Dysplastic Epithelial Cells Research Articles

Abstract 2170: Effects of folic acid supplementation on early stages of colitis-associated carcinogenesis

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by persistent mucosal inflammation extending throughout the colon. Due to compromised intestinal surface integrity and the prolonged use of medication, individuals with UC often develop a folate deficiency, requiring folic acid (FA) supplementation. Prior findings from this group indicate that FA supplementation, at clinically relevant levels, promotes UC-associated dysplasia. Supplementation with FA resulted in an increased multiplicity of dysplasia and a significant elevation in the expression of several inflammatory genes (e.g. IL-6, Cox-2, Iκκ-β) within the colonic mucosa of mice with UC. Genome-wide expression profiling of normal and dysplastic colonic epithelial cells from mice treated with different doses of FA revealed differentially expressed genes were enriched for members of the ERK and NF-κB pathways. Subsequent in vitro analyses, utilizing isogenic RKO colon adenocarcinoma cells exposed to various doses of FA, demonstrated the downregulation of ERK and p-ERK in wild type (WT) p53+/+ cells, while an increase in expression was observed in p53−/− cells at the protein level. The goal of this study is to investigate the role of the MAPK/ERK pathway in the development of UC-associated neoplasms. An in vitro model that faithfully reproduces the inflamed microenvironment in the context of WT vs. mutant p53, the putative gatekeeper of UC-associated carcinogenesis, is needed to enhance our understanding of early changes in the colon that are induced by FA and drive tumor formation. Colon organoids are being generated by isolating crypts from WT p53+/+ and mutant p53+/515A mice. These organoids are then co-cultured with mouse macrophages (RAW264.7 cells) in inserts to stimulate crosstalk between the macrophages and colonic epithelial cells, as in the inflamed colon. Analyses demonstrate that the macrophages express pivotal inflammatory cytokines characteristic of UC, including IL-1β, IL-10, TNF-α, and IL-6, irrespective of the presence or absence of LPS stimulation. Co-cultured organoids and macrophages will be exposed to different concentrations of FA for various lengths of time, and the impact of treatment on the levels of ERK, p-ERK, and p65 will be assessed. The ability of p-ERK to mediate the transcriptional activation of NF-κB and its downstream effector IL-6 will also be evaluated. Subsequent investigations employing this innovative experimental model will reveal the mechanisms by which FA supplementation promotes the progression of UC-associated dysplasia. Given the potential risks associated with FA supplementation in individuals with UC, there is an urgent need to translate these results to a clinical setting. (Supported by CA262551 and the Timothy and Aurora Hughes Cancer Research Fund). Citation Format: Ariane Rocha Bartolomeu, Wen-Chi Chang, Lisa Vanderveer, Kristen N. Harvey, Mitchell Cheung, Harry S. Cooper, Margie Lee Clapper. Effects of folic acid supplementation on early stages of colitis-associated carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2170.

Differences in circulating lymphocyte subpopulations among patients with inflammatory polyps, colorectal adenomas and colorectal cancer

Background and Study AimsColorectal cancer (CRC) may develop from focal changes within benign or precancerous polyps. The immune system’s failure to detect and eradicate tumor cells due to immune surveillance evasion, allows cancer to develop and spread. This study aims to analyze the differences in circulating lymphocyte subpopulations in patients with colorectal inflammatory polyps, colorectal adenomas and CRC. Patients and MethodsWe retrospectively reviewed patients from September 2016 to December 2019 at the Shaoxing Second Hospital. Using flow cytometry, the subset distribution and immunophenotype of T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells were investigated in peripheral blood mononuclear cell samples. The counts of lymphocytes were determined by white blood cell counts. ResultsIn total, 518 patients were included in this study. The counts of lymphocytes, T cells and NK cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts and percentages of CD8+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts of CD4+ T cells were lower in patients with CRC than inflammatory polyps. The percentages of CD4+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were higher than controls, but lower in the CRC than inflammatory polyps, colorectal adenomas. The counts and percentages of B cells were lower in CRC patients than colorectal adenomas patients. In addition, the percentages of B cells were higher in patients with inflammatory polyps and colorectal adenomas than in controls. ConclusionsThe decrease in counts of lymphocyte, T cells, CD8+ T cells and NK cells in patients may be related to the dysplasia of epithelial cells. Furthermore, the B cells and CD4+ T cells may be related to the malignant growth of the dysplastic epithelial cells.

New insights into the role of the oral leukoplakia microenvironment in malignant transformation.

Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.

Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease

Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.

Correlation of PD-1 and PD-L1 expression in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical study

The programmed cell death protein (PD-1)/programmed cell death protein ligand (PD-L1) pathway and cytotoxic T lymphocyte antigen are the most important co-stimulatory molecules that play a key role in the negative regulation of T cells during carcinogenesis. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in oral leukoplakia and squamous cell carcinoma compared with normal oral mucosa. Twenty-five cases of oral squamous cell carcinoma, oral leukoplakia and normal oral mucosa tissue specimens were immunohistochemically stained to assess PD-1 and PD-L1 expression. The PD-L1 positivity of subepithelial TAFs (p < 0.001) increased with increasing grades of oral leukoplakia. Pearson’s correlation indicated a high positive correlation between the PD-L1 labelling index of epithelial tumour cells and the PD-1 labelling index of tumour infiltrating lymphocytes (p value: 0.005) in OSCC. A high positive correlation was noted between the H-score of PD-L1 positive tumour epithelial cells and the H-score of PD-1 positive tumour infiltrating lymphocytes in OSCC (p value: 0.001). PD-L1 positivity increased in dysplastic epithelial cells from premalignant lesions to malignancy. The sub-epithelial PD-L1 positive TAFs were higher in oral leukoplakia compared to OSCC inferring that PD-L1 positivity in TAFs decreased with malignant transformation. The PD-1 positivity in TILs was higher in oral leukoplakia than in OSCC.

MYC overexpression in inflammatory bowel disease-associated conventional dysplasia and association of subsequent low-grade dysplasia in follow-up biopsies

ObjectiveDiagnosis of inflammatory bowel disease (IBD)-associated dysplastic lesions can be challenging. This study aims to evaluate MYC immunohistochemistry (IHC) as a potential biomarker for IBD-associated dysplasia and compare its effectiveness with p53 IHC. MethodsThe study cohort included resections from 12 IBD patients with carcinoma and concurrent conventional low-grade dysplasia (LGD), as well as biopsies from 21 patients with visible conventional LGD, which were followed up for 2 years with subsequent endoscopic examination. MYC and p53 IHC and MYC-FISH analysis were performed. ResultsSensitivity for LGD detection was 67% (8/12) and 50% (6/12) for MYC and p53, respectively, but the difference was not statistically significant (p = 0.2207). MYC and p53 overexpression were not always mutually exclusive, nor were they always present simultaneously. Patients who presented dysplasia in subsequent biopsies (7/21) were found to be more likely present with multiple LGD polyps and MYC-overexpressed LGD in the initial biopsies, compared to those without subsequent dysplasia (p < 0.05). These dysplastic lesions were commonly associated with chronic colitis (p = 0.0614). The distribution of LGD sites did not show a significant difference between patients with and without subsequent LGD. In MYC overexpressed cases, homogeneously strong nuclear expression was not identified in all dysplastic epithelial cells, and no MYC amplification was found in these cases by FISH. ConclusionMYC IHC can complement p53 IHC as an adjunct biomarker for diagnosing IBD-associated conventional LGD and can be used for the prediction of subsequent LGD in the follow-up biopsies combined with endoscopic features.

Proportion of CD44+ Subset of Tumour Cells in Single Cell Suspension Prepared from FFPET Sections Directly Correlates with Histological Subtyping of Head and Neck Squamous Cell Carcinoma

CD44 expression in tumours imparts potential to progress, metastasize, recurrence, and resistance against antineoplastic therapy. In this study, we sought to describe the variation in the immuno-expression and numeration of MDR1+ and CD44+ potential cancer stem cells in different histological grades and subtypes of head and neck squamous cell carcinoma (HNSCC). Flow-cytometric analysis was performed on single cell suspension prepared from formalin fixed paraffin embedded tissue (FFPET) sections of HNSCC using anti-CD44 and anti-MDR1/ABCB-1 primary monoclonal antibodies. Immunohistochemical (IHC) staining was also carried out using both of these antibodies on HNSCC tissue sections mounted on super frosted glass slides. On immunohistochemical analysis, the mean IRS for CD44 and MDR1 were 8.6364 ±3.02114 and 1.5909 ±1.27674 respectively. When mean immune-expression scores of CD44 antibody and MDR1/ABCB-1 were compared with histological grades and subtypes of HNSCC, the relationship was found to be statistically insignificant. Interestingly, a strong statistical difference (p = 0.000) was observed when the mean score of subset of dysplastic squamous epithelial cells with characteristics of cell stemness (CD326+CD44+) was compared among different histological subtypes of HNSCC using flowcytometric analysis. While no statistically significant association was observed when the mean score for subset of dysplastic cells with potential of drug resistance (CD44+MDR1+) was compared among different histological subtypes of HNSCC. Although potential cancer stem cell marker CD44 and the multidrug resistance maker ABCB-1/MDR1 co-expressed in HNSCC but the proportion of CD326+CD44+ subset of tumour cells (potential cancer stem cells/CSCs) significantly correlates with least aggressive to more aggressive tumour subtypes.

BestCyte® primary screening of 500 ThinPrep Pap Test thin-layers: 3 Cytologists’ Interobserver diagnostic concordance with predicate manual microscopy relative to Truth Reference diagnoses defining NILM, ASCUS+, LSIL+, and ASCH+ thresholds for specificity, sensitivity, and equivalency grading

BackgroundThe BestCyte® Cell Sorter Imaging System (BestCyte) facilitates algorithmic discrimination of clinically relevant cells in Pap test cytopathology by classifying and projecting images of cells in galleries based on cytomorphology. Warranted is awareness of potential BestCyte advantages as measured through 3 cytologists’ interobserver diagnostic concordance, specificity and sensitivity differentials, and equivalency grading relative to manual microscopy (MM). ObjectivesUsing 500 MM-reported ThinPrep thin-layers, analyze: (1) cytologists’ blinded BestCyte screening to raise Bethesda diagnoses; (2) correlate BestCyte and MM diagnoses (i.e., predicate) to establish Truth Reference Diagnoses (TRDx) from concordance between 4 possible diagnoses; (3) analyze cytologists’ and MM predicate diagnoses through 4 diagnostic thresholds defined by TRDx: NILM (Negative) for specificity, and ASCUS+, LSIL+, and ASCH+ (Positive) for graded sensitivity (with abnormal cells decreasing in size with increasing dysplasia); and, (4) statistically determine cytologists’ equivalency grading to MM using 95% Confidence Interval (CI) ranges. Results500 TRDx breakdown (n/%): NILM (241/48.2), ASCUS (79/15.8), ASCH (9/1.80), AGUS (2/0.40), LSIL (86/17.2), HSIL (68/13.6), CA (2/0.40), UNSAT (13/2.60). TRDx breakdown (n/%) per 4 of 4, 3 of 4, 2 of 4 diagnostic concordances: 264 (52.8%), 182 (36.4%), 54 (10.8%), respectively. No cases of discordant diagnoses were recorded. HSIL TRDx were established from 66.2% of 4 of 4 concordances, followed by NILM (59.3%), LSIL (46.5%), ASCUS (41.8%); antithetically, from 4.40% of 2 of 4 concordances. Specificity for MM predicate (NILM): 67.08%; for Cytologists 1, 2, and 3: 89.71%, 82.30%, 97.53%, respectively. For NILM threshold, cytologists revealed Significantly Superior equivalency to MM. Sensitivity for ASCUS+, LSIL+, and ASCH+ thresholds: MM (91.36%, 86.67%, 74.36%); Cytologist 1 (95.88%, 96.97%, 94.87%); Cytologist 2 (95.47%, 95.76%, 93.59%), Cytologist 3 (94.65%, 95.15%, 98.72%), respectively. Cytologists revealed Significantly Superior equivalency to MM for graded Positive thresholds; with Cytologist 3 for ASCUS+ being: Superior. ConclusionsBestCyte detects and efficiently displays abnormal cells in strategic galleries standardizing objectivity by systematizing mosaics of cell-types for cytologists’ consideration. BestCyte fosters consistent, enhanced cytologists’ sensitivity values for the ASCUS+, LSIL+, and ASCH+ Positive thresholds relative to MM. Also, BestCyte facilitates improved specificity and superior equivalency grading to MM reflecting efficient screening, and reduced labor. Confident interpretations of small dysplastic epithelial cells characteristic of HSIL led to exceptional interobserver diagnostic concordance inferring BestCyte is primed for effective cervical cancer screening practice.

Significance Of Tumor Giant Cells In Oral Squamous Cell Carcinoma: A Case Report

Background : Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. OSCC presents with some typical histopathological characteristics like dysplastic epithelial cells with variable degrees of squamous differentiation. These histopathological features make it relatively easy to diagnose conventional squamous cell carcinoma. However, some cases show certain unique features that help in determining the prognosis of the disease. These features include epithelial-mesenchymal interaction, stromal hyalinization, clear cell change, stromal desmoplasia, perineural invasion, vascular invasion, tissue eosinophilia, giant cells and tertiary lymphoid follicle formation. The presence of giant cells in OSCC can be the result of foreign body reaction to keratin or due to formation of malignant tumor giant cells in poorly differentiated carcinomas. The giant cells showing pleomorphic features can be helpful in predicting the prognosis of the disease.

Human Intestinal Spirochetosis Incompatible With Dysplastic Adenomatous Epithelium

Human intestinal spirochetosis (HIS) refers to the colonization of spirochetal bacteria in the human intestinal tract. HIS caused by Brachyspira spp. has been recognized for decades, but their pathological and clinical significance is largely unclear. The coincidence of dysplasia in adenoma or adenocarcinoma and HIS is very rare, and whether spirochetes can colonize on dysplastic epithelium remains controversial. Here, we report a case that showed abrupt abolition of mucosal surface fringe formation on a tubular adenoma (TA) and increased cytoplasmic MUC1 expression in the dysplastic epithelial cells compared with adjacent nondysplastic colonocytes. The findings support the hypothesis that the epithelial colonization of spirochetes is significantly reduced by dysplasia likely due to loss of microvilli, and an increase of epithelial MUC1 expression might contribute to reduced spirochetal colonization in colonic mucosa.

Lactobacillus reuteri-an old acquaintance takes on a new task in colorectal tumor surveillance.

In this issue of Cancer Cell, Bell etal. identify the commensal bacterium Lactobacillus reuteri and its major metabolite reuterin as an important gatekeeper and promising target in colorectal cancerogenesis. They decipher a metabolic interplay in which L.reuteri is suppressed by metabolites from dysplastic intestinal epithelial cells which in turn are highly sensitive to the oxidative effects of the electrophile reuterin.

Cytomorphological analysis of urinary cells among active and passive cigarette smokers in South-West, Nigeria

Introduction: Cigarette smoke contains thousands of identified chemicals, among which sixty-nine (69) of these chemicals are known to be poisonous to humans and are capable of causing cancer in any part of the body. This study was conducted to evaluate the cytology of urinary cells among active and passive cigarette smokers in South-Western Nigeria. Materials and Methods: Urine samples were collected from 250 active cigarette smokers and 200 passive cigarette smokers who live in South-Western, Nigeria. The urine specimen was collected from participants and processed using the standard technique for microscopic examination. Smears were stained with haematoxylin and eosin and Papanicolaou stain. Results: The urinary smears of passive cigarette smokers revealed normal superficial squamous cells, transitional cells, cast, necrotic debris and mild inflammatory cells, while that of active cigarette smokers revealed high cellular turnover, protein casts, dysplastic epithelial cells and atypical urothelial cells with degenerative features. Conclusion: On the basis of this study, the cytomorphological analysis of urinary smears among active cigarette smokers revealed cytopathological features which connote the harmful effects of the chemical constituents present in cigarette smoke.

Epigenetic Reprogramming in Oral Epithelial Dysplasia using Sodium Valproate: an in vitro study parallel to the SAVER trial

Background Current management of oral epithelial dysplasia (OED) focuses on preventing malignant transformation of the index lesion without addressing the risk of cancer development at other oral sites. Sodium valproate (SV) was identified as a potential chemopreventive agent for head and neck cancer owing to the dose- and time-dependent protective effect seen in a large retrospective cohort study. Objective Determine the effect of SV on cell proliferation, histone deacetylase (HDAC) activity, and protein expression in dysplasia cell lines in monolayer and develop 3D organotypic models to assess the effect of SV on invasion. Methods • Dysplasia cell lines (D20, DOK, and D35), normal oral keratinocytes (FNB6), and oral cancer fibroblasts (LIV9 and LIV22) cultured in monolayer. • MTT assays, HDAC-glo assay, Western blotting, and LINE-1 pyrosequencing. • 3D collagen models (cancer fibroblasts and dysplastic epithelial cells) exposed to 1 mM SV for 7 days before processing. Changes in invasion pattern and depth are assessed on hematoxylin and eosin–stained slides. Results Exposure to 1 mM SV for 48 hours reduces cell proliferation and HDAC activity and results in increased expression of acetylated histones vs control. SV has no effect on global DNA methylation. 3D models have been developed and are being optimized for gene expression studies. Conclusions This in vitro study runs parallel to the SAVER trial, a multicenter double-blind randomized controlled trial of SV vs placebo in 110 patients with high-risk OED. We have confirmed the mechanism of action of SV as an HDAC inhibitor with higher expression of acetylated histones when dysplasia cell lines are exposed to SV at clinically relevant concentrations.

Promising targets of chrysin and daidzein in colorectal cancer: Amphiregulin, CXCL1, and MMP-9

Colorectal cancer is one of the primary causes of cancer-related mortality worldwide. The tumor microenvironment contains growth factors; inflammatory chemokines, matrix metalloproteinases, and pro-oxidants leading to cancer development and progression. Phytochemicals have been used as the main source of anti-cancer agents. Accordingly, the effect of two natural flavonoids (Chrysin and Daidzein) was investigated on the level of amphiregulin (AREG), chemokine ligand (CXCL1), and matrix metalloproteinase-9 (MMP-9) in 1, 2-dimethylhydrazine dihydrochloride (DMH) induced colorectal cancer. Rats were injected by DMH (40 mg/kg/week S.C.) for 16 weeks concomitantly with 2% dextran sodium sulfate (DSS) in drinking water for three cycles. Rats were orally treated with chrysin (125 and 250 mg/kg) and daidzein (5 and10 mg/kg) three times/week for the last 8 weeks. DMH + DSS group showed a significant (P < 0.05) increase in the levels of AREG (2386 ± 18 vs 1377 ± 10 pg/ml), CXCL1 (18 ± 0.9 vs 6 ± 0.83 <mu>g/ml), MMP-9 (1355 ± 88 vs 452 ± 7 pg/ml) compared to normal rats. These findings were associated with a potent antioxidant activity against cytochrome P450 2E1; (CYP2E1). Histopathological findings of the DMH + DSS group showed focal hyperplasia of the mucosa lining overlying crypts with moderate inflammation, dysplastic epithelial cells, and loss of goblet cells. Chrysin and daidzein treatment significantly (P < 0.05) restored the biochemical alterations and reverted histopathological findings near to the normal status. Moreover, chrysin and daidzein exerted anticancer activity against SW620 cells that were associated with decreased the protein expression of p-ERK/ERK and p-AKT/AKT. In conclusion, this study highlighted the potential anticancer role of chrysin and daidzein in the treatment of colon cancer.

Intraocular Invasion of Ocular Surface Squamous Neoplasia Through a Corneal Wound.

PurposeWe report a case of intraocular invasion of ocular surface squamous neoplasia (OSSN) through a cataract surgery wound that manifested as an anterior chamber membrane, and perform a review of the literature.MethodsAn 87-year-old woman with history of an incompletely excised OSSN 10 days prior presented with decreased vision due to an anterior chamber membranous film that seemed connected to an old cataract wound. The membrane was biopsied, and histopathology revealed dysplastic squamous epithelial cells of conjunctival origin. Ten days later the tumor expanded to cover the entire iris surface, and a modified enucleation was performed.ResultsHistopathology revealed invasive OSSN extending deep to the ciliary body and laterally into the anterior chamber. The patient developed a submandibular node metastasis 7 months later. Literature review revealed six cases of invasive OSSN resulting from extension through a corneal wound, with varied presentations and outcomes.ConclusionOur case is the first to report invasive OSSN presenting as an anterior chamber membrane as a result of incomplete excision of an ocular surface malignancy adjacent to a corneal wound poses a risk for intraocular tumor extension and distant metastasis.Electronic supplementary materialThe online version of this article (10.1007/s40123-020-00294-2) contains supplementary material, which is available to authorized users.

Correlation of Dysplastic Changes of Squamous Epithelial Cells to Bacterial Vaginosis Based on Nugent Score in the Cervical Smears of Patients with Vaginal Discharge

Background: Worldwide Cervical cancer is responsible for more than half a million new cases and a quarter of a million deaths annually. Many Researches has established the causal role of oncogenic human Papillomavirus (HPV) infection in the pathogenesis of invasive cervical cancer and its precursor lesions. Bacterial vaginosis(BV) is one of the most common conditions of childbearing aged women worldwide, and considering a possible synergy of an imbalanced vaginal environment with cervical preneoplasia,it is clear that greater attention needs to be given to this condition. Objective: To find out an association between Nugent score and dysplastic epithelial cell changes in the cervical smears of patients with vaginal discharge.Subjects and Methods:This is a descriptive study conducted on 100 cervical smears from women of reproductive group with vaginal discharge.Paponicolaou stained and Gram stained smears were studied. The proportion of cervical smears with normal flora and dysplastic changes as well as that of smears with Bacterial vaginosis and dysplastic changes were calculated and compared.Results:19 smears were scored as BV,.2 out of 19 smears (10.5%)were showing epithelial cell abnormality.1 out of 38 (2.6%)smears having normal vaginal flora was reported as ASC and 6 out of 43(14%) smears in the intermediate category were reported as ASC(5) and HSIL(1). Statistical analysis was done by Chi-square test using IBM-SPSS Statistics-22 statistical package.The correlation between Bacterial vaginosis and dysplastic changes were not found to be statistically significant.Conclusion: There is no definite correlation of Bacterial vaginosis with dysplastic changes in the cervical smear of patients with vaginal discharge related with the risk for cervical carcinogenesis. Evaluation of larger cohort of subjects over a prolonged time frame is required to assess the influence of Bacterial vaginosis in cervical carcinogenesis.

OCULAR SURFACE SQUAMOUS CELL NEOPLASIA IN A 25 YEARS MAN FROM D.I.KHAN, PAKISTAN

Ocular surface squamous neoplasia (OSSN) is a term that describes the spectrum of abnormal growth of atypical squamous epithelial cells of the conjunctiva, cornea, and sclera. It is more common in people working for long in sun-exposed areas. It resembles other common ocular surface conditions such as pterygium, pinguecula, atopic conjunctivitis, diffuse episcleritis, chronic blepharoconjunctivitis which may result in the wrong diagnosis of the entity. Here we report a case of OSSN in a 25 years old man which was referred to us as a case of pterygium. An excisional biopsy revealed clusters of dysplastic squamous epithelial cells.

UrokinaseType Plasminogen Activator Receptor Expression In Colorectal Neoplasms

Background—The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. Aims—To study the involvement of uPAR in colorectal carcinogenesis. Methods— fourty four cases of colorectal adenocarcinoma were obtained and diagnosed as colonic carcinoma with it's grade received as formalin-fixed, paraffin-embedded tissue in AL-Nasiriyah teaching hospital with cases of carcinoma also 6 cases of normal endoscopic biopsies used as control –ve and 10 cases of adenoma with dysplastic changes all these cases stain by immunohistochemical methods for expression and localisation of uPAR. Results_ all the cases of endoscopic biopsies were –ve for these receptors so used as –ve control, while cases of adenoma 3 out of 10 cases showing focal positivity in areas of dysplasia, while the cases of invasive carcinoma showing diffused positivity and the case percent of positivity depend on grade so high grade tumor showing a high percentage of positivity. Conclusions—Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.

Fallopian tube initiation of high grade serous ovarian cancer and ovarian metastasis: Mechanisms and therapeutic implications

Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Although outcomes have improved in recent years, there remains an unmet clinical need to understand the early pathogenesis of ovarian cancer in order to identify new diagnostic approaches and agents of chemoprevention and chemotherapy. While high grade serous ovarian cancer (HGSOC), the most abundant histotype, was initially thought to arise from the ovarian surface epithelium, there is an increasing body of evidence suggesting that HGSOC originates in the fallopian tube. With this new understanding of cell of origin, understanding of disease development requires analysis with a novel perspective. Currently, factors that drive the initiation and migration of dysplastic tubal epithelial cells from the fallopian tube to the ovary are not yet fully defined. These factors include common mutations to fallopian tube epithelial cells, as well as factors originating from both the fallopian tube and ovary which are capable of inducing transformation and dissemination in said cells. Here, we review these changes, their causative agents, and various potential means of intervention.

Epidemiology of invasive ocular surface squamous neoplasia in Canada during 1992–2010

BackgroundOcular surface squamous neoplasia (OSSN) is the most common non-pigmented ocular surface malignancy. It is classified as invasive OSNN (IOSSN) when the underlying stroma are infiltrated by dysplastic squamous epithelial...