P53 Expression In Patients Research Articles

Zinc chloride may regulate hematopoietic stem cell aging and pro-inflammatory cytokines in systemic lupus erythematosus

Background: The immune cells of patients with systemic lupus erythematosus (SLE) age earlier than those of normal subjects. However, the senescence of circulating hematopoietic stem cells (HSCs) in patients with SLE is not well understood, and it is unclear whether zinc treatment can regulate the senescence and proinflammatory cytokine production of HSCs in these patients. Methods: Clinical data were collected on 38 patients with SLE and 35 healthy controls (HCs), and the complete blood count, circulating HSC number, and p16 (a senescence marker) expression in the peripheral blood of these participants were analyzed via flow cytometry. Pooled circulating HSCs were isolated using leukapheresis. The effects of zinc chloride exposure on the pooled HSCs of each group were determined in vitro. Levels of the proinflammatory cytokines IL-6 and IL17, regulatory cytokine TGF-β, p16, and regulator T-cells (Tregs) were evaluated 72 h after incubation with 50 or 100 µM zinc chloride. Results: The number of circulating HSCs did not differ between the two groups (p=0.1685). The expression of p16 in HSCs was higher in the SLE group than in the HC group (p = 0.0043), and patients with SLE exhibited higher levels of IL-6, IL-17, and p16 in pooled HSCs (p =0.0025, p<0.0001, and p = 0.0003, respectively), although TGF-β levels did not differ between the groups (p=0.9816). Zinc chloride reduced IL-6, TGF-β, IL-17, and p16 expression in patients with SLE toward HC levels. Treg frequency in pooled HSCs was comparable between the groups (p=0.3997), although a 100 µM zinc chloride treatment significantly depleted the Treg population of patients with SLE (p=0.0001). Conclusions: Circulating HSCs in SLE are more aged and produce more proinflammatory cytokines. Zinc chloride treatment might prevent immunoaging and inhibit proinflammatory cytokine–producing cells in patients with SLE.

Implication of cytoplasmic p53 expression in pulmonary neuroendocrine carcinoma using next-generation sequencinganalysis.

Cytoplasmic p53 expression indicates a high frequency of TP53 abnormalities in gynaecological carcinoma. However, the implication of this expression in pulmonary neuroendocrine carcinoma (NEC) remains unclear. Thus, our study aimed to fill this research gap. Immunohistochemistry (IHC) of p53 was performed on 146 cases of resected small-cell lung carcinoma and large-cell NEC, and next-generation sequencing was conducted on cases showing cytoplasmic and wild-type p53 expression. IHC revealed overexpression in 57% of the cases (n = 83), complete absence in 31% (n = 45), cytoplasmic expression in 8% (n = 12) and wild-type expression in 4% (n = 6) of the cases. TP53 mutations were identified in nine of the 13 cases with available genetic analysis. The TP53 mutation rates in cases with cytoplasmic and wild-type p53 expression were 88% (seven of eight) and 40% (two of five), respectively. All seven cases showing cytoplasmic expression with TP53 mutations harboured loss-of-function type mutations: four had mutations in the DNA-binding domain, two in the nuclear localisation domain and one in the tetramerisation domain. Clinically, cases with cytoplasmic p53 expression had a poor prognosis similar to that in cases with p53 overexpression or complete absence. Cytoplasmic p53 expression in patients with pulmonary NEC suggests a high TP53 mutation rate, which is associated with a poor prognosis similar to that in patients with p53 overexpression or complete absence. This cytoplasmic expression should not be misidentified as a wild-type expression. This is the first report, to our knowledge, that demonstrates the implication of cytoplasmic p53 expression in pulmonary NEC.

Positive p16 Immunostaining Is an Independent Prognostic Variable for Disease-free Survival and Overall Survival in Patients With Squamous Cell Carcinoma of the Vulva Treated With Radical Surgery and Inguinofemoral Lymphadenectomy: An Italian Single Center Retrospective Study.

The expression of the cyclin-dependent kinase inhibitor p16 correlates with the presence of human papillomavirus. The purpose of this investigation was to assess the prognostic relevance of p16 expression in patients with vulvar squamous cell carcinoma (VSCC) treated with radical surgery followed by adjuvant (chemo) radiation in selected cases. Seventy-eight patients were analyzed retrospectively. Positive p16 immunostaining was detected in 19 (24.4%) patients. Five-year disease-free survival (DFS) and 5-year overall survival (OS) were better in p16-positive compared to p16-negative patients (83.9% versus 37.3% p=0.002 and 91.7% versus 57.6%, p=0.003, respectively). p16 expression retained prognostic relevance at multivariate analysis for both DFS and OS. p16 expression was detected in 24.4% of patients with VSCC and was found to be an independent prognostic variable for both DFS and OS.

EXPRESSION OF P53 PROTEIN ASSOCIATES WITH ANTI-PD-L1 TREATMENT RESPONSE ON HUMAN-DERIVED XENOGRAFT MODEL OF GATA3/CR5/6-NEGATIVE RECURRENT NONMUSCULAR INVASIVE BLADDER UROTHELIAL CARCINOMA

Annotation: The study investigated the prognostic role of p53 expression in patients with GATA3 / CR5 / 6-negative recurrent nonmuscular invasive bladder cancer on the background of anti-PD-L1 treatment using a xenograft model in immunodeficient BALB / c nu / nu mice obtained from a patient. Twenty lines of patient-derived xenografts of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The expression of p53 protein is an independent factor affecting the animals’ survival time of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative nonmuscular invasive bladder cancer. P53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression

ObjectiveHigh-grade cervical lesions (HSIL) are associated with the presence of high-risk HPV types, tissue expression of p16, and increased chance of malignant progression, requiring surgical intervention. To improve risk evaluation, we assessed the discriminatory power of the histological findings associated with p16 immunohistochemistry (IHC) staining to classify the low-grade cervical lesion (LSIL) and HSIL. MethodsWe collected cervical biopsies from colposcopy-visible lesions and non-affected tissue (adjacent to the lesions) of 62 Brazilian women and labeled them with anti-p16 antibodies. In addition to the observational pattern and labeling to define the latent classes (affected vs. non-affected), a computational tool was used for semi-quantitative analysis of p16 expression. The intensity of staining of the nucleus or cytoplasm was captured using the Gimp 2.10 software. ROC curves were used to determine cutoff values for p16 expression in patients classified as LSIL and HSIL by latent class statistics for each labeling stratum. Resultsp16 nuclear labeling showed the best sensitivity and specificity to discriminate LSIL with low p16 expression (62%) and HSIL with high p16 expression (37%). Many patients whose lesions had intermediate levels of p16 nuclear staining were subsequently stratified according to the expression of p16 in the cytoplasm, indicating that five of 21 LSIL were at risk of progression, and 13 of 41 HSIL at risk of regression. ConclusionsWe suggest a hierarchical analysis, with histology at the first level, followed by a labeling analysis in the nucleus and then in the cytoplasm to increase the accuracy of the HPV cervical lesion stratification.

Reprint: Peculiarities of expression of apoptosis markers in the tissues of primary fallopian tubes carcinoma

Aim: immunohistochemical analysis of apoptosis markers in the tissue of PFTC. Introduction: Primary fallopian tubes carcinoma is a rare case among oncological diseases of female genital organs, but the mortality rate is rather high. Nowadays, the prognostic factors of this neoplasia are not fully determined. The data on the p53 and bcl2 proteins expression and their use as prognostic factors in patients with malignant tumors of many locations are contradictory. Methods: the study was conducted on 66 samples of fallopian tubes tumor tissue. To study the apoptosis peculiarities of tumor cells the mouse monoclonal antibodies for bcl-2 (clone 100/D5) and p53 (clone SP5) were used. Mathematic calculations were done using Microsoft Excel 2010 with AtteStat 12.0.5. Results: The high expression of p53 was found in patients of all clinical stages. Mutations of p53 increased with spreading of the neoplastic process. Strong correlation of p53 presence in tumor samples and clinical stage of the disease was determined (r=0.77). In contrast to the abovementioned protein the study of bcl-2 showed the moderate negative correlation between this protein and the stage of the disease (r=−0.54). Analysis of the dependence of p53 expression with the presence or absence of lymph nodes metastasis showed a direct correlation between the indicators (r=0.25). Thus the level of p53 expression in patients with N1 was 80.6±2.7% compared with the N0 group (29.7±3.6%). The stage of neoplasia differentiation is in moderate direct correlation with p53 expression (r=0.58) and in inverse with – bcl-2 (r=−0.64). Conclusion: Expression of p53 depends on neoplasia spreading and stage of tumor differentiation. The expression of p53 is an independent prognostic marker for N-status and helps to classify the patients into “risk” groups.

The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment.

BackgroundPreclinical and clinical data indicate that p53 expression might modulate the activity of the epidermal growth factor receptor (EGFR), influencing response/resistance to anti-EGFR monoclonal antibodies. However, the association between p53 status and clinical outcome has not been clarified yet.ObjectiveIn our study, we evaluated the role of p53 expression in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort.Patients and Methodsp53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Survival distribution was assessed by the Kaplan–Meier method, while the log-rank test was used for survival comparison.ResultsAmong 120 patients with RAS/BRAF wild-type mCRC included in our analysis, 52 (59%) and 19 (59%) patients showed p53 overexpression in the exploratory and validation cohort, respectively. In the exploratory cohort, low p53 expression was correlated with better median progression-free survival (hazard ratio 0.39; p < 0.0001), median overall survival (hazard ratio: 0.23; p < 0.0001) and response rate (p < 0.0001). These results were confirmed by data of the validation cohort where we observed better median progression-free survival (hazard ratio: 0.48; p = 0.0399), median overall survival (hazard ratio: 0.26; p = 0.0027) and response rate (p =0.0007) in patients with p53 normal expression mCRC.ConclusionsIn our study, p53 overexpression was associated with anti-EGFR treatment resistance in patients with RAS/BRAF WT mCRC, as confirmed in a validation cohort. Larger studies are needed to validate the role of p53 and investigate EGFR cross-talk in these patients.

Discrepancy in p16 expression in patients with HPV-associated head and neck squamous cell carcinoma in Thailand: clinical characteristics and survival outcomes

BackgroundLower prevalence HPV infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. We therefore evaluated the characteristic and association of p16 and HPV in Thai patients with HNSCC.MethodsWe used immunohistochemistry and qPCR, respectively, to detect p16 and HPV DNA in archrival formalin-fixed paraffin-embedded HNSCC tissues. Patient characteristics and survival were analyzed.Resultsp16 expression was detected in tumors of 72 of 662 (10.9%) patients with HNSCC and was significantly associated with higher-grade histology, advanced nodal stage, and oropharynx. p16 was expressed in 28 and 6.5% of patients with OPSCC or non-OPSCC, respectively, and HPV DNA was detected in 15.6 and 1% of patients, respectively. Using p16 as a surrogate for HPV status, sensitivities were 80 and 25% in OPSCC and non-OPSCC, respectively. Positive and negative predictive rates of OPSCC were 38 and 95%. Discordance rates between HPV and p16 were 23 and 7% in OPSCC and non-OPSCC, respectively. Overall survival (OS) were significantly longer in both p16-positive OPSCC (p = 0.049), and non-OPSCC (p = 0.003).ConclusionsLow prevalence of p16 and HPV associated OPSCC and non-OPSCC were confirmed in Thai patients. High discordance and low positive predictive rates of p16 were observed in HPV-associated OPSCC. p16 was a significant prognostic factor for OS for patients with OPSCC or non-OPSCC. Therefore, HPV testing should be performed to assess the association of HPV with HNSCC regardless of p16 expression.

Correlation of p53 expression with Clinical Presentation and Prognosis of Oral Squamous Cell Carcinoma Patients: A Pilot Study.

Mutations of p53 gene is one of the most common events in human cancers including oral squamous cell carcinoma (OSCC). However, its role in carcinogenesis and association with regard to prognosis is still under investigation and unclear. The aim was to study the expression of p53 in patients of OSCC and correlation with clinical presentation and prognosis. In this retrospective observational pilot study, we examined expression of p53 in 50 histologically diagnosed cases of OSCC and correlated it with initial clinical presentation and clinical events in follow up period. p53 expression was significantly negative (94%) in patients with history of only oral tobacco consumption while cases with additional history of smoking or alcohol were positive (p = 0.0001 and 0.011). On the other hand, aggressive course of the disease was found to be significant with p53 positivity in the form of lymph nodal extension (13 out of 17 cases) (p = 0.011) and recurrence (6 out of 10 cases) (p = 0.024). p53 was overexpressed (positive) in predisposing factors like smoking and alcohol but not in OSCC associated with chewing tobacco. p53 overexpression is also associated with advanced TNM stage. To the best of our knowledge, this is the first report where association of p53 overexpression and oral tobacco consumption associated OSCC was not observed and we recommend that carcinogenic events in chewing tobacco induced OSCC should be studied separately for its unique set of mutations.

Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.

PurposeOur previous studies suggested that p53-positive triple-negative breast cancer (TNBC) should be more sensitive to chemotherapy than p53-negative TNBC. The aim of this study was to determine whether p53 expression in TNBC could predict response to neoadjuvant chemotherapy and the resulting prognosis.MethodsFrom January 2009 to December 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated.ResultsTwo patients (22.2%, 2 of 9) achieved pCR in p53(+) TNBC and 4 patients (50%, 5 of 10) achieved pCR in p53(−) TNBC. There was no correlation between pCR rate and p53 expression (P = 0.350). Based on prechemotherapy p53 expression, there was no significant difference in disease-free survival (DFS) between p53(+) TNBC and p53(−) TNBC (P = 0.335). However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(−) TBNC (P = 0.099). Based on prechemotherapy p53 expression, p53(+) TNBC had better overall survival (OS) than p53(−) TNBC, but the difference was not statistically significant (P = 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(−) TNBC (P = 0.018).ConclusionImmunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53(+) TNBC had a better OS than p53(−) TNBC in patients who underwent neoadjuvant chemotherapy.

Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.

119 Background: Triple negative breast cancer (TNBC) exhibits a higher rate of early recurrence and more aggressive behavior. Despite unfavorable prognoses, TNBCs are known to be highly reactive to chemotherapy and show higher pathologic complete response rates after neoadjuvant chemotherapy. However, TNBC patients with residual cancer have significantly worse prognoses than patients with non-TNBC associated residual cancer. TP53 mutations are the most common genetic alterations in breast cancer and are highly linked to basal subtype carcinomas. Past studies have investigated if TP53 mutation can predict the response of cancer to chemotherapy or affect a difference in prognosis; however, the lack of consistent results has hampered clinical applications. Because immunostaining studies can be easily performed, those results may be more useful until Next generation sequencing results are clinically applicable. The aim of this study was to determine whether p53 expression in TNBC could predict the response to neoadjuvant chemotherapy and the resulting prognosis. Methods: From 2009 to 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. Results: Two patients (22.2%, 2/9) achieved pCR in p53(+) TNBC and four patients (50%, 5/10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression ( P= 0.350). Based on pre-chemotherapy p53 expression, there was no significant difference in DFS between p53(+) TNBC and p53(-) TNBC ( P= 0.335) . However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC ( P= 0.099). Based on pre-chemotherapy p53 expression, p53(+) TNBC had better OS than p53(-) TNBC, but the difference was not statistically significant ( P= 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC ( P = 0.018). Conclusions: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53 (+) TNBC had a better OS than p53 (-) TNBC in patients who underwent neoadjuvant chemotherapy.

Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer, characterized by the highest mortality rate among other RCC subtypes due to the occurrence of metastasis and drug resistance following surgery. The Von Hippel-Lindau tumor suppressor (VHL)-hypoxia-inducible factor 1 subunit α (HIF1A)/hypoxia-inducible factor 2α (HIF2A)-vascular endothelial growth factor A (VEGFA) protein axis is involved in the development and progression of ccRCC, whereas sunitinib, a tyrosine kinase inhibitor, blocks the binding of VEGFA to its receptor. The aim of the present study was to examine the possible association of the gene expression of VHL, HIF1A, HIF2A, VEGFA and tumor protein P53 (P53) in cancer tissue with the outcome of ccRCC patients who were treated with sunitinib as first-line therapy following nephrec-tomy. A total of 36 ccRCC patients were enrolled, 11 of whom were administered sunitinib post-operatively. Tumor and control samples were collected, and mRNA and protein levels were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. High mRNA and protein expression levels of HIF2A and VEGFA were found to be associated with shorter overall survival (OS) and progression-free survival (PFS) rates, as well as with unfavorable risk factors of cancer recurrence and mortality. Resistance to sunitinib was also observed; the OS and PFS rates were shorter (median OS and PFS: 12 and 6 months, respectively, vs. undetermined). Sunitinib resistance was associated with high HIF2A and VEGFA protein levels (b=0.57 and b=0.69 for OS and PFS, respectively; P<0.001). Taken together, the findings of this study suggest that the protein levels of HIF2A and VEGFA in tumor tissue may serve as independent prognostic factors in ccRCC. ccRCC patients with increased intratumoral HIF2A and VEGFA protein levels, and unaltered VHL protein levels, are not likely to benefit from sunitinib treatment following nephrectomy; however, this hypothesis requires verification by large-scale replication studies.

Correlations of ultrasonic features with severity of liver cancer and p16 expression in patients with liver cancer.

This paper analyzes the correlations of ultrasonic features with clinical-pathological manifestations and p16 expression in patients with liver cancer. A total of 84 patients with primary liver cancer were randomly enrolled. The characteristics of liver cancer were examined via conventional ultrasound and contrast-enhanced ultrasound (CEUS) before operation. The p16 protein expressions in liver cancer and para-carcinoma tissues were detected via immunohistochemistry (IHC), and the correlations of p16 positive expression with ultrasound parameters were also analyzed. It was manifested via ultrasound that 6.4% (3/47) of stage I-II liver cancer showed the equal-echo change in portal phase, while others faded and showed the equal-echo change with 32.4% (12/37) of stage III-IV liver cancer. There were no statistically significant differences in ultrasonic features of patients in stage I-II and stage III-IV in the arterial and delayed phases (p>0.05). The positive expression rate of p16 protein in para-carcinoma tissues was 85.71% (72/84) which was significantly higher than that in liver cancer tissues (30.95%, 26/84) (p<0.05). Maximum intensity (IMAX), time to peak (TTP) and mean transit time (mTT) had no statistically significant differences between the p16 positive and negative groups, but there were statistically significant differences in rising slope (RS) and washout time (WT) (p<0.05). Correlation analyses revealed that the positive expression of p16 had no significant correlations with IMAX, mTT and TTP (p>0.05), but it positively correlated with RS (correlation coefficient r=0.377, p<0.05) and negatively correlated with WT (r=-0.410, p<0.05). Conventional ultrasound and CEUS can evaluate the expression of p16 protein in liver cancer repeatedly and non-invasively. The evaluations therefore have great significance in clinical treatment of liver cancer.

Prognostic Significance of Human Papilloma Virus and p16 Expression in Patients with Vulvar Squamous Cell Carcinoma who Received Radiotherapy

AimsHuman papilloma virus (HPV) has been identified as an aetiological agent in a subset of patients with vulvar squamous cell carcinoma (VSCC). The prognostic role of HPV status in VSCC patients treated with radiotherapy has not yet been determined. We investigated the associations between HPV, p16 and clinical outcome in these women. Materials and methodsPatients undergoing potentially curative radiation treatment for VSCC at a single institution from 2000 to 2009 were retrospectively identified. Those who received definitive or peri-operative radiotherapy as part of treatment, and who had available pathological specimens, were included for analysis. HPV infection was detected using Roche Linear array hybridisation and p16 by immunohistochemistry. The locoregional relapse (LRR) rate was estimated using a cumulative incidence function to account for competing risks. Disease-free survival (DFS) and overall survival were analysed using the Kaplan–Meier method. The median follow-up was 4.9 years. ResultsForty patients were suitable for analysis, with a median age of 69.5 years. HPV was detected in 14/40 (35%) patients, HPV16 being the most common serotype (79%). Patients with HPV-positive tumours had lower 5 year LRR compared with those with HPV-negative tumours (14.3% versus 79.3%, Gray test P = 0.003). Tumour p16 positivity was also associated with lower 5 year LRR (15.4% versus 81.2%, Gray test P = 0.002). Patients with p16-positive tumours had higher 5 year DFS compared with those with p16-negative tumours (62% versus 7%, Log-rank test P = 0.02). ConclusionsWe have identified a favourable prognostic group in VSCC, with p16-positive patients showing improved outcomes. p16 has the potential to be a predictive marker allowing the identification of women more likely to have a favourable response to radiotherapy.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery.

Prognostic impact of p16 expression in patients with oropharyngeal squamous cell carcinoma (OSCC) undergoing surgery is not fully examined. The aim of this study was to clarify these issues. Sixty-four OSCC subjects were analyzed. Immuno-histochemical staining of p16, a surrogate marker for human papillomavirus (HPV), was performed histopathologically. Data were retrospectively analyzed according to p16 positivity and factors linked to prognosis were also analyzed. No significant difference was observed in the prognosis between the p16-positive group (n=28) and the p16-negative group (n=36). In patients undergoing post-operative radiation, the p16-positive group (n=18) had a significantly better prognosis than the p16-negative group (n=6). On multivariate analysis, transoral surgery was a significant predictor of overall survival (p=0.0173). Prognostic impact of p16 can be emphasized in a subgroup of OSCC patients undergoing surgery. Surgery with sufficient surgical margin may be chosen as the first treatment for HPV-negative OSCC in some cases.

Prognostic Significance of Immunohistochemical P53 Expression in Patients with Breast Cancer

Prognostic Significance of Immunohistochemical P53 Expression in Patients with Breast Cancer

P53-expression in patients with renal cell carcinoma correlates with a higher probability of disease progression and increased cancer-specific mortality after surgery but does not enhance the predictive accuracy of robust outcome models

ObjectiveDue to lacking external validation, molecular biomarkers are currently not applied for risk-stratification of patients with localized renal cell carcinoma. The objective of this study was to externally validate a molecular multi-marker panel included in a previously proposed prognostic nomogram for the prediction of postoperative disease-free survival. Methods and materialsBesides pathologic tumor stage (pT) and ECOG-Performance Status, the nomogram includes 5 molecular markers (Ki-67, p53, VEGFR-1 endothelial or epithelial, and VEGF-D epithelial). The validation cohort comprised 343 renal cell carcinoma patients treated by radical nephrectomy or nephron-sparing surgery from 1999 to 2004 at a single academic center (median follow-up: 100 months). By multivariable Cox proportional-hazards regression models, the impact of clinical and molecular markers included in the nomogram on disease progression (DP) and cancer-specific mortality (CSM) was assessed; in addition, it was evaluated to what extent molecular markers added to the models’ predictive accuracy (PA). ResultsOf all parameters included in the nomogram, ECOG-PS and pT-stage only revealed a significant impact on both endpoints. p53 (per 10% measures) showed a significant impact on DP (HR = 1.31; P = 0.008), albeit not on CSM, while all other molecular markers did not impact study endpoints. Using Martingale residuals, a cut-off value for p53-expression<20% (negative) vs. ≥20% (positive) yielded the highest impact on DP and CSM. In outcome-models including further well-established histo-pathological factors, p53-expression dichotomized at 20% independently impacted DP (HR = 4.13; P = 0.004) and CSM (HR = 3.74; P = 0.033), while no significant PA gain was achieved. Conclusionsp53 showed a statistically significant impact on DP, albeit not on CSM, when applying the 10% expression cut-off as used in the original nomogram, while the prognostic value of all other examined markers included in the nomogram could not be confirmed. When an alternative cut-off of 20% was applied in multivariable models, p53 independently impacted DP and CSM, while the PA was not significantly enhanced. Hence, the clinical significance of p53 is still to be determined. Based on the results of this study it is not recommendable to use p53-expression and the Klatte nomogram in routine clinical decision-making.

P53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis

BackgroundTumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC.MethodsPublications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study.ResultsFinal 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians.Conclusionsp53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

Abstract IA16: Current and emerging molecular diagnostic assays for colorectal cancer

Abstract IA16: Current and emerging molecular diagnostic assays for colorectal cancer

A cross-sectional study of p53 expression in patients with squamous cell carcinoma cervix: A hospital-based study

Context: Cervical cancer is the second most common cancer in women in India and the fourth most common cancer in women worldwide. The p53 is a tumor suppressor gene. Overexpression of p53 is detected by immunohistochemistry (IHC) and it indicates a worsened prognosis in some malignancies. Aims: The present study was undertaken to assess the expression of p53 by IHC in normal cervical epithelium and squamous cell carcinoma (SCC) cervix. The role of p53 as a potential biomarker by correlating p53 expression with clinico-pathological parameters was also studied. Settings and Design: Cross-sectional study. Subjects and Methods: A total of 50 cases of cervical biopsy or hysterectomy specimens of SCC cervix and fifty cases of hysterectomy specimens for other gynecologic causes were included in the study. IHC was used to study the p53 expression in normal and neoplastic cervical epithelium. The p53 positivity was assessed by using a semi quantitative method in SCC cervix. The p53 expression was correlated with various clinico-pathological parameters. Statistical Analysis Used: Data collected was analyzed using appropriate statistical test. Results: All the fifty cases (100%) of SCC cervix showed positive p53 expression. The normal cervical epithelium in 90% cases was p53 negative and 10% showed basal layer positivity. A statistically significant correlation was seen between p53 score and menopausal status ( P = 0.010). Conclusions: Overexpression of p53 is suggestive of high grade of tumor.