scholarly journals Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 751 ◽  
Author(s):  
Manuel António Campos ◽  
Sofia Macedo ◽  
Margarida Sá Fernandes ◽  
Ana Pestana ◽  
Joana Pardal ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Genetic Profiling ◽  
Ras Mutations ◽  
Logistic Regression Models ◽  
Pattern Of Invasion

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification.

p53 Protein Overexpression in Oral Squamous Cell Carcinomas

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P42-P42
Author(s):  
Sohail M. Awan ◽  
Adnan Syed ◽  
Shehzad Ghaffar
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
P53 Protein ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Protein Overexpression ◽  
P53 Overexpression ◽  
Free Survival ◽  
Disease Free

Objective 1. To determine whether p53 protein expression is prognostic indicator of patient survival. 2. Learn its correlation with habits and histological variables of the tumor in Pakistani patients. Methods A retrospective case series of 140 patients with primary oral squamous cell carcinoma at a tertiary care setting during the period of January 1991 to Dec 2004. p53 protein overexpression was investigated by means of immunohistochemistry. Results of p53 overexpression were evaluated in relation to different clinicopathological parameters and survival. Overall survival and disease-free survival were measured. Event time distributions for these end points were estimated by use of the method of Kaplan and Meier and compared by use of the log-rank statistic. Factors associated with p53 status were selected on cross-tabulations and logistic regression. Cross-tabulations were analyzed by use of the chi-square test or Fisher's exact test, where appropriate. Results were summarized as odds ratio (OR) with corresponding 95% Confidence Interval. Results Overexpression of p53 protein was observed in 75 patients (54%). Patients with p53 negative tumors had improved overall survival (OS) when compared with patients with p53 positive tumors (p=0.036). The p53 overexpression did not correlate with disease-free survival (DFS) (p=0.126), histological differentiation (p=0.611) and patients’ habits (p=0.894) In univariate analysis, AJCC stage, nodal status, tumor size and histological grade were significantly associated with shortened OS and DFS. Conclusions Our study supports that patients with p53 overexpression had a significantly poor overall survival compared to p53 negative patients. However, p53 overexpression was not associated with patients disease-free survival.

scholarly journals Prognostic significance of p16, p53, Bcl-2, and Bax in oral and oropharyngeal squamous cell carcinoma

2014 ◽  
Vol 8 (2) ◽  
pp. 255-261
Author(s):  
Paramee Thongsuksai ◽  
Kowit Pruegsanusak ◽  
Pleumjit Boonyaphiphat
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
P53 Expression

Abstract Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting. Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC. Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins. Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival. Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.

Telomerase catalytic subunit gene expression does not influence survival of patients with squamous cell carcinoma of the larynx and hypopharynx: a case-control study

2005 ◽  
Vol 119 (11) ◽  
pp. 917-921 ◽  
Author(s):  
Boštjan Luzar ◽  
Mario Poljak ◽  
Janez Fischinger ◽  
Ulrika Klopčič ◽  
Nina Gale
Keyword(s):  
Lymph Node ◽  
Squamous Cell ◽  
Lymph Node Metastases ◽  
Regional Lymph Node ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Catalytic Subunit ◽  
Clinicopathological Parameters ◽  
Htert Mrna ◽  
Node Metastases

Aims: to determine correlations between relative quantities of telomerase catalytic subunit m-ribonucleic acid (hTERT mRNA) and conventional clinicopathological parameters (such as site, size and grade of tumour, the presence of regional lymph node metastases, and, in particular, survival) in patients with laryngeal and hypopharyngeal squamous cell carcinomas (SCCs).Material and methods: The relative quantity of hTERT mRNA was analysed by a commercially available LightCycler Telo TAGGG hTERT Quantification Kit in 56 cases of SCC (40 laryngeal and 16 hypopharyngeal). The association with cancer-specific survival was evaluated by univariate and multivariate analysis.Results: Location of the tumour in the hypopharynx was the only significant negative predictive factor for survival, as determined by univariate analysis (p = 0.028). Although a tendency towards a better overall survival was observed for female patients younger than 50 years, for lower tumour grades and sizes, and for the absence of regional lymph node metastases, the prognostic significance of these factors could not be confirmed. No differences existed in hTERT mRNA expression between laryngeal and hypopharyngeal SCCs. Furthermore, no correlation was found between the relative quantities of hTERT mRNA and the tumour size, regional lymph node metastases or survival of patients with laryngeal or hypopharyngeal SCCs.Conclusions: The results of the present study suggest that genetic abnormalities other than telomerase reactivation are responsible for progression of laryngeal and hypopharyngeal SCCs.

scholarly journals High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1132
Author(s):  
Łukasz Jan Adamski ◽  
Anna Starzyńska ◽  
Paulina Adamska ◽  
Michał Kunc ◽  
Monika Sakowicz-Burkiewicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Oral Cavity ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Lower Percentage ◽  
Interleukin 33 ◽  
Impact On Survival

The markers of the tumor microenvironment (TME) are promising prognostic and predictive factors in oral squamous cell carcinoma (OSCC). The current study aims to analyze the immunohistochemical expression of programmed cell death-ligand 1 (PD-L1) and interleukin-33 (IL-33) in a cohort of 95 chemonaïve OSCCs. PD-L1 and IL-33 were assessed separately in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). High PD-L1 expression in TILs was associated with better overall survival (OS) in univariate analysis. Tumors localized in the floor of the oral cavity and tongue tended to have a lower percentage of PD-L1-positive TCs when compared to other locations. PD-L1 expression on TCs had no prognostic significance when the whole cohort was analyzed. However, along with the T descriptor (TNM 8th), it was included in the multivariable model predicting death in carcinomas of the floor of the oral cavity and tongue (HR = 2.51, 95% CI = 1.97–5.28). In other locations, only nodal status was identified as an independent prognostic factor in multivariate analysis (HR = 0.24, 95% CI = 0.08–0.70). Expression of IL-33 had no impact on survival, but it was differently expressed in various locations. In conclusion, the prognostic significance of PD-L1 in oral cancer depends on the tumor site and type of cell expressing immune checkpoint receptor (TCs vs. TILs).

scholarly journals Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Hexin Lin ◽  
Xin Zhao ◽  
Lu Xia ◽  
Jiabian Lian ◽  
Jun You
Keyword(s):  
Malignant Tumors ◽  
Human Cancer ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cancer Prognosis ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Malignant Neoplasms ◽  
Tumor Type

Background. Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods. PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results. Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients’ increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis: HR = 1.81 , 95% CI 1.46-2.25; multivariate analysis: HR = 1.95 , 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma ( HR = 3.31 , 95% CI 2.03-5.39), lung cancer ( HR = 1.66 , 95% CI 1.21-2.29), genitourinary cancer ( HR = 2.03 , 95% CI 1.15-3.58), and digestive cancer ( HR = 1.48 , 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis ( OR = 2.96 , 95% CI 1.42-6.20) and lager tumor size ( OR = 1.60 , 95% CI 1.12-2.28). Conclusion. The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.

Lack of Expression of Galectin-3 Is Associated With a Poor Outcome in Node-Negative Patients With Laryngeal Squamous-Cell Carcinoma

2002 ◽  
Vol 20 (18) ◽  
pp. 3850-3856 ◽  
Author(s):  
Mauro Piantelli ◽  
Stefano Iacobelli ◽  
Giovanni Almadori ◽  
Manuela Iezzi ◽  
Nicola Tinari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Node Negative ◽  
Increased Risk ◽  
Galectin 3

PURPOSE: Galectin-3 is a pleiotropic carbohydrate-binding protein participating in a variety of normal and pathologic processes, including cancer progression. This study was aimed at evaluating the prognostic value of galectin-3 expression in node-negative laryngeal squamous-cell carcinoma (SCC). PATIENTS AND METHODS: Galectin-3 expression was analyzed by immunohistochemistry using M3/38 monoclonal antibody, in a single-institution series of 73 node-negative laryngeal SCC patients (median follow-up, 52 months; range, 2 to 90 months). RESULTS: Forty-two (57.5%) of 73 patients expressed galectin-3. Galectin-3 expression was positively associated with tumor keratinization and histologic grade. A significant correlation was found between galectin-3 tumor positivity and longer relapse-free and overall survival. In univariate analysis, high-grade (grade 3 or 4) tumors, nonkeratinizing tumors, and galectin-3–negative tumors showed a significantly increased risk of relapse and death. In multivariate analysis, only galectin-3 expression retained an independent prognostic significance for both relapse-free and overall survival. CONCLUSION: We conclude that the absence of galectin-3 expression is an independent negative prognostic marker in laryngeal SCC patients. Thus, histochemical detection of galectin-3 in these tumors could be useful for the selection of node-negative patients with potentially unfavorable outcomes, to establish adjuvant therapy protocols.

Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value

1997 ◽  
Vol 86 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Julie M. Cunningham ◽  
David W. Kimmel ◽  
Bernd W. Scheithauer ◽  
Judith R. O'Fallon ◽  
Paul J. Novotny
Keyword(s):  
Univariate Analysis ◽  
Tumor Grade ◽  
Nuclear Antigen ◽  
Clinicopathological Parameters ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Proliferation Markers ◽  
P53 Expression ◽  
Content Type ◽  
Mib 1

✓ Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.

scholarly journals The presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different subsets serve as prognostic factors in advanced hypopharyngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Jie Wang ◽  
Shu Tian ◽  
Ji Sun ◽  
Jiahao Zhang ◽  
Lan Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Free Survival ◽  
Hypopharyngeal Squamous Cell Carcinoma ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Abstract Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.

scholarly journals Expression Profile of Survivin and p16 in Laryngeal Squamous Cell Carcinoma: Contribution of Tunisian Patients

2019 ◽  
Vol 100 (1) ◽  
pp. NP7-NP15 ◽  
Author(s):  
Mariem Ben Elhadj ◽  
Olfa E. L. Amine ◽  
Nehla Mokni Baizig ◽  
Wided Ben Ayoub ◽  
Aida Goucha ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Significance ◽  
Survivin Expression ◽  
Clinicopathological Parameters ◽  
Therapeutic Protocol ◽  
Tunisian Patients ◽  
P16 Expression

The objective of this study was to evaluate the expression of survivin and p16 in laryngeal squamous cell carcinoma (LSCC) in order to analyze their pathogenesis and prognostic significance in Tunisian patients. A total of 70 patients with LSCC collected at the Salah Azaiez Cancer Institute of Tunis were retrospectively evaluated. Expression of survivin and p16 was examined using immunohistochemistry, and the correlations with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS) were statistically evaluated. The positive expression of survivin and p16 were found in 58.6% and 51.43% of LSCC cases, respectively. The p16 expression was not associated with either clinical parameters or patient survival, whereas there was a strong correlation of survivin expression and lymph node metastases ( P = .002), alcohol consumption ( P = .024), and therapeutic protocol (with or without chemotherapy; P = .001). Kaplan-Meier survival curves showed that patients with LSCC having positive survivin expression have shorter OS ( P = .026) and shorter DFS ( P = .01) than those with negative expression. Positive survivin expression was also correlated with high recurrence rate ( P = .014). Therefore, survivin is a poor prognostic marker for LSCC but the therapeutic protocol remains, in multivariate study, the most decisive for the OS and DFS of our patients with P < .01. Our data indicated that, in Tunisian laryngeal squamous cell carcinoma, survivin expression is associated with unfavorable outcomes and represents a predictor marker of recurrence and chemoresistance. However, p16 expression has no prognosis value.

Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (2) ◽  
pp. 668-668 ◽  
Author(s):  
Stephen L. Graziano ◽  
Gary P. Gamble ◽  
Nancy B. Newman ◽  
Lynn Z. Abbott ◽  
Michelle Rooney ◽  
...  
Keyword(s):  
Median Survival ◽  
Squamous Cell ◽  
Early Stage ◽  
Prognostic Significance ◽  
Stage I ◽  
Stage Ii ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
Significant Difference ◽  
Resected Stage

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

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