Biomarkers of epithelial-mesenchymal transition: E-cadherin and beta-catenin in malignant transformation of oral lesions.

Objective: Detecting oral lesions at high risk of becoming cancer may enable early interventions to prevent oral cancer. The diagnosis of dysplasia in an oral lesion is used to predict this risk but is subject to interobserver and intraobserver variability. Studying biomarkers or molecular markers that reflect underlying molecular alterations can serve as an additional and objective method of risk assessment. E-cadherin and beta-catenin, molecular markers of epithelial-mesenchymal transition (EMT), potentially contribute to early malignant progression in oral tissue. This narrative review provides an overview of EMT, its relation to oral cancer, and the interaction among E-cadherin, beta-catenin, and the Wnt pathway in malignant progression of oral tissue. Methods: Full-text literature on EMT, E-cadherin, beta-catenin, oral epithelial dysplasia, and oral cancer was retrieved from PubMed and Google Scholar. Results: Sixty original research articles, reviews, and consensus statements were selected for review. Discussion: EMT, a biological mechanism characterized by epithelial and mesenchymal changes, can contribute to cancer development. Molecular markers of EMT including TWIST, vimentin, and N-cadherin may serve as prognostic markers of oral cancer. Dependent on Wnt pathway activity and the loss of membranous E-cadherin, E-cadherin and beta-catenin can play various roles along the spectrum of malignant progression, including tumour inhibition, early tumour progression, and late-stage tumour progression. Cross-sectional immunohistochemical research has found changes in expression patterns of E-cadherin and beta-catenin from normal oral tissue, oral epithelial dysplasia, to oral squamous cell carcinoma. Conclusion: Future research should explore the longitudinal role of EMT markers in predicting malignant progression in oral tissue.

Objectif: La détection de lésions buccales présentant un risque élevé d'évoluer en cancer peut permettre des interventions précoces pour prévenir le cancer de la bouche. Le diagnostic de dysplasie dans le cas de lésions buccales sert à prédire ce risque, mais il est soumis à une variabilité d'un observateur à l'autre et avec le même observateur. L'étude de marqueurs biologiques ou de marqueurs moléculaires correspondant à des altérations moléculaires sous-jacentes peut constituer une méthode objective supplémentaire d'évaluation des risques. L'E-cadhérine et la bêta-caténine, des marqueurs moléculaires de la transition épithélio-mésenchymateuse (TEM), pourraient contribuer aux premières étapes de l'évolution maligne du tissu buccal. Cette revue narrative donne un aperçu de la TEM, de ses liens avec le cancer de la bouche et de l'interaction entre l'E-cadhérine, la bêta-caténine et la voie de signalisation Wnt dans l'évolution maligne du tissu buccal. Méthodes: On a obtenu le texte intégral d'études portant sur la TEM, l'E-cadhérine, la bêta-caténine, la dysplasie épithéliale buccale et le cancer de la bouche sur PubMed et Google Scholar. Résultats: Soixante articles sur des études originales, des revues et des déclarations de consensus ont été sélectionnés aux fins d'examen. Discussion: La TEM, un mécanisme biologique caractérisé par des changements épithéliaux et mésenchymateux, peut contribuer à l'apparition d'un cancer. Les marqueurs moléculaires de la TEM, notamment TWIST, la vimentine et la N-cadhérine, peuvent servir de marqueurs pronostiques du cancer de la bouche. En fonction de l'activité de la voie de signalisation Wnt et de la perte de l'E-cadhérine membraneuse, l'E-cadhérine et la bêta-caténine peuvent jouer divers rôles dans le spectre de l'évolution maligne, notamment l'inhibition tumorale, la progression tumorale précoce et l'évolution tumorale avancée. Des études transversales d'immunohistochimie ont révélé des changements dans les modèles d'expression de l'E-cadhérine et de la bêta-caténine avec le passage du tissu buccal normal, de la dysplasie épithéliale buccale au carcinome squameux de la bouche. Conclusion: À l'avenir, des études devraient explorer le rôle longitudinal des marqueurs de la TEM dans la prévision de l'évolution maligne dans les tissus buccaux.

Controversies regarding oral lichen planus and lichenoid-dysplastic lesions.

Objective: Oral lichen planus (OLP) is an immune-mediated condition featuring chronic inflammation. The World Health Organization classifies OLP as potentially malignant, but it is believed that the malignant transformation of OLP occurs in lesions with both lichenoid and dysplastic features (LD). This review discusses the issues surrounding OLP and LD, including their malignancy, classification, and categorization, and whether lichenoid inflammation causes dysplastic changes in LD or vice versa. Methods: English full-text literature on OLP, LD and/or dysplasia was retrieved from PubMed, CINAHL, and Google Scholar. Results: Thirty-six publications including original research articles, reviews, meta-analyses, books, reports, letters, and editorials were selected for review. Discussion: Research suggests that OLP has malignant potential, although small, and that LD should not be disregarded, as dysplasia presenting with or without lichenoid features may develop into cancer. There is also disagreement over the classification and categorization of LD. Different terms have been used to classify these lesions, including lichenoid dysplasia, OLP with dysplasia, and dysplasia with lichenoid features. Moreover, in LD, it is not clear if dysplasia or lichenoid infiltration appears first, and if inflammation is a response to dysplasia or if dysplasia is a response to the persistent inflammation. The main limitation in the literature is the inconsistency and subjective nature of histological diagnoses, which can lead to interobserver and intraobserver variation, ultimately resulting in the inaccurate diagnosis of OLP and LD. Conclusion: Although further research is required to understand OLP and LD, both lesions should be considered potentially malignant and should not be disregarded.

Objectif: Le lichen plan buccal (LPB) est une pathologie auto-immune qui se présente sous la forme d'une inflammation chronique. Selon la classification de l'Organisation mondiale de la santé, le LPB est une pathologie potentiellement maligne. Toutefois, on soupçonne que la transformation maligne du LPB se produit dans des lésions présentant à la fois des caractéristiques lichénoïdes et dysplasiques (LD). Cet examen porte sur les questions relatives au LPB et aux LD, notamment leur malignité, leur classification et leur catégorisation, et pour savoir si l'inflammation du lichénoïde entraîne des changements dysplasiques des LD ou vice versa. Méthodes: On a utilisé le texte intégral de documents rédigés en anglais sur le LPB, les LD et la dysplasie issus de PubMed, de CINAHL et de Google Scholar. Résultats: Trente-six publications, notamment des articles sur des études originales, des revues, des méta-analyses, des livres, des rapports, des lettres et des éditoriaux, ont été sélectionnées aux fins d'examen. Discussion: Des études suggèrent que le LPB est potentiellement malin, bien que ce potentiel soit faible, et que les LD ne doivent pas être ignorés : en effet, une dysplasie peut évoluer en cancer, qu'elle présente des caractéristiques lichénoïdes ou non. On constate également un désaccord quant à la classification et à la catégorisation des LD. Différents termes ont été utilisés pour la classification de ces lésions, notamment « dysplasie lichénoïde ¼, « LPB dysplasique ¼ et « dysplasie à caractéristiques lichénoïdes ¼. De plus, dans le cas des LD, on ne sait pas avec certitude si la dysplasie ou l'infiltration lichénoïde apparaît en premier, ni si l'inflammation découle de la dysplasie ou si la dysplasie est une conséquence de l'inflammation persistante. La principale limite de la littérature est due aux incohérences et à la nature subjective des diagnostics histologiques, qui peut entraîner des variations d'un observateur à l'autre ou même avec un même observateur, ce qui entraîne à terme des diagnostics erronés de LPB et de LD. Conclusion: Bien que d'autres études soient nécessaires pour comprendre le LPB et les LD, les lésions de ces 2 catégories doivent être considérées comme potentiellement malignes et ne doivent pas être ignorées.

Helicobacter pylori East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report.

BACKGROUND: Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes. CASE PRESENTATION: We report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations. CONCLUSION: Ovarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.

Growing teratoma syndrome in children and adolescents: Prevalence and surgical outcome.

INTRODUCTION: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome. PATIENTS AND METHODS: The clinical notes of patients diagnosed with stage III and IV malignant germ cell tumors from January 2010 until December 2020 at our Institution were retrospectively reviewed. The prevalence of GTS, treatment strategies, survival, and outcome were analyzed. RESULTS: Thirty-three patients with high-stage malignant germ cell tumors were diagnosed in our institution in the analyzed period. Nine patients (28%) had radiologic evidence of enlargement of persistent masses with normal markers after chemotherapy; these patients were classified as GTS patients. All nine patients underwent resection of metastatic lymph nodes, and six had surgery on visceral metastases. In six patients, radical excision of all metastatic sites was achieved; five patients are alive and in complete remission, while one died because of peri-operative complications. Out of the three patients who could not achieve radical excision of the metastases, two died of progressive disease, and one is alive with progressive disease. CONCLUSIONS: Patients affected by GTS have a risk of progression of chemotherapy-resistant disease and death. Radical surgical excision is essential to achieve disease control and long-term survival.

Genetic Profiling of Sebaceous Carcinoma Arising from an Ovarian Mature Teratoma: A Case Report.

Ovarian mature teratomas (OMTs) originate from post-meiotic germ cells. Malignant transformation occurs in approximately 1-2% of OMTs; however, sebaceous carcinoma arising from OMTs is rare. This is the first report of a detailed genomic analysis of sebaceous carcinoma arising from an OMT. A 36-year-old woman underwent evaluation for abdominal tumors and subsequent hysterectomy and salpingo-oophorectomy. Pathologically, a diagnosis of stage IA sebaceous carcinoma arising from an OMT was established. Eight months post-surgery, the patient was alive without recurrence. Immunohistochemically, the tumor was negative for mismatch repair proteins. A nonsense mutation in TP53 (p.R306*) and a deletion in PIK3R1 were identified. Single nucleotide polymorphisms across all chromosomes displayed a high degree of homozygosity, suggestive of uniparental disomy. Herein, the OMT resulting from the endoreduplication of oocytes underwent a malignant transformation to sebaceous carcinoma via TP53 as an early event and PIK3R1 as a late event.

Endometrioid adenocarcinoma arising from abdominal wall endometriosis: A case report and literature review.

Endometriosis, affecting 6%-10% of women of reproductive age, can lead to severe symptoms such as chronic pelvic pain and infertility. Among its rarer manifestations is abdominal wall endometriosis (AWE), which has been increasingly reported following cesarean deliveries. This case discusses a 39-year-old woman who presented with a 13-year history of cyclical pain at her cesarean section scar, exacerbated over the last year by the development of a painful abdominal mass. Medical evaluations indicated endometriosis at the scar, with further investigations including ultrasound and magnetic resonance imaging showing involvement of the rectus abdominis muscle. Elevated tumor markers HE4 and CA-125, along with a biopsy, confirmed adenocarcinoma. The patient underwent extensive surgical treatment, including the resection of the mass, hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. Pathology confirmed moderately differentiated infiltrative adenocarcinoma originating from endometriosis. Despite the absence of postoperative chemotherapy, the patient showed no recurrence, emphasizing the effectiveness of comprehensive surgical management. This case highlights the critical importance of recognizing the potential for malignant transformation in AWE, particularly following cesarean deliveries, and underscores the necessity for vigilant monitoring and personalized treatment strategies. The management of AWE, especially when malignant transformation is suspected, necessitates a multidisciplinary approach similar to that used in ovarian cancer, focusing on rigorous surgical intervention and the potential for adjuvant therapies.

The Transformation of Neck Unicentric Castleman's Disease to Follicular Dendritic Cell Sarcoma.

A patient with a large neck mass underwent appropriate imaging, routine blood tests, and serological evaluations. The medical history revealed the patient had undergone a lymphadenectomy in the same region 8 years ago, and the pathological diagnosis was the hyaline-vascular subtype of unicentric Castleman's disease (UCD). The incisional biopsy and subsequent histopathological and immunohistochemical examination revealed the diagnosis of follicular dendritic cell sarcoma, consistent with the malignant transformation of UCD. UCD is uncommon and the malignant transformation of UCD is extremely rare in the head and neck region. Regional lymph node resection of one or more adjacent regions is the preferred treatment choice. Appropriate treatment procedures for UCD and regular follow-up are essential for a good prognosis. Laryngoscope, 2024.

[Malignant transformation of Ollier disease-related multiple glioma with IDH1 p.R132C mutation].

A 21-year-old man who was diagnosed with Ollier disease at the age of 1 year developed incidental multiple gliomas at the age of 15 years. Subsequently, the multiple gliomas enlarged and the patient underwent three surgical removals. Genetic analysis revealed the IDH1 p.R132C mutation in the gliomas, and histopathology showed malignant transformation. Despite multimodality treatment, the gliomas could not be controlled, and the patient died at the age of 23 years. Ollier disease is a rare disease with IDH1/2 mutations and is often associated with gliomas. However, there are very few reports on genetic analysis of IDH1/2 mutations and long-term follow-up in Ollier disease-related gliomas. Genetic analysis of IDH mutations may contribute to the elucidation of its pathogenesis. The cross-departmental collaboration is required for long-term follow-up of Ollier disease-related gliomas.

Whole-exome sequencing-based mutational profiling of hepatocellular adenoma malignant transformation to hepatocellular carcinoma.

Hepatocellular adenoma (HCA) represents a rare benign hepatic neoplasm with potential for malignant transformation into hepatocellular carcinoma (HCC), yet the underlying mechanism remains elusive. In this study, we investigated the genomic landscape of this process to identify therapeutic strategies for blocking malignant transformation. Using micro-detection techniques, we obtained specimens of adenoma, cancerous neoplasm and adjacent normal liver from three patients undergoing hepatic resection surgery. Whole-exome sequencing (WES) was performed, and genomic interactions between HCA and HCC components within the same tumour were evaluated using somatic variant calling, copy number variation (CNV) analysis, clonality evaluation and mutational signature analysis. Our results revealed genomic heterogeneity among patient cases, yet within each sample, HCA and HCC tissues exhibited a similar mutational landscape, suggesting a high degree of homology. Using nonnegative matrix factorization and phylogenetic trees, we identified shared and distinct mutational characteristics and uncovering necessary pathways associated with HCA-HCC malignant transformation. Remarkably, we found that HCA and HCC shared a common monoclonal origin while displaying significant genetic diversity within HCA-HCC tumours, indicating fundamental genetic connections or evolutionary pathways between the two. Moreover, elevated immune therapy-related markers in these patients suggested heightened sensitivity to immune therapy, providing novel avenues for the treatment of hepatic malignancies. This study sheds light on the genetic mechanisms underlying HCA-HCC progression, offering potential targets for therapeutic intervention and highlighting the promise of immune-based therapies in managing hepatic malignancies.

Diaphragmatic clear cell carcinoma with Lynch syndrome after surgery for atypical endometrial hyperplasia and ovarian endometriosis: A case report.

Clear cell carcinoma (CCC) of the diaphragm is rare, with an origin that is reported to be associated with malignant transformation of extraperitoneal endometriosis. Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome caused by germline pathogenic variants in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. Women with LS have a significantly increased lifetime risk of endometrial and ovarian cancer. CCC is a common histology of endometriosis- and LS-associated malignancy. The present study describes the case of a 51-year-old woman with an intra-abdominal mass found during a routine physical examination. The patient had undergone total hysterectomy and bilateral adnexectomy for atypical endometrial hyperplasia (AEH) and ovarian endometriosis, respectively, 3 years previously. Enhanced computed tomography showed a mass on the surface of the liver. Laparoscopic examination of the abdominal cavity revealed a tumor on the underside of the right diaphragm, which was then surgically excised. Pathological examination of the excised tumor, along with immunohistochemistry, led to a diagnosis of CCC. Since LS was suspected due to the genetic family history of the patient, microsatellite instability analysis was performed on the diaphragmatic tumor, and the results were positive. Immunohistochemistry was performed for MMR proteins in AEH and CCC cells, both of which revealed loss of MSH2 and MSH6 expression. Following detailed genetic counseling, genetic testing of MMR genes was performed, revealing a germline pathogenic variant in MSH2 (c.1000C>T, p.Gln344*), thus confirming the diagnosis of LS. To the best of our knowledge, this is the first case report of concurrent diaphragmatic CCC and LS. Patients with LS and endometriosis are at risk of developing ovarian cancer or intra-abdominal malignant tumors. In addition, immunohistochemistry screening for MMR proteins should be considered in patients with AEH and a family history of LS-related cancer, to enable early clinical intervention in cases of endometrial cancer.

Role of Stem Cells in the Pathogenesis and Malignant Transformation of Oral Submucous Fibrosis.

BACKGROUND: Pathogenesis and malignant potential of Oral submucous fibrosis(OSMF) have always been a topic of interest among the researchers. Despite OSMF being a collagen metabolic disorder, the alterations occurring in the connective tissue stroma affects the atrophic surface epithelium in later stages and progresses to malignant phenotypes. The present review aims to summarize the role of stem cells in the pathogenesis and malignant transformation of oral submucous fibrosis. MATERIALS AND METHODS: A literature search was carried out using data banks like Medline and Embase, google scholar and manual method with no time frame, pertinent to the role of mucosal stem cells in OSMF and its malignisation. The relevant literature was reviewed, critically appraised by all the authors and compiled in this narrative review. RESULTS: Critical appraisal and evaluation of the data extracted from the selected articles were compiled in this review. The collated results highlighted the upregulation and downregulation of various stem cell markers during the progression and malignisation of OSMF were depicted in a descriptive and detail manner in the present review. CONCLUSION: We highlight the potential of mucosal stem cells in the regulation and malignisation of OSMF. However, future large-scale clinical studies will be needed to support whether manipulation of this stem cells at molecular level will be sufficient for the treatment and preventing the malignant transformation of OSMF.

MRI features of ovarian teratomas with somatic-type malignancy and mature cystic teratomas.

PURPOSE: We evaluated the magnetic resonance imaging (MRI) features of ovarian teratomas with somatic-type malignancy (TSMs) and benign ovarian mature cystic teratomas (MCTs) to determine the diagnostic contribution of the MRI findings for differentiating these two teratomas. METHODS: We compared the MRI findings between ovarian TSMs (n = 10) and MCTs (n = 193), and we conducted a receiver operating characteristic (ROC) analysis to determine the MRI findings' contribution to the differentiation of TSMs from MCTs. RESULTS: The maximum diameters of whole lesion and the largest solid component in the TSMs were larger than those of the MCTs (p = 0.0001 and p < 0.0001, respectively). Fat tissue in solid components was seen in 73/116 (62.9%) MCTs but in none of the TSMs (p = 0.0001). Ring-like enhancement in solid components was seen in 60/116 (51.7%) MCTs and none of the TSMs (p = 0.0031). On dynamic contrast-enhanced MRI (DCE MRI), all of the solid components in the TSMs showed a high- or intermediate-risk time intensity curve (TIC), and those in 113 of the 116 (97.4%) MCTs showed a low-risk TIC (p < 0.0001). The area under the curve of the ROC analysis using the high-/intermediate-risk TIC on DCE MRI was the highest (0.99) for differentiating TSMs from MCTs: sensitivity 100%, specificity 97.4%, positive predictive value 75.0%, negative predictive value 100%, and accuracy, 97.6%. CONCLUSION: Compared to ovarian MCTs, ovarian TSMs are larger and have larger solid components with high- or intermediate-risk TICs on DCE MRI. Ovarian MCTs frequently show small solid components with fat tissue, ring-like enhancement, and a low-risk TIC on DCE MRI.

Occult clear cell carcinoma arising from oxidative stress­exposed cystic adenomyosis: A case report.

Although adenomyosis is a benign uterine disease, it can turn malignant in rare instances. Cystic adenomyosis is a rare variation of adenomyosis, arising from which 8 cases of clear cell carcinoma have been reported. However, to the best of our knowledge, there have been no previous reports describing the mechanism by which clear cell carcinoma develops from cystic adenomyosis. The present report documents a case of a 73-year-old woman who was referred to Kanazawa University Hospital (Kanazawa, Japan) because of cystic adenomyosis, with a solid part inside the cyst. The patient was diagnosed with cystic adenomyosis at Shonan Obstetrics and Gynecology Hospital (Hakusan, Japan) 17 years prior; however, the size of the cyst increased after menopause. Therefore, malignant transformation was suspected, which warranted simple abdominal hysterectomy and bilateral salpingo-oophorectomy. The final diagnosis of the present case was uterine corpus cancer, clear cell carcinoma, stage IA. Immunohistochemical staining revealed that the normal and transitional atypical epithelial cells lining the cyst wall, in addition to the clear cell carcinoma cells (which were inside mural nodules located on the cyst wall), were positive for 8-hydroxy-20-deoxyguanosine. This observation suggested the presence of chronic oxidative stress around the cystic adenomyosis. Therefore, the present case suggests the possible involvement of chronic oxidative stress in the malignant transformation of cystic adenomyosis to clear cell carcinoma. This mechanism of malignant transformation of cystic adenomyosis appears to be similar to that of the malignant transformation of endometriotic cysts. Therefore, if the size of the cystic adenomyosis increases after menopause or if the solid part appears in the cyst in future cases, then the possibility of malignant transformation should be considered.

Advancements in diagnosing oral potentially malignant disorders: leveraging Vision transformers for multi-class detection.

OBJECTIVES: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers. METHODS: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented. RESULTS: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938. CONCLUSIONS: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective. CLINICAL RELEVANCE: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier.

Exploring the role of SOX 2 and OCT 4 in the pathogenesis of gliomatosis peritonei: the clinicopathological profile of eleven cases.

Objective: Gliomatosis peritonei (GP) is a rare entity characterized by multiple mature glial tissue implants in association with ovarian teratomas in the peritoneum and omentum. To date, only 100 cases have been published. Not much is known about the origin, clinicopathological profile or prognosis of GP. SOX2 and OCT4 are recently recognized markers of embryonic stem cell differentiation. Here, the role of SOX2 and OCT4 in the pathogenesis of 11 cases of GP are reported and clinicopathological factors are described. Material and Methods: This was a retrospective study of six years duration (2017-2022). All the cases of GP were retrieved from archives, the diagnosis was confirmed and clinicopathological factors were noted. Immunohistochemical (IHC) investigation for glial fibrillary acid protein (GFAP) and S100 was noted wherever available. IHC for SOX2 and OCT4 was performed using an avidin-biotin technique. Results: There were 11 cases of GP identified. The median age was 29 years and 1/11 cases had nodal gliomatosis as well. There were eight cases of immature teratoma and three cases of mature cystic teratoma. SOX2 was positive in all foci of GP, while OCT4 was negative. These foci were also positive for GFAP and S100. Conclusion: A possibility of GP should be considered as a differential, clinically and radiologically, in cases of omental nodularity. Adequate sampling at the time of surgery is essential to rule out metastasis or growing teratoma syndrome. SOX2, a stem cell marker inducing neural differentiation, may play a crucial role in the development of GP in association with other transcription factors.

Malignant Transformation of an Ovarian Mature Cystic Teratoma to a Malignant Melanoma.

Ovarian mature cystic teratomas comprise tissue derived from all three germ layers and constitute 10-20% of all ovarian neoplasms. Malignant transformation of mature cystic teratomas (MCT) is very rare with an incidence of 0.17-2%. The most frequently reported malignancies include squamous cell carcinoma and adenocarcinoma. Herein, we describe a case of a 56-year-old female who presented with abdominal pain and underwent total abdominal hysterectomy with bilateral oophorectomy and omentectomy for a ruptured dermoid cyst. Histological examination showed nests of pleomorphic cells with prominent nucleoli and melanin pigment in the background of a mature cystic teratoma. These cells showed immunoreactivity for Melan-A and HMB-45, thus confirming the diagnosis of malignant transformation of a mature cystic teratoma to a malignant melanoma.

p53 exerts anticancer effects by regulating enhancer formation and activity.

The abnormality of p53 tumor suppressor is crucial in lung cancer development, and p53 may regulate target gene promoters to combat cancer. Recent studies have shown extensive p53 binding to enhancer elements. However, whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood. In the current study, we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout human bronchial epithelial cells (BEAS-2B). A total of 943 active regular enhancers and 370 super-enhancers (SEs) disappeared upon the deletion of p53, indicating that p53 modulates the activity of hundreds of enhancer elements. We found that one p53-dependent SE, located on chromosome 9 and designated as KLF4-SE, regulated the expression of the Krüppel-like factor 4 ( KLF4) gene. Furthermore, deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression, but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model. Subsequently, in TP53 knockout cells, the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency. Consistently, KLF4 expression also decreased in lung cancer tissues and cell lines. Overexpression of KLF4 significantly suppressed lung cancer cell proliferation and migration. Collectively, our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function. Therefore, our findings offer novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

Construction and Identification of a Human Colorectal Adenoma Epithelial Cell Line by SV40 Large T-Antigen Transfection.

BACKGROUND: Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions. AIMS: This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection. METHODS: Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval. CONCLUSION: We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.