P63 Expression Research Articles

Correlation between immunohistochemical expression of Ki-67and P63 and aggressiveness of urinary bladder urothelial carcinoma

ABSTRACT Urothelial carcinoma is the most common urinary malignancy with a wide proportion of cancer morbidity and mortality. The aim of the present study is to evaluate Ki-67 and p63 immunoexpression and their correlation with grade and stage of bladder urothelial carcinoma. Fifty cases of bladder urothelial carcinoma were investigated and were submitted to immunohistochemical staining for p63 and Ki-67, which were assessed qualitatively and quantitatively. A high percentage of p63 immunoexpression showed a significant association with low-grade tumors (P < .05), while Ki-67 mean percentage of expression was higher in high-grade tumors, advanced stage and multiple tumors compared to low grade, early-stage and single tumors without statistical association. Furthermore, the mean percentage of p63 was higher in urothelial carcinoma with squamous differentiation compared to pure urothelial carcinoma with an absence of statistical significance. P63 could help in the identification of bladder tumors with squamous differentiation since identifying these cases is important regarding prognostic and therapeutic aspects. Ki 67 seems to be associated with features of bladder tumor progression as multiplicity, high grade and advanced stage.

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report

BackgroundPulmonary NUT carcinoma is rare, but lethal, thus, must not be overlooked. The definitive diagnosis is made by a NUT monoclonal antibody or gene analysis, but these are not always routinely available. Therefore, the diagnosis depends on this rare disease being suspected from the clinical and pathological findings. Generally, NUT carcinoma of the lung occurs near the hilum in younger adults with severe subjective symptoms. Histologically, it is characterized by the monomorphic growth of small cells which showed positivity of p63 immunohistochemistry.Case presentationAn 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 and p40 protein expression was not detected.ConclusionsThis is the first case of pulmonary NUT carcinoma to show negativity for p63 and is the oldest among previously reported cases. The present case suggests that NUT carcinoma should be suspected when the morphology of monomorphic growth of small cells without lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression.

Epithelial Distribution of E-Cadherin, p63, and Mitotic Figures in ApoTome Images to Determine the Oncogenic Potentiality of Oral Submucous Fibrosis.

The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.

P63 expression profile in uterine cervical lesions

Background and objective: P63 is a member of the p53 gene family. It plays an essential role in the normal development of the cervix. This study aimed to assess p63 expression in different cervical lesions and the correlation between their expression in cervical intraepithelial neoplastic changes and invasive cervical cancer. Methods: A total of 62 cervical tissues were performed for p63 immunostaining, including 15 samples of non-neoplastic reactive cervicitis, 27 cervical intraepithelial neoplastic changes, and 15 invasive cervical cancer cases as well as five samples of normal cervical tissue as control. Results: P63 in normal cervical squamous epithelium had restricted staining pattern in the nuclei of basal cells. Reactive cervicitis staining ranged from restricted staining pattern in basal cells to mild increase in staining intensity involving upper parabasal cells. P63 was positive in all CIN lesions, and staining intensity increased significantly with increasing severity of cervical intraepithelial lesions compared with non-neoplastic epithelium. All cervical squamous cell carcinoma had high staining intensity while adenocarcinoma and small cell carcinoma were stained negative. Conclusion: P63 can be used as a marker for the distinction between reactive cervicitis and cervical intraepithelial changes. It is also of value for grading of CIN lesions and differentiation between squamous cell carcinoma, adenocarcinoma, and small cell carcinoma.

P63+Krt5+ basal cells are increased in the squamous metaplastic epithelium of patients with radiation-induced chronic Rhinosinusitis

BackgroundSquamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls.MethodsWe assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36), CRSsNP (n = 33) and controls (n = 28).ResultsThe prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium.ConclusionSM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma.

Simple SummaryDifferent subtypes of lung cancer respond differently to treatment. To understand the signaling pathways that dictate the aggressive behavior of lung adenocarcinoma vs. lung squamous cell carcinoma, we performed a survival analysis that demonstrated that the protein Schlafen 12 correlates with better survival in patients with lung adenocarcinoma but not patients with lung squamous cell carcinoma, indicating specificity of the effect of the SLFN12 pathway in lung cancer subtypes. We investigated this specific effect by confirming the ability of Schlafen 12 to reduce cell proliferation of lung adenocarcinoma cells in vitro but not that of lung squamous cell carcinoma. Moreover, we demonstrated that Schlafen 12 acts through translational inhibition of c-myc protein in lung adenocarcinoma cells. The ability to delineate the exact signaling pathways that modulate each lung cancer subtype’s aggressive behavior will help in the future development of precision medicine to target this challenging disease.Schlafen 12 (SLFN12) is an intermediate human Schlafen that induces differentiation in enterocytes, prostate, and breast cancer. We hypothesized that SLFN12 influences lung cancer biology. We investigated survival differences in high versus low SLFN12-expressing tumors in two databases. We then adenovirally overexpressed SLFN12 (AdSLFN12) in HCC827, H23, and H1975 cells to model lung adenocarcinoma (LUAD), and in H2170 and HTB-182 cells representing lung squamous cell carcinoma (LUSC). We analyzed proliferation using a colorimetric assay, mRNA expression by RT-qPCR, and protein by Western blot. To further explore the functional relevance of SLFN12, we correlated SLFN12 with seventeen functional oncogenic gene signatures in human tumors. Low tumoral SLFN12 expression predicted worse survival in LUAD patients, but not in LUSC. AdSLFN12 modulated expression of SCGB1A1, SFTPC, HOPX, CK-5, CDH1, and P63 in a complex fashion in these cells. AdSLFN12 reduced proliferation in all LUAD cell lines, but not in LUSC cells. SLFN12 expression inversely correlated with expression of a myc-associated gene signature in LUAD, but not LUSC tumors. SLFN12 overexpression reduced c-myc protein in LUAD cell lines but not in LUSC, by inhibiting c-myc translation. Our results suggest SLFN12 improves prognosis in LUAD in part via a c-myc-dependent slowing of proliferation.

Clinicopathological and prognostic features of nasopharyngeal carcinoma in children and adolescents: A retrospective study of 196 cases in South China.

Nasopharyngeal carcinoma (NPC) occurring in children and adolescence is extremely rare and till present there is a lack of understanding on their clinicopathological and prognostic features of this rare entity. For our study, data of 196 cases children and adolescents with NPC from the past 18 years at a high-volume cancer center from South China were retrospectively analyzed. Half of the evaluated NPC patients (83/166, 50.0%) were staged as Stage IVa disease, whereas 1.2% (2/166), 27.7% (46/166), 16.9% (28/166) and 4.2% (7/166) had Stage II, III, IVb and IVc disease, respectively. Serum EBV EA-IgA ≥1:10 and VCA-IgA ≥1:40 were found in 67.7% (113/167) and 76.6% (128/167) of the evaluated patients, respectively, whereas 56.8% (84/148) of the patients had plasma EBV DNA ≥1000 copies/mL. Histologically, all tumors were classified as nonkeratinizing squamous cell carcinoma (NK-SCC). Immunohistochemistrically, the expression of CK (AE1/AE3), P63, CK5/6 and P40 were observed in 100% (88/88), 93.2% (68/73), 84.1% (58/69) and 63.2% (12/19) of the detected cases, respectively. All cases show similar immunophenotype compared to that occurring in adult patients. All evaluated cases (71/71 100%) harbored EBER. Patients with plasma EBV DNA ≥1000 copies/mL and positive serum EBV antibodies had significantly inferior 3-year OS (88% vs 100%, P = .007) compared to other corresponding groups. The combination of EBV serology and plasma EBV DNA are useful to predict the outcome of patients with NPC in children and adolescents.

Predictive markers for pathological complete response after neo-adjuvant chemotherapy in triple-negative breast cancer

A combination of Sox10 and GATA3 was previously identified as a marker for metastatic triple-negative breast cancer (TNBC), but it is uncertain whether their expression is associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). This study investigates the predictive value of clinicopathological characteristics, as well as protein expression of Sox10, GATA3, p53 and p63, in a consecutive series of TNBC patients treated with NAC.Archived hematoxylin & eosin stained slides of core biopsies and resection specimens from 35 TNBC patients were reviewed. The following clinicopathological characteristics were determined at the biopsy level: age at diagnosis, cancer type, Nottingham grade, lympho-vascular invasion, syncytial growth, necrosis, clear cell differentiation, myxoid peritumor stroma, stromal tumor-infiltrating lymphocytes (sTILs) and presence of an in situ component. The MD Anderson residual cancer burden (RCB) score and corresponding RCB class were determined. Immunohistochemistry for Sox10, p53, GATA3 and p63 was performed at the biopsy level.sTILs, either as a continuous or as a dichotomous variable, were the only parameter that was significantly associated with pCR in univariable and multivariable analyses. Assessment of sTILs showed moderate to good interobserver agreement. High sTILs (≥40%) were significantly associated with increased pCR rates, and this association was observer-independent.This retrospective study of a consecutive community-based cohort of TNBC patients confirms that sTILs are a robust, observer-independent predictor for therapeutic response after NAC. The combination of Sox10, GATA3 and p53 immunoreactivity is unlikely to harbor any predictive value for pCR in TNBC.

P63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma

Aimp63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association...

WITHDRAWN: Evaluation of expression of p63 and amelogenin in human tooth germ and ameloblastoma

BACKGROUND: The study was undertaken to evaluate the expression of p63 and amelogenin in human tooth germs and ameloblastomas by immunohistochemistry to find out whether the pattern of expression was related to differentiation of ameloblasts. MATERIALS AND METHODS: In this study fifteen human tooth germs of late bell stage, six human tooth germs of early bell stage and fifteen ameloblastoma samples were included and expression pattern of p63 and amelogenin were evaluated individually in all the samples. RESULTS: During the early bell stage, p63 expression was intense throughout the enamel organ. But, during the late bell stage, the number and intensity of p63 expression decreases in the cells of enamel organ. The peripheral cells in the ameloblastoma shows variable pattern of p63 expression. Expression of amelogenin was first evident in the presecretory ameloblasts at the cusp tip, followed by secretory ameloblasts and progresses cervically. But in ten late bell stage tooth germs, amelogenin expression was negative in the secretory ameloblasts and positive only at the secreting end i.e. tomes process. Intense staining was evident at the enamel matrix and in some dentinal tubules nearer to enamel matrix secretion. No amelogenin expression was evident in the dental papilla cells or odontoblasts throughout odontogenesis with the exception of dental follicle. Amelogenin expression was absent in eleven cases of ameloblastoma, but in four cases positive expression was evident at the peripheral cells. CONCLUSION: In the present study, the expression pattern of p63 and amelogenin in human tooth germ and ameloblastoma correlates with cytodifferentiation of ameloblasts.

Application of p16, p63, cyclin D1 immunostaining and nuclear morphometric analysis for assessment of cervical dysplasia

Background/Aim. Human papilloma virus (HPV) infection is the main etiological factor for the development of cervical precancerous dysplastic squamous intraepithelial lesions (SIL). The virus oncoproteins affect several proteins included in cell proliferation. The aim of this study was to evaluate application of immunohistochemical markers related to proteins of the cell cycle and, also, application of nuclear morphometric analysis for assessment of cervical dysplasia. Methods. Retrospective study included 78 women with detection of presence of high-risk HPV by polymerase chain reaction (PCR), with histopathology diagnosis low-grade SIL (LSIL) or high-grade SIL (HSIL). Immunohistochemical staining for p16, p63, cyclin D1 and morphometric analysis of the nuclear surface area were performed. The control group consisted of ten women without SIL and without HPV infection. This study was conducted in accordance with the Helsinki Declaration. Results. Comparing immunohistochemical expression of p16 and p63, highly statistically significant differences (p &lt; 0.001) were established among the control, LSIL and HSIL groups, while cyclin D1 showed significant statistical difference (p &lt; 0.05). Great variations were observed in nuclear morphology and nuclear surface area that had highly statistically significant differences (p &lt; 0.001) among the control, LSIL and HSIL groups. Conclusion. This study demonstrated that immunohistochemical analysis of p16, p63 and cyclin D1 are important for diagnosis of dysplastic changes in cervical epithelium. Also, morphometric analysis of the nuclear surface area demonstrated a high significance for diagnosis of cervical dysplasia.

MTOR plays a pivotal role in multiple processes of enamel organ development principally through the mTORC1 pathway and in part via regulating cytoskeleton dynamics

We herein report that deletion of mTOR in dental epithelia caused defective development of multiple cell layers of the enamel organ, which culminated in tooth malformation and cystogenesis. Specifically, cells of the stellate reticulum and stratum intermedium were poorly formed, resulting in cystic changes. The pre-ameloblasts failed to elongate along the apical-basal axis and persisted vigorous expression of Sox2 and P63, which are normally downregulated during cytodifferentiation. Expression of amelogenic markers was also attenuated in mutants. Cell proliferation and cell sizes in mutants were significantly reduced over time. Importantly, we found reduced amounts and aberrant aggregations of cytoskeletal components in mutants, along with attenuated expression of cytoskeleton regulator Cdc42, whose epithelial deletion causes a similar phenotype. Moreover, disruption of actin assembly in an organ culture system affected cell proliferation and cytodifferentiation of tooth germs, supporting a causative role of mTOR-regulated cytoskeleton dynamics for the observed phenotype of mTOR mutant mice. In further support of this view, we showed that mTOR overactivation caused increased cytoskeletal component synthesis and assembly, along with accelerated cytodifferentiation in the enamel organ. Finally, we demonstrated that mTOR regulated enamel organ development principally through the mTORC1 pathway.

Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

Histone Deacetylase 1 and Sirtuin 1 Expression in Psoriatic Skin: A Comparison between Guttate and Plaque Psoriasis.

Abnormal histone modification by histone deacetylases (HDACs), including HDAC1 and sirtuin 1 (SIRT1), has been reported to play an important role in the pathogenesis of psoriasis by altering cell proliferation, differentiation, and inflammation. However, findings on the expression level of HDACs in psoriatic skin lack consistency. We assessed the expression of HDAC1, SIRT1, p63, and proliferating cell nuclear antigen (PCNA) in skin tissues from 23 patients with psoriasis (15 with plaque psoriasis and eight with guttate psoriasis) and five healthy individuals using immunohistochemistry, and analyzed their associations with clinical phenotypes of the disease. The expression of HDAC1 and keratinocyte proliferative markers, such as p63 and PCNA significantly increased, whereas that of SIRT1 decreased in the basal layer (p < 0.05) of the patients with psoriasis compared to those in healthy controls. Among the patients with psoriasis, expression of HDAC1, p63, and PCNA was significantly higher in plaque psoriasis than in guttate psoriasis. There was no significant differences in the level of SIRT1 between the two clinical phenotypes. The findings of this study suggest that histone modifications are involved in the pathogenesis of psoriasis and may contribute to the formation of clinical phenotypes.

ΔNp63 is upregulated during salivary gland regeneration following duct ligation and irradiation in mice.

The transcription factor p63, a component of the p53 family, has important functions in development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of ΔNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, ΔNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that ΔNp63 is essential for SG regeneration and may be a new target for regenerative treatment.

Keratinocyte growth factor signaling promotes stem/progenitor cell proliferation under p63 expression during middle ear cholesteatoma formation.

Middle ear cholesteatoma is an epithelial lesion that expands into the middle ear, resulting in bone destruction. However, the pathogenesis of this has been unknown. The purpose of this review is to understand the role of keratinocyte growth factor (KGF) during epithelial stem and/or progenitor cell proliferation in middle ear cholesteatoma. Many researchers have investigated the molecular mechanism of middle ear cholesteatoma to establish a conservative treatment. Recently, some studies have focused on the stem cells of middle ear cholesteatoma and their detection, but the key molecules for stem cell formation were not shown. We established an animal model for middle ear cholesteatoma and are showing the results of our studies. KGF expression accelerates the proliferation of stem/progenitor cells through the induction of transcription factor p63 expression in the epithelium of the tympanic membrane and mucosal epithelium overlying the promontory of the cochlea and within the attic. This is typical in middle ear cholesteatoma. Moreover, the partial epithelial-mesenchymal transition under the p63 signaling pathway plays an essential role in epithelial cell growth in middle ear cholesteatoma formation. Understanding p63 expression following KGF expression and associated signaling events can improve therapeutic outcomes in patients with middle ear cholesteatoma.

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature

The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only.

Notch activation leads to loss of myoepithelial differentiation and poor outcome in solid adenoid cystic carcinoma.

We aimed to investigate Notch pathway dysregulation in solid adenoid cystic carcinoma (AdCC) and to define the association of Notch activation with cell differentiation and prognosis in AdCCs. Notch1 mutations were detected from 125 AdCCs (62 cribriform-tubular; 63 solid). RNA-seq was performed in 16 AdCCs (6 Notch-mutant; 10 wild type). Notch activation indicator NICD and myoepithelial marker p63 were detected using immunohistochemistry and double-labelling immunofluorescence. The effect of exogenous NICD overexpression on p63 expression and cell proliferation was investigated using Western blotting and live-cell imaging. We identified 33 Notch1 activating mutations in 27 AdCCs including 26 solid and 1 cribriform-tubular subtypes. Six tumours harboured more than one Notch1 mutation, and 18 Notch1 mutations were novel. Most (47/63, 74.6%) solid AdCCs showed NICD overexpression, whereas 61 of 62 (98.4%) cribriform-tubular tumours were negative. NICD and p63 exhibited mutually exclusive expression, and exogenous NICD overexpression promoted cell proliferation and decreased p63 expression. NICD overexpression and Notch mutations were poor indicators for overall survival and metastasis, especially bone metastasis. Dysregulated Notch signalling plays a critical role in AdCC severity. Notch activation may contribute to loss of myoepithelial differentiation as well as high proliferation and metastasis rates in solid AdCC.

Clinicopathological correlation of p63 in Urothelial Carcinoma: Immunohistochemical Study

Background: Urothelial cancer (UCa) poses a significant medical and public health concern in most parts of the world and is defined as a pan- urothelial disease in which entire urothelium of the renal pelvis to the urethra can undergo malignant transformation. Bladder tumors account for 90–95% of urothelial carcinomas and are the most common urinary tract malignancy. It is three times less common in females.&#x0D; Methods: The study was conducted on 40 cases of Urothelial Carcinoma received as biopsy specimens in a tertiary care hospital. There were 20 cases each of low grade and high grade and after grading these were subjected to p63 expression.&#x0D; Result: 78% of the patients were from 50-75 year age group with Male to Female ratio being 4:1. Painless hematuria was most common complaint. The size varied from 0.5 to 7.2 cm.&#x0D; For P63, 38 (95%) cases showed positive p63 expression. Of which 20 cases were low grade and 18 (90%) were high grade papillary urothelial carcinomas. Of P63 positive cases 36 cases showed moderate to strong staining intensity whereas two cases showed mild staining intensity. The p63 expression decreased with grade and invasion.&#x0D; Conclusion: P63 immunoexpression decreases with increasing grade of tumor as well as with invasion thus showing that its expression is related with good prognosis.

KLF3 Mediates Epidermal Differentiation through the Epigenomic Writer CBP.

SummaryImpairments in the differentiation process can lead to skin diseases that can afflict ∼20% of the population. Thus, it is of utmost importance to understand the factors that promote the differentiation process. Here we identify the transcription factor KLF3 as a regulator of epidermal differentiation. Knockdown of KLF3 results in reduced differentiation gene expression and increased cell cycle gene expression. Over half of KLF3's genomic binding sites occur at active enhancers. KLF3 binds to active enhancers proximal to differentiation genes that are dependent upon KLF3 for expression. KLF3's genomic binding sites also highly overlaps with CBP, a histone acetyltransferase necessary for activating enhancers. Depletion of KLF3 causes reduced CBP localization at enhancers proximal to differentiation gene clusters, which leads to loss of enhancer activation but not priming. Our results suggest that KLF3 is necessary to recruit CBP to activate enhancers and drive epidermal differentiation gene expression.