of transitional cell carcinoma of the upper urinary tract, we examined its expression (using immunohistochemistry and in situ hybridization), and also its relation to the expression of p53 oncoprotein, as well as to proliferating cell nuclear antigen (PCNA) immunoreactivity, microvessel density, clinicopathologic parameters, and clinical outcome. A positive expression of HIF-1alpha protein was recognized in 55.1% of samples, the expression being apparent within the nucleus in tumor cells. HIF-1alpha protein expression correlated with grade, growth pattern, p53 oncoprotein expression, and PCNA index, but not with stage. Furthermore, a significant correlation was found between HIF-1alpha protein expression and both overall and disease-free survival rates in the univariate and multivariate analyses (in all tumors and in invasive tumors). A positive expression of HIF-1alpha mRNA was recognized in 69.6% of 125 samples which were available, the expression being apparent within the cytoplasm in tumor cells. The positive expression of HIF-1alpha mRNA by in situ hybridization correlated significantly with HIF-1alpha protein expression by immunohistochemistry. HIF-1alpha mRNA expression only correlated with pattern of growth (P = 0.0078). In conclusion, the detection of HIF-1alpha protein would seem to be of value in informing the prognosis of transitional cell carcinoma of the upper urinary tract.

Cell turnover of serrated adenomas

Serrated adenomas of the colon are characterized by epithelial neoplasia combining the architectural features of hyperplastic polyps and the cytological features of adenomas. Cell turnover, which is related to the malignant potential of these polyps, has not been thoroughly investigated. The aim of this study was to investigate epithelial cell proliferation, apoptosis, and oncoprotein expression in serrated adenomas. Twenty-five hyperplastic polyps, 25 serrated adenomas, and 25 tubulovillous adenomas resected from the colons of 75 patients were studied by immunohistochemical staining using monoclonal antibodies against MIB-1, Bcl-2, Bax, p53, and the TUNEL method for the detection of apoptosis. In serrated adenomas, the proliferation rate was significantly lower than in tubulovillous adenomas in both the lower and the upper parts of the crypts, and higher than that of hyperplastic polyps. Apoptosis was also significantly lower in serrated than in tubulovillous adenomas, but higher than in hyperplastic polyps. p53 oncoprotein expression was significantly greater in both serrated and tubulovillous adenomas than in hyperplastic polyps. bcl-2 protein expression was higher only in tubulovillous adenomas. Bax index was significantly different between tubullovillous and serrated adenomas, but the lowest values were observed in hyperplastic polyps. Serrated adenomas are highly proliferative polyps. They should be considered a biologically different entity from hyperplastic polyps. The intermediate features between serrated adenomas, hyperplastic polyps, and tubulovillous adenomas using the antibodies analysed in this study could have implications for the rate or the mechanism of development of malignancy in this type of polyp.

Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia.

Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. In the absence of intestinal metaplasia, both the apoptotic index (0.0272 +/- 0.011 vs 0.0128 +/- 0.006) and expresssion of p53 (35.55 +/- 31.16 vs 18.33 +/- 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P < 0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 +/- 0.004 vs 0.011 +/- 0.004), or p53 ratio (70.16 +/- 22.54 vs 68.50 +/- 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P < 0.05). In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

Comparative Study of p53 Mutation and Oncoprotein Expression in Gastric Adenocarcinoma

Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than ), twelve cases as postive (more than ). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P

Expression of survivin does not predict survival in patients with transitional cell carcinoma of the upper urinary tract.

The members of the IAP (inhibitors of apoptosis) family, which includes survivin, have recently emerged as modulators of an evolutionarily conserved step in apoptosis. Survivin is present during embryonic and fetal development, but it is downregulated in normal adult tissues. However, it becomes re-expressed in a variety of cancers. We investigated the prognostic importance of the expression of survivin in transitional cell carcinoma of the upper urinary tract (TCC-UUT). In 126 cases of TCC-UUT, we examined its expression (using immunohistochemistry), and also its relationship with the expressions of bcl-2 oncoprotein, p53 oncoprotein, and proliferating cell nuclear antigen (PCNA) immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of survivin was recognized in 12.7% of samples, a granular pattern being apparent within the cytoplasm of tumor cells. Survivin expression did not correlate with clinicopathologic findings, bcl-2 oncoprotein expression, p53 oncoprotein expression, PCNA index, or prognosis. In the normal urothelium, its expression was not detected. In conclusion, the expression of survivin does not predict prognosis in TCC-UUT.

Human immunodeficiency virus infection, Bcl-2, p53 protein, and Ki-67 analysis in ocular surface squamous neoplasia.

To determine the age and human immunodeficiency virus (HIV) status of patients with ocular surface squamous neoplasia (OSSN), and to analyze tumor proliferation, Bcl-2, and p53 oncoprotein expression in OSSN. Only patients with histologically proved neoplasia were included in this study. The HIV status was obtained only with informed consent. Monoclonal antibodies to p53 and Bcl-2 protein were used after microwave antigen retrieval to enhance immunohistochemical staining of the sections. Proliferation was assessed by means of Ki-67 antigen expression. Positive staining in each specimen was expressed as a percentage and graded accordingly. Forty-one eyes in 40 black patients with a mean age of 37 years were found to have OSSN. Of the 41 lesions, 35 represented in situ or invasive carcinoma. The remaining 6 had mild or moderately dysplastic lesions. Seventeen patients agreed to an HIV test and, of these, 12 (70.6%) were HIV positive. All 12 were younger than 50 years, and 11 had either carcinoma in situ or invasive lesions. Twenty-two of 40 lesions expressed significant (greater than 50% of neoplastic cells) p53 positivity, while Bcl-2 expression was detected in 10. Ki-67 expression was low, even in the HIV-positive lesions. At our institution, OSSN occurs in young patients, many of whom are HIV positive. Expression of p53 is a common finding, whereas Bcl-2 immunoexpression occurs in the minority of cases. Ki-67 analysis showed that OSSN is a slow-growing tumor, even in the presence of HIV infection.

Expression of cyclins D1, p21 and p53 oncoprotein: correlation with mammographic appearance in non-palpable and palpable T1N0 breast carcinomas

Expression of cyclins D1, p21 and p53 oncoprotein: correlation with mammographic appearance in non-palpable and palpable T1N0 breast carcinomas

Correlation of p53 oncoprotein expression with chemotherapy response in small cell lung carcinomas

p53 oncoprotein expression was investigated in small cell lung carcinomas (SCLC) using immunohistochemical staining with antibodies against p53. A total of 50 pre-treatment biopsies were examined. We analyzed the relationship between p53 expression and these patients’ relevant clinical characteristics, response to chemotherapy, time to progression, and overall survival. We found p53 overexpression in 46% of the samples but no association with clinical data or overall survival. Our results show a strong correlation of p53 staining with chemotherapy response. Multivariate analysis selected p53 as an independent predictive factor of chemotherapy response.

Expression of p27Kip1 Protein in Transitional Cell Carcinoma of the Upper Urinary Tract

The expression of p27Kip1, a negative regulator of the cell cycle, has been reported to correlate with the biological behavior and prognosis of several tumors. However, its prognostic importance in transitional cell carcinoma of the upper urinary tract (TCC-UUT) has not previously been investigated. We investigated p27Kip1 protein expression using immunohistochemistry in 132 cases of TCC-UUT and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, p53 oncoprotein immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of p27Kip1 protein was recognized in 94.7% of the samples and was apparent within tumor nuclei. In the normal urothelium, its expression was identified in all cell layers. A positive expression of p53 oncoprotein was recognized in 27.2% of the patients. The PCNA index was 7.4 to 93.1% (mean, 66.4%). Examination of the relationships between the expression of p27Kip1 protein and clinicopathologic findings, PCNA index, and the expression of p53 oncoprotein revealed that the expression of p27Kip1 protein decreased significantly with stage and grade. In a univariate analysis of disease-free and overall survival rates, no correlation was found between the expression of p27Kip1 protein and prognosis. The expression of p27Kip1 protein appears to be of little or no value in informing the prognosis in TCC-UUT.