Whole Exome Profiling of Ocular Surface Squamous Neoplasia.
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ABSTRACT:
SUBMITTER: Galor A
PROVIDER: S-EPMC4695283 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Publications
Whole Exome Profiling of Ocular Surface Squamous Neoplasia.
Galor Anat A Karp Carol L CL Sant David D Joag Madhura M Shalabi Nabeel N Gustafson Christopher B CB Wang Gaofeng G
Ophthalmology 20150811 1
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Project description:PurposeTo determine genetic mutational profiles in patients with Ocular Surface Squamous Neoplasia (OSSN) using whole exome sequencing.MethodsProspective, case-series study. Patient recruitment was conducted in a single tertiary referral center from April to September 2017. Specimens were obtained by incisional biopsies of tumors from ten eyes with histopathologic confirmation of OSSN. DNA whole exome sequencing and mutation analysis were performed.ResultsTen patients with clinically-diagnosed OSSN underwent DNA whole exome sequencing analysis. Deleterious mutations in 305 genes known to drive tumor development and progression were found. These mutations centered around two main pathways: DNA repair/cell cycle and development/growth. All ten samples had at least one mutation in a DNA repair/cell cycle gene and all but one sample had one in a development/growth gene. The most common mutation was found in TP53 and HGF (both present in 50% of cases) and mutually exclusive mutations were found in BRCA1 and BRCA2 (50% of cases). Mutations in APC, MSH6, PDGFRA, and PTCH1 were found in 40% of cases. Global mutation analysis identified ultraviolet induced radiation as the only mutational signature present in the dataset.ConclusionsMutations found in samples from patients with OSSN are mainly induced by ultraviolet radiation and occur within two main pathways related to DNA repair/cell cycle and development/growth. There are many clinically available drugs and several others being evaluated in clinical trials that target the genes found mutated in this study, offering new therapeutic options for OSSN.
| S-EPMC7686168 | biostudies-literature
Project description:ImportanceThere is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression.ObjectiveTo describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability.Design, setting, and participantsProspective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features.ExposuresComprehensive history, slitlamp examination, and photography before excision biopsy.Main outcomes and measuresFrequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using χ2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the κ statistic. Examiners' assessments were compared with a reference.ResultsAmong 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P = .002) and tended to have lower levels of education than patients with benign lesions (P = .001). Females predominated (67% of OSSN vs 64% of benign lesions; P = .65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P < .001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P < .001), severe inflammation (6.7% vs 0.3%; P < .001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P < .001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (κ, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%.Conclusions and relevanceWith overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help.
| S-EPMC5321496 | biostudies-literature
Project description:ATP-binding cassette subfamily B member 5 (ABCB5) is a new member of the ATP-binding cassette superfamily and has been reported as a novel marker for limbal stem cell (LSC), which is essential for corneal homeostasis. ABCB5 expression has also been discovered in the subpopulation of several cancer cells containing the cancer stem cell (CSC). However, the pathogenetic relationship between LSC and CSC and ABCB5 in the ocular surface squamous neoplasm (OSSN) is still entirely unknown. To improve understanding of the role of ABCB5 in OSSN, we performed immunohistochemistry for ABCB5 in nine OSSN case series. While expression of ABCB5 is restricted to the basal epithelial cell layer in the normal limbus, elevated expressions of ABCB5 were clearly observed in all OSSN, and there was some breadth in the range of intensity of ABCB5 expression. Interestingly, the elevated expression patterns of ABCB5 in OSSN could be classified in three categories: perivascular, marginal and diffuse patterns. Our findings demonstrated for the first time that the expression of ABCB5 was upregulated in OSSN and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN.
| S-EPMC4740799 | biostudies-other
Project description:Purpose:The clinical diagnosis of ocular surface squamous neoplasia is challenging, mostly requiring excisional biopsy. Human tumor angiogenesis is characterized by abnormal vessel architecture and transvascular hyperpermeability. This case report describes features of fluorescein and indocyanine green angiography in a case of conjunctival intraepithelial neoplasia. Observations:Color photography, optical coherence tomography, fluorescein and indocyanine green angiography were performed in a patient with suspected conjunctival intraepithelial neoplasia before excisional biopsy and histologic confirmation of clinical diagnosis. Fluorescein dye showed extensive early extravascular dye leakage within the limits of the lesion. Indocyanine green dye displayed corneal terminal vessel bulbs with early leakage after 70 seconds and showed diffuse intralesional dye leakage after 7 minutes. Conclusions:Increased fluorescein and early indocyanine green dye leakage can be used to confirm active angiogenesis already in early stages of dysplastic ocular surface squamous neoplasia. Late leakage of indocyanine green dye may be due to chronic transvascular hyperpermeability within intrinsic tumor vessels. The leakage behaviour of intravenous dyes has the potential to serve as a diagnostic indicator of active growth in dysplastic ocular surface neoplastic lesions.
| S-EPMC7495007 | biostudies-literature
Project description: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.
| S-EPMC7708601 | biostudies-literature
Project description:Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.
| S-EPMC9392743 | biostudies-literature
Project description:BackgroundOcular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined.ResultsTissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples.ConclusionWe identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN.
| S-EPMC2859758 | biostudies-literature
Project description:ObjectiveTo determine modifiable risk factors of ocular surface squamous neoplasia (OSSN) in Kenya using disease-free controls.MethodsAdults with conjunctival lesions were recruited at four eye care centres in Kenya and underwent excision biopsy. An equal number of controls having surgery for conditions not affecting the conjunctiva and unrelated to ultraviolet light were group-matched to cases by age group, sex and eye care centre. Associations of risk factors with OSSN were evaluated using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Continuous variables were compared using the t-test or the Wilcoxon-Mann-Whitney U-test depending on their distribution.ResultsA total of 131 cases and 131 controls were recruited. About two-thirds of participants were female, and the mean age of cases and controls was 42.1 years and 43.3 years, respectively. Risk factors for OSSN were HIV infection without antiretroviral therapy (ART) use (OR = 48.42; 95% CI: 7.73-303.31) and with ART use (OR = 19.16; 95% CI: 6.60-55.57), longer duration of exposure to the sun in the main occupation (6.9 h/day vs. 4.6 h/day, OR = 1.24; 95% CI: 1.10-1.40) and a history of allergic conjunctivitis (OR = 74.61; 95% CI: 8.08-688.91). Wearing hats was protective (OR = 0.22; 95% CI: 0.07-0.63).ConclusionMeasures to prevent and control HIV, reduce sun exposure such as wearing hats and control allergic conjunctivitis are recommended.
| S-EPMC5574019 | biostudies-literature
Project description:There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0-100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals.
| S-EPMC3272209 | biostudies-other
Project description:The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
| S-EPMC3977825 | biostudies-literature