p63 Expression in 127 Patients with Laryngeal Cancer (original) (raw)
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Laboratory investigation; a journal of technical methods and pathology, 2002
p63 is a p53-related gene that encodes for multiple mRNA transcripts with (TA-p63) or without (DeltaN-p63) transactivating properties on p53-responsive genes. We evaluated for the first time the prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (LSCCs). Moreover, we also assessed the relationships between p63 expression and p53 gene status. p63 IR was detectable in the basal cell layers of non-neoplastic epithelium and in the whole thickness of dysplastic epithelium. All the 150 LSCCs analyzed were immunoreactive for p63, with 28 (18.7%) cases showing p63 IR in </=50% of neoplastic cells. DeltaN-p63 mRNA transcripts were detected in all the 23 tumors analyzed, whereas TA-p63 mRNA transcripts were absent in 5 (21.7%) cases. p53 gene mutations were found in 24 (29.2%) of the 82 cases analyzed and p53 IR was found in 58 (53.7%) of the 108 cases analyzed; neither was associated with p63 IR. No significant assoc...
p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma
Human Pathology, 2005
p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors ( P b .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration ( P b .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression ( P b .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers. D
Advances in Oto-Rhino-Laryngology, 2004
The human p63 gene discovered in 1997 encodes a series of protein isoforms that differ in their N-and/or C-terminal sequences. These isoforms have widely differing properties in promoting or repressing p53-related functions such as growth arrest and apoptosis. In addition, p63 appears to play important roles in the maintenance and differentiation of epithelial cell populations. Many studies have shown that p63, particularly ΔNp63α, is expressed in normal epithelium and also highly expressed in squamous cell carcinomas of surface epithelia. Methods. We have refined the analysis of the expression patterns of p63 isoforms by the use of a quantitative RT-PCR technique applied to micro-dissected normal oral mucosal samples. We have also studied p63 expression in squamous cell carcinoma of the head and neck (SCCHN) compared to normal oral mucosa taken from the same patient. Furthermore, tobacco-exposed buccal mucosa was compared to age and gender matched non exposed controls. RT-PCR for telomerase and immunohistochemical analysis for detection of p53 and Ki-67 proteins was further performed. We also explored the function of p63 in SCCHN cells by using small interfering RNA (siRNA) to silence the expression of different p63 isoforms in cell lines originating from SCCHN. The effect of p63 knockdown was studied using a Fluorescein Diacetate based cytotoxicity assay and immunohistochemistry looking at expression of differentiation markers. The response of the siRNA treated cells to radiation and cytostatic drug was also investigated. We have further studied normal oral wound healing using immunohistochemistry and quantitative PCR. By the use of a macro array comparing siRNA treated cells with non-treated cells a possible connection between the BRCA1 gene and p63 expression was shown and further studied with the use of cHIP and luciferase reporter assays. Results. The p63 isoforms are expressed in normal epithelium, with the highest levels consistently found in basal and parabasal layers. Extensive use of tobacco had no effect on p63. The quantitative PCR showed statistically increased levels of the ΔNp63 and p63β isoforms. No correlation was found between p63-isoform expression patterns and proliferation. The exploration of the function of p63 in SCCHN cells by the use of small interfering RNA (siRNA) showed a statistically significant decreased survival for tumour cells when all p63 isoforms, the N-terminal truncated or the α isoforms were inhibited. No effect on cell proliferation or expression of epithelial differentiation markers was observed. We also demonstrated that inhibition of p63 expression sensitizes cells to the effects of ionizing radiation and cisplatin. The study of normal oral wound healing using immunohistochemistry and quantitative PCR showed significant changes in p63 isoform expression. The ΔNp63 isoform was mainly expressed in the basal layer in the non proliferating and migrating cells while TAp63 was almost absent. The BRCA1 study showed p63 to bind to the BRCA1 promoter and activate the expression of BRCA1 protein. Summary. The p63 proteins have different functions and the balance between the isoforms and their localisation within the epithelium seems to be important for normal wound healing as well as cancer cell survival.
p16 Influence on Laryngeal Squamous Cell Carcinoma Relapse and Survival
Otolaryngology–Head and Neck Surgery, 2019
Objective (1) To identify p16 protein in laryngeal squamous cell carcinoma (LSCC) specimens and to correlate it with the presence of human papillomavirus (HPV) found in these specimens from a previous study. (2) To analyze p16 impact on 10-year overall and disease-free survival. Study Design Retrospective case series with oncologic database chart review. Setting Academic tertiary care hospital. Subjects A total of 123 samples of LSCC (taken from the glottis only) from patients treated with primary surgical resection between 1977 and 2005. Methods p16 protein expression was analyzed through immunohistochemistry and compared with the presence of HPV established in our previous studies. Results were compared with histologic, clinicopathologic, and survival parameters, with a 10-year follow-up. Results Of the samples, 39.02% were positive for p16, but only 11.38% were positive for both p16 and HPV. The p16+ cohort showed a significant improvement in disease-free survival ( P = .0022); s...
Comparison of p63 and p73 expression in benign and malignant salivary gland lesions
Head & Neck, 2005
Background. The p63 and p73 genes are members of the p53 family and play an important role in stem cell identity and cellular differentiation and are expressed in basal and myoepithelial cells. In this study, we examined the expression of p63 and p73 in 50 various benign salivary gland lesions and 45 malignant salivary gland tumors. Methods. The 95 salivary gland tumors were selected from the archives of the Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania. Sectioned formalin-fixed paraffin-embedded tissue cut at 3 Am was immunostained with antibodies that recognize all isozymes of p63 and p73 and evaluated with respect to percentage of positive cells and localization. Results. In benign lesions, p63 and p73 nuclear reactivity was seen in 46 (92%) of 50 and 47 (94%) of 50 cases, respectively. In malignant tumors, p63 and p73 were seen in 34 (76%) of 45 and 40 (89%) of 45 cases, respectively. A significant difference between p63 and p73 positivity was only seen in adenoid cystic carcinomas (p = .006). Also, p73 was found in tumors with minimal basal/myoepithelial differentiation. Conclusions. Hence, p63 and p73 expression is retained in both benign and malignant salivary gland tumors with basaloid or myoepithelial differentiation. Hence, p63 seems to be a more specific marker of myoepithelial differentiation than p73.
Expression of p63 as predictive and prognostic factor in advanced non-small-cell lung cancer
Vojnosanitetski pregled, 2016
Background/Aim. Serbia belongs to the group of countries with a high lung cancer incidence and mortality rate. p63 gene plays an important role in development of lung cancer and immunohistochemical expression of p63 is considered to be a reliable marker for squamous histology. The results of some in vitro studies show a significant association of p63 expression and cisplatin chemoresistance. The aim of this study was to estimate the significance of p63 expression as predictive and prognostic factor in advanced non-small-cell lung cancer (NSCLC). Methods. Expression of p63 in 85 NSCLC (stages III, and IV) was investigated by the use of immunohistochemistry. Four weeks after the completion of 2 cycles of platinum-based doublet chemotherapy all the patients were evaluated based on the treatment response. Kaplan-Meier analysis with log-rank tests were used for overall survival (OS) and progression free survival (PFS) calcultations. Results. The expression of p63 was present in 49.4% of ...
Significance of p63 Amplification and Overexpression in Lung Cancer Development and Prognosis1
2003
The fight against lung cancer is greatly compromised by the lack of effective early detection strategies. Genomic abnormalities and specifically the amplification of chromosomal region 3q26-3qter in lung cancer represent a major signature of neoplastic transformation. Here, we address the significance of p53 homologue p63 mapping to 3q27 in lung tumorigenesis. We analyzed p63 gene copy number (CN) by fluorescence in situ hybridization and expression by immunohistochemistry in tissue microarrays of 217 non-small cell lung cancers (NSCLCs) and correlated them with survival. We additionally characterized our findings in a subset of 24 NSCLCs by reverse transcription-PCR and Western blotting. We analyzed p63 CN and protein expression in 41 preinvasive squamous lesions. The p63 genomic sequence was amplified in 88% of squamous carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was ⌬Np63␣. Western analyses revealed ⌬Np63␣ expression in normal bronchus and squamous carcinomas but not in normal lung or in adenocarcinomas. Furthermore, p63 genomic amplification and protein staining intensity associated with better survival. We found a significant increase in CN in preinvasive lesions graded severe dysplasia or higher. Our data demonstrate that there is early and frequent genomic amplification of p63 in the development of squamous carcinoma of the lung and that patients with NSCLC showing amplification and overexpression of p63 have prolonged survival. These observations suggest that p63 genomic amplification has an early role in lung tumorigenesis and deserves additional evaluation as a biomarker for lung cancer progression.