Dysplasia Specimens Research Articles

Lower Prevalence of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma in Middle Eastern Population: Clinical Implications for Diagnosis and Prevention.

Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The prevalence of human papillomavirus (HPV) in HNSCC varies across regions. Objective This study aimed to determine the prevalence of high-risk HPV (hrHPV) among patients with HNSCC in the Middle East region. Methods Samples from patients with oropharyngeal or laryngeal lesions who underwent biopsy or resection at a tertiary care hospital from 2010 to 2015 were collected.Those confirmed as squamous cell carcinoma (SCC) on histopathology were identified as cases (n = 61), whereas benign lesions were used as controls (n = 83). Immunohistochemistry (IHC) for p16, p53, Ki-67, and in situ hybridization (ISH) for hrHPVgenotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66 were performed on all cases. Results A total of 154 cases were studied: 61 squamous cell cancers (cases), 83 benign lesions (control), and 10 dysplasia specimens. Among the cases, only five (8.6%) were positive for hrHPV, whereas only one control specimen tested positive.The SCC group had higher mean age, male sex, and history of cigarette smokingand alcohol usage. Among the hrHPV-positive SCC cases, 80% had a tumor in the oropharyngeal region. All hrHPV-positive cases were positive for p16 and p53 immunostains. Conclusion Among HNSCC cases, hrHPV was detected at a lower rate compared to other regions of the world. This study suggests that hrHPV plays a minor role in the pathogenesis of HNSCC in this region, compared to tobacco use and alcohol consumption.

Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study.

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.

Deep-learning application for identifying histological features of epithelial dysplasia of tongue

ObjectiveThis study aimed to evaluate the potential of artificial intelligence (AI) methods for histopathological grading of tongue dysplasia. MethodsA dataset comprising 203 digitized whole-slide images (WSIs) was constructed at 200× magnification from surgical specimens of tongue dysplasia and early cancers. Transfer learning was performed using this dataset with the convolutional neural network Inception-v3. Three experiments were conducted to (1) evaluate the potential of Inception-v3 by developing an AI system for epithelium classification and four AI systems for dysplasia grading (DysAI-1s), (2) compare the prediction performance of four DysAI-1s with that of humans, and (3) augment datasets to improve the accuracy of the developed AI system for dysplasia grading. ResultsThe area under the receiver operating characteristic curve (AUC) for epithelium classification was 0.996, while the average AUC scores of the four DysAI-1s were 0.921, 0.919, 0.867, and 0.774. In comparison, each AI system exhibited a moderate to substantial match (kappa, κ = 0.55−0.78) with the corresponding human predictions. The mean absolute errors (MAEs) showed a similar trend; MAEs of the DysAI-1s were 0.308, 0.403, 0.422, and 0.622. The final AI system (DysAI-2s) trained with larger datasets for dysplasia grading achieved an average κ-value of 0.81 despite different data-subset distribution ratios. Most MAEs of DysAI-2s showed better values than those of DysAI-1.1 (P < .001). ConclusionA properly trained AI system has the potential to improve the accuracy of oral dysplasia grading on WSIs.

Accurate Detection of Hot-Spot MTOR Somatic Mutations in Archival Surgical Specimens of Focal Cortical Dysplasia by Molecular Inversion Probes.

Formalin-fixed, paraffin-embedded brain specimens are a potentially rich resource to identify somatic variants, but their DNA is characterised by low yield and extensive degradation, and matched peripheral samples are usually unavailable for analysis. We designed single-molecule molecular inversion probes to target 18 MTOR somatic mutational hot-spots in unmatched, histologically proven focal cortical dysplasias from formalin-fixed, paraffin-embeddedtissues of50 patients. We achieved adequate DNA and sequencing quality in 28 focal cortical dysplasias, mostly extracted within 2years from fixation, showing a statistically significant effect of time from fixation as a major determinant for successful genetic analysis. We identified and validated seven encompassing hot-spot residues (foundin14% of all patients and in25% ofthose sequenced andanalysed). The allele fraction had a range of 2-5% and variants were absent in available neighbouring non-focal cortical dysplasia specimens. We computed an alternate allele threshold for calling true variants, based on an experiment-wise mismatch count distribution, well predicting call reliability. Single-molecule molecular inversion probes are experimentally simple, cost effective and scalable, accurately detecting clinically relevant somatic variants in challenging brain formalin-fixed, paraffin-embedded tissues.

Evaluation of CD24 and CD44 as cancer stem cell markers in squamous cell carcinoma and epithelial dysplasia of the oral cavity by q- RT-PCR

Squamous cell carcinoma (SCC) is the most common cancer of the oral cavity and may be preceded by dysplastic epithelial lesion. Oral SCC (OSCC) contains a rare subset of cancer cells with self-renewal ability, termed as cancer stem cells (CSCs). CD24 and CD44 as CSC markers are cell surface glycoproteins. These markers contribute to the onset, maintenance, and extension of tumor growth, as well as angiogenesis. In the present study, these two markers were simultaneously evaluated to provide a specific phenotype for carcinogenesis process in oral cavity. In this analytical-cross-sectional study, the expression of CD24 and CD44 genes was evaluated in 45 OSCCs (20 low-grade and 25 high-grade) and 15 oral epithelial dysplasia specimens by real-time quantitative reverse transcription polymerase chain reaction. Kruskal-Wallis and Mann-Whitney U-test, Kendall, and Spearman tests were used for statistical analysis. The significance level was considered <0.05. High expression of both markers genes was reported in two-thirds of samples. There was no significant difference between studied groups in gene expression of CD24 and CD44 whereas statistically significant association between CD24 and CD44 was observed in all three groups. This correlation was more significant in OSCC groups (P < 0.001). High expression of CSC markers in OSCC and oral epithelial dysplasia revealed the importance of accurate examination of dysplastic lesions with high expression of these markers and the possibility of malignant transformation. Regarding a significant association of two markers, further studies are necessary to provide a specific phenotype (CD44 high CD24 high) for these lesions.

Identification of Tumor Specific Peptide as EpCAM Ligand and Its Potential Diagnostic and Therapeutic Clinical Application.

Tumor targeting agents are being developed for early tumor detection and therapeutics. We previously identified the peptide SNFYMPL (SNF*) and demonstrated its specific binding to human esophageal specimens of high-grade dysplasia (HGD) and adenocarcinoma with imaging ex vivo. Here, we aim to identify the target for this peptide and investigate its potential applications in imaging and drug delivery. With SNF* conjugated affinity chromatography, mass spectrum, Western blot, enzyme-linked immunosorbent assay (ELISA), and molecular docking, we found that the epithelial cell adhesion molecule (EpCAM) was the potential target of SNF*. Next, we showed that FITC-labeled SNF* (SNF*-FITC) colocalized with EpCAM antibody on the surface of esophageal adenocarcinoma cells OE33, and SNF*-FITC binding patterns significantly changed after EpCAM knockdown or exogenous EpCAM transfection. With the data from TCGA, we demonstrated that EpCAM was overexpressed in 17 types of cancers. Using colon and gastric adenocarcinoma cells and tissues as examples, we found that SNF*-FITC bound in a pattern was colocalized with EpCAM antibody, and the SNF* binding did not upregulate the EpCAM downstream Wnt signals. Subsequently, we conjugated SNF* with our previously constructed poly(histidine)-PEG/DSPE copolymer micelles. SNF* labeling significantly improved the micelle binding with colon and gastric adenocarcinoma cells in vitro, and enhanced the antitumor effects and decreased the toxicities of the micelles in vivo. In conclusion, we identified and validated SNF* as a specific peptide for EpCAM. The future potential use of SNF* peptide in multiple tumor surveillance and tumor-targeted therapeutics was demonstrated.

Ki-67 Prognostic Value in Different Histological Grades of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Introduction:Abnormal cell proliferation appears to be a possible predictor of tumorigenesis, Ki-67 protein expression is closely related to the cell proliferation and could be used as a biomarker for the growth in the most of human tumors. The aim of the study: Investigating of Ki-67 expression in the pathological grades of oral epithelial dysplasia and oral squamous cell carcinomas.Materials and Methods:The sample consisted of 30 formalin-fixed, paraffin-embedded specimens of oral epithelial dysplasia (OED), 30 other of oral squamous cell carcinomas (OSCC), and 10 normal oral epithelium (NOE) were conventionally stained with hematoxylin and eosin and immunohistochemically stained with Ki-67 monoclonal antibody.Results:Expression of Ki-67 was restricted to the basal layers in the normal oral epithelium whereas Ki-67 positive cells in oral epithelial dysplasia (OED) were located in the basal, suprabasal and spinous layers, Ki-67 expression was increased in high-risk cases. Ki-67 positive cells in well-differentiated (OSCC) were located mainly in the periphery of the tumor nests, in moderately-differentiated (OSCC) were located in both peripheral and part of a center of the tumor nests whereas it was diffused in most of the Poorly-differentiated (OSCC). Statistical analysis indicated a significant difference between the expression in (OED) and (NOE), (OSCC) and (NOE), and no differences between (OED) and (OSCC).Conclusion:This study has concluded that Ki-67 antigen could be used as a marker for the histological grading of OED and OSCC, Expression of Ki 67 increased according to the severity of oral epithelial dysplasia.

Quantitative analysis of protocadherin 10 promoter methylation in peripheral blood of patients with gastric cancer by real-time and methylation specific polymerase techniques and its significance

Objective To investigate protocadherin 10 (PCDH10) methylation at promoter 5’-cytosine-phosphoric acid-guanine motif (CpG) island as a tool for non-invasive diagnosis and prognosis evaluation of primary gastric cancer. Methods Real-time fluorescent quantitative methylation specific polymerase chain reaction (Real-time MSP) technique was used for detection of PCDH10 promoter methylation in both tissue and serum specimens from 202 gastric cancer (GC), 52 gastric epithelial dysplasia, and 68 chronic gastritis, as well as 120 healthy human serum specimens. The relationship between PCDH10 methylation with clinicopathological parameters and prognosis was analyzed. Results The incidence of PCDH10 methylation in gastric cancer tissues (80.2%, 162/202) was significantly higher than that in paired adjacent tissues (26.7%, 54/202), gastric epithelial dysplasia (23.1%, 12/52) and chronic gastritis specimens (14.7%, 10/68) (all P=0.000). Detectable rate of PCDH10 methylation in serum specimens was in good agreement with that in the paired tumor tissues, with the Aζ value being 0.862 (P=0.000). The level of PCDH10 methylation in serum was closely correlated to age at diagnosis (P=0.018), H. pylori (Hp) infection (P=0.000), tumor size (P=0.000), tumor differentiation (P=0.002), lymphatic invasion (P=0.000), venous invasion (P=0.007), invasion depth (P=0.000), lymphatic metastasis (P=0.000), distant metastasis (P=0.015), clinical stages (P=0.000) and poor prognosis (P=0.000), but not with gender (P=0.435), tumor site (P=0.458) and growth pattern (P=0.435). Conclusion PCDH10 methylation plays an important role in the tumorigenesis and development of gastric cancer. Key words: Gastric cancer; Protocadherin 10; DNA methylation; Early diagnosis; Prognosis

A mouse model of DEPDC5-related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5flox/flox-Syn1Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions.

Immunohistochemical expression of pericytes and myofibroblasts in the extracellular matrix of oral actinic cheilitis and squamous cell carcinoma: a comparative study

OBJECTIVE: The aim of the present study is to conduct a comparative analysis of oral actinic cheilitis and squamous cell carcinomas by immunohistochemical analysis.METHODS: This cross-sectional study utilizes a convenience sample obtained from the archives of an oral pathology laboratory from a higher education institution. Tissue sections from patients diagnosed with actinic cheilitis and carcinoma were immunohistochemically analyzed using monoclonal antibodies specific for smooth muscle alpha actin (SMA) and neuron-glial antigen 2 (NG2). Individual cells that stained positive for these proteins were counted in specific fields by means of histomorphometry.RESULTS: Subsequent statistical analysis revealed a higher number of NG2-positive when compared with SMA-positive cells in both lesion types (p = 0.005) and these cells were located adjacent to blood vessels. The differences between normal oral mucosa, severe dysplasia, and carcinoma specimens were statistically significant (p = 0.009; p = 0.006).CONCLUSION: These data strongly suggest that increased expression of NG2- and SMA-positive cells is associated with formation of blood capillaries, highlighting the importance of angiogenesis in tumor progression.

Bit1 Regulates Cell Migration and Survival in Oral Squamous Cell Carcinoma

Increasing evidence has shown that Bcl-2 inhibitor of transcription 1 (Bit1) involves a variety of biological processes in the process of tumor development and progression. We hypothesized that Bit1 would be overexpressed in oral squamous cell carcinoma (OSCC); therefore, we examined Bit1 gene expression and protein production, as well as explored the effect of elevated Bit1 levels on OSCC cells. We investigated the use of quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry analysis for Bit1 messenger RNA and protein levels.We used 75 OSCC specimens, 25 tumor-adjacent dysplasia specimens, and 25 normal oral tissue samples that matched OSCC specimens in this study. We also transfected Bit1 complementary DNA into human oral cancer cells (Tca8113) to further investigate the potential role of Bit1 in OSCC. We found that Bit1 levels in OSCC tissues were significantly higher than those in tumor-adjacent dysplasia specimens and normal oral tissue (P<.05). We also confirmed that Bit1 overexpression in the cytosol of Tca8113cells induced apoptosis. Our findings suggest Bit1 overexpression may contribute to oral cancer cell survival and dissemination. In the future, Bit1 may be an important diagnostic and therapeutic target.

Multimodal fiber-probe spectroscopy allows detecting epileptogenic focal cortical dysplasia in children.

We evaluated the diagnostic capability of a multimodal spectroscopic approach for classifying normal brain tissue and epileptogenic focal cortical dysplasia in children. We employed fluorescence spectroscopy at two excitation wavelengths (378 nm and 445 nm) and Raman spectroscopy (at 785 nm excitation) for acquiring fluorescence and Raman spectra from 10 normal brains, 16 focal cortical dysplasia specimens and 1 cortical tuber tissue sites using a custom-built multimodal optical point spectroscopic system. We used principal component analysis combined with leave-one-sample-out-cross-validation for tissue classification. The study resulted in 100% sensitivity and 90% specificity using the information obtained from fluorescence at two distinct wavelengths and Raman spectroscopy for discriminating normal brain tissue and focal cortical dysplasia. Our results demonstrate that this methodology has the potential to be applied clinically for the detection of focal cortical dysplasia and can help to improve as precise as possible surgical resection of the dysplastic tissue during surgery for epilepsy. Schematic draw of the experimental setup used for fiber-probe spectroscopy.

Immunohistochemical Expression of p53 and Ki-67 Genes in Gastric Cancer and Precancerous Lesions in the Patients with Helicobacter pylori Infection

Background: Helicobacter pylori (H. pylori) infection is considered as a carcinogen for gastric mucosa. The mechanism by which H. pylori are involved in gastric carcinogenesis is still unclear. Objectives: The current study aimed to investigate the effects of H. pylori infection on immunohistochemical expression of p53 and Ki-67 genes in gastric specimens of patients with intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC). Methods: In the study, 42 cases with IM, 38 with DYS and 42 with GC were selected from pathology archive of Ali-ebne-Abitaleb hospital, Zahedan, Iran; p53 and Ki-67 immunohistochemical study was done, accordingly. Kruskal-Wallis and Mann-Whitney U tests were used to compare the groups. Level of significance was set at P < 0.05. Results: In IM specimens, expression of p53 and Ki-67 was significantly higher in the cases with H. pylori infection than those not infected with H. pylori. In DYS specimens, in the group with H. pylori infection, the expression of p53 was significantly higher while expression of Ki-67 was significantly lower than the group without H. pylori infection. In GC specimens, the expression of p53 was significantly higher in the group with H. pylori infection compared to the group without H. pylori infection. Expression of Ki-67 in the specimens with H. pylori infection was not significantly different from those without H. pylori infection. Conclusions: The study results showed that p53 expression increased in IM, DYS and GC cases with H. pylori infection compared to those without H. pylori infection. The results also suggested that, Ki-67 expression was different in precancerous stages of gastric carcinogenesis, based on the infection with H. pylori.

Assessment of Bacterial Profile of Osteonecrosis in Jaw Due to Biphosphonate Use

Germany; University of Cologne, Faculty of Medicine, Institute for Pathology, Cologne, Germany Objective: The current study has been undertaken to assess the potential role of p16 and Ki-67 expression in human papilloma virus (HPV) related oral, tonsillary and laryngeal lesions. Study Design: This study was conducted on 71 specimens of oral, tonsillary and laryngeal lesions with 25 dysplasia and 46 papilloma specimens. Specimens were immunohistochemically stained for p16 and Ki-67 proteins. HPV DNA was determined by one step multiplex PCR. Results: HPV DNA was detected in 33.8% of all lesions. Tonsil and larynx lesions showed significant difference with oral lesions for HPV positivity. p16 over-expression was seen in 56.5% of papilloma and 60% of dysplasia specimens. Dysplasia specimens displayed higher proliferation index than papillomas. Conclusions: p16 expression may have a value in HPV induced dysplasia lesions. Proliferation index is not related to HPV induced lesions and may be evaluated as an independent marker in dysplastic lesions.

The use of CA-IX as a diagnostic method for oral leukoplakia

The presence and degree of dysplasia are important diagnostic and prognostic criteria for oral leukoplakia, but evaluation of dysplasia is difficult and subjective. Carbonic anhydrase-IX (CA-IX) is expressed primarily in tumor cells and is considered a specific hypoxia marker. We investigated the role of CA-IX in oral leukoplakia. We investigated 30 specimens of oral leukoplakia and 35 dysplasia specimens adjacent to the tumor margin. We analyzed clinical variables including age, sex, degree of dysplasia, and smoking, clinical appearance of leukoplakia, number of lesions, location, size, clinical monitoring, malignant transformation and recurrence. For the immunohistochemical study, we used a noncommercial monoclonal antibody against human CA-IX MAb M75. We found greater CA-IX positivity in nonsmokers, erythroplakia and mottled leukoplakia, those located on the tongue, patients with multiple lesions, 2–4 cm leukoplakias and in recurrent cases, although differences were not statistically significant. All lesions in all samples without dysplasia were negative for CA-IX; however, for all other categories of dysplasia, the percentages of positivity and negativity varied. Regarding the diagnostic index values, we found a sensitivity of 32%, specificity of 100%, a positive predictive value of 100% and a negative predictive value of 13%. Leukoplakias appear mainly in females and potentially are malignant; more than 90% have some degree of dysplasia, and therefore require close clinical and histopathological monitoring. The CA-IX immunohistochemical marker may be useful for screening samples without dysplasia owing to its high specificity.

HPV in HIV-Infected Women: Implications for Primary Prevention.

Background: There is growing evidence that human immunodeficiency virus (HIV)-infected women might have a different human papillomavirus (HPV) type distribution in cervical dysplasia specimens as compared to the general population. This has implications for primary prevention.Objective: We aimed to obtain preliminary data on the HPV genotypes prevalent in histological samples of HIV-infected women with cervical intraepithelial neoplasia (CIN) 3/CIS of the cervix in Miami, FL, USA.Methods: Retrospective data were collected on HIV-infected women referred to the University of Miami-Jackson Memorial Hospital colposcopy clinic between years 2000 and 2008. The histology slides of CIN 3/CIS biopsies underwent pathological review and sections were cut from these archived specimens for HPV DNA extraction. HPV genotyping was then performed using the GeneSquare™ HPV genotyping assay. We report on our first set of 23 samples.Results: Eight high-risk HPV types were detected. Types in decreasing order of frequency were 16, 35, 45, 52, 59, 31, 58, and 56. Most cases had multiple infections. HPV type 16 was the most common (45%) followed by HPV-35 and -45 with equal frequency (40%). No samples contained HPV-18.Conclusion: Our preliminary results suggest that cervical dysplasia specimens of HIV-infected women more likely (55%) contain non-16 and -18 high-risk HPV types. We show that this held true for histologically confirmed severe dysplasia and carcinoma-in situ. Epidemiological studies guide vaccine development, therefore HPV type prevalence in CIS and invasive cervical cancer among HIV-infected women should be more rigorously explored to ensure that this highly vulnerable population receives appropriate primary prevention.

Expressions of NF-B and TFF3 in gastric cancer and its clinical significance

Objective To study the expressions and correlation of nuclear factor kappa B （ NF-B） p65 and trefoil factor family-3（TFF3） in gastric cancer,in order to evaluate the roles of NF-Bp65 and TFF3 in the occurrence and development of gastric cancer,and their correlation with Helicobacter pylori （Hp） infection.Methods The expressions of NF-Bp65 and TFF3 were detected by immunohistochemistey in 30 normal gastric mucosa specimens ,32 dysplasia specimens and 70 gastric cancer specimens .At the same time,the infection of Hp was detected .Results In normal gastric mucosa ,dysplasia and gastric cancer ,the expression of NF-Bp65 had a increasing tendency （ compared with the normal gastric mucosa group ,χ^2 =18.632,44.291,all P〈0.01）.The expression of NF-Bp65 in gastric cancer group was higher than that in dysplasia group （χ^2 =5.205,P〈0.05）.The expression of TFF3 in three groups also had a increasing tendency （compared with the normal gastric mucosa group ,χ2 =16.944,22.917,all P 〈0.01）.The expression of TFF3 in gastric cancer group was higher than dysplasia group ,but there was no significant difference between the two groups （χ^2 =0.162,P〉0.05）.In dysplasia group,the expressions of TFF3 and NF-κBp65 in Hp positive patients were significantly higher than those in Hp negative patients （P〈0.01 or P〈0.05）.There was significantly positive correlation between expression of NF-Bp65 and TFF3 in gastric cancer group （ r=0.350,P=0.003）.Conclusion High expressions of NF-Bp65 and TFF3 may be involved in an early event of gastric cancer . NF-Bp65 expression is positively correlated with the abnormal expression of TFF 3,both of which may be involved in the development and progression of gastric cancer . Key words: Stomach neoplasms; Transcription factors

Laryngeal Papillomatosis Associated Dysplasia in the Adult Population

The objectives were to determine the prevalence of laryngeal dysplasia and associated human papilloma virus (HPV) subtypes in adult patients, 18 years or older, suffering from laryngeal papillomatosis at a tertiary care institution. Retrospective cohort study. Patients with biopsy proven laryngeal papillomatosis were identified via chart review. All available pathology specimens were reviewed by a dedicated head and neck pathologist to confirm/refute the diagnosis of laryngeal dysplasia, and grade the level of dysplasia. Interrater agreement was compared using cross-tabulation methods. Specimens identified to be positive for dysplasia underwent further testing via in situ hybridization for low-risk (6/11) or high-risk (16/18) HPV subtypes. Of the 85 subjects identified to have laryngeal papillomatosis, 24(28%) demonstrated laryngeal dysplasia. There was good interrater agreement on the presence of dysplasia; however, there was only fair agreement on the grade of dysplasia. Of the pathology specimens tested for HPV subtype, the majority of patients (62%) were positive for HPV 6/11, including all high-grade dysplasia patients. Three (12%) dysplasia specimens were negative for both high- and low-risk HPV subtypes. We found a 28% prevalence of dysplasia in our patient population with the majority of patients positive for low-risk HPV subtypes indicating that high-risk HPV subtypes do not predispose laryngeal papilloma patients to dysplasia.

Immunohistochemical staining patterns of cytokeratins 13, 14, and 17 in oral epithelial dysplasia including orthokeratotic dysplasia

Diagnosis of the exact grade of oral epithelial dysplasia is difficult, and interobserver variations in grading are common. The aim of this study was to investigate the expression patterns of cytokeratins (CKs) in dysplastic oral epithelia, to identify useful double immunostaining diagnostic markers. Immunoexpression of CK13, CK14, CK17, and Ki-67 were investigated in 21 normal epithelial specimens and 146 epithelial dysplasia specimens. In epithelial dysplasia specimens, orthokeratotic dysplasia (OKD) was identified using CK10 immunostaining. Most mild dysplasia specimens were CK13+ and CK17-. In moderate dysplasia, CK13 expression tended to be lower and CK17 expression tended to be higher than in mild dysplasia. All carcinoma in situ (CIS) specimens were CK17+. In differentiated type CIS specimens, CK13 expression was weakly positive. Most epithelial dysplasia specimens were CK14+. There were no significant differences in the expression patterns of CKs between OKD and non-OKD specimens in any of the grades of dysplasia. These results indicate that CK14 expression can be used to detect early epithelial dysplasia, and that CK13 and CK17 expression are useful for detecting neoplastic changes.

PITX1 is a reliable biomarker for predicting prognosis in patients with oral epithelial dysplasia

Paired-like homeodomain 1 (PITX1) genes are essential in human development. In the present study, PITX1 protein expression was evaluated in human normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC), with the aim of examining the expression patterns of these critical genes during the multi-stage transformation of oral epithelial dysplasia to OSCC. PITX1 and Ki-67 expression were assessed by immunohistochemistry in 26 individuals with normal oral mucosa, 106 patients with oral epithelial dysplasia and 97 OSCC patients. The labeling indices (LIs) of PITX1 and Ki-67 were calculated and their correlation with the incidence of malignancy was evaluated. The PITX1 LI of the dysplasia specimens was significantly lower than that of the normal oral mucosa samples, but significantly higher than that of the OSCC samples. The oral epithelial dysplasia patients that exhibited low PITX1 expression showed a significantly higher incidence of malignant transformation than those exhibiting high PITX1 expression, regardless of the histological grades of their oral epithelial dysplasias. On the other hand, no correlation was observed between the Ki-67 LI and the incidence of malignancy. These results suggested that PITX1 suppression is associated with malignant transformation in the oral epithelium and that PITX1 expression may serve as a novel biomarker for predicting prognosis in oral epithelial dysplasia.