High Risk Of Malignant Transformation Research Articles

A Case of a Beta-Catenin-Activated Hepatic Adenoma in a Male Patient With Familial Adenomatous Polyposis

Hepatocellular adenoma is a benign liver tumor often diagnosed incidentally in women of reproductive age who are taking oral contraceptives. In this study, we present a unique case of an 18-year-old man with known familial adenomatous polyposis who presented with sepsis in the setting of a recent total proctocolectomy and was incidentally found to have multiple large hepatic lesions. A biopsy of a liver lesion confirmed the diagnosis of a beta-catenin-activated hepatic adenoma. To the best of our knowledge, this is the first known case of beta-catenin-activated hepatic adenoma in a patient with a known familial adenomatous polyposis mutation. Beta-catenin is one of the many subtypes of hepatocellular adenomas, which carries a high risk of malignant transformation.

Review: recent trends in management of oral lichen planus

Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disease, associated with altered cell‐mediated immunological function. It has been characterised by long‐term evolution, repeated exacerbations, sometimes painful and resistant to treatment, or even all of these. OLP significantly affects quality of patient's life. There is a higher risk of malignant transformation accompanied with OLP and similar appearing oral lichenoid lesions. Current OLP therapy aims at eliminating all mucosal‐related lesions reduce symptomatology and decrease the risk of oral cancer. This review summarizes recent treatment modalities used in the management of OLP which includes corticosteroids, immunomodulatory agents, retinoids, ultraviolet irradiation and/or laser therapy, herbal remedies. In addition, focus is also given upon adopting holistic approach in such patients by emphasizing on stress management.

The Genetic and Immunologic Landscape Underlying the Risk of Malignant Progression in Laryngeal Dysplasia

(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia). Two pathologists independently analyzed the presence of tumor-infiltrating lymphocytes in LDy pre-embedded paraffin-fixed specimens. The RNA-based next-generation sequencing panel OIRRA was used to evaluate the expression of 395 genes related to immune system activation. (3) Results: High TILs are significantly correlated with a higher risk of malignant transformation. The non-brisk pattern was significantly associated with an 86% reduced risk of malignant progression (OR = 0.16, 95% CI: 0.03-0.5, p = 0.008). TILs showed a highly positive correlation with CCR6, CD83, HLA-DPB1, MX1 and SNAI1, and they were inversely correlated with CD48, CIITA, CXCR4, FCER1G, IL1B, LST1 and TLR8. (4) Conclusions: TILs have a great potential to identify high-risk progression dysplasia and thus to define surveillance protocols and prevention programs.

Transcriptomic Analysis of Hepatitis B Infected Liver for Prediction of Hepatocellular Carcinoma.

Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.

FGFR1 is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridizationin the tongue squamous cell carcinoma cases. Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p=0.016, HR: 7.3, 95% CI: 1.4-37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease-free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p=0.024; HR: 4.9, 95% CI: 1.2-19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n=8) showed markedly impaired overall survival (p=0.020; HR: 6.4, 95% CI: 1.3-31.1) and disease-free survival (p=0.001, HR: 13.0, 95% CI: 3.0-55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p=0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease-free survival. Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

Challenges in the Classification of Oral Submucous Fibrosis and Proposing a New Classification Based on Systematic Review of Literature.

Oral submucous fibrosis is one of the common oral potentially malignant disorders that can result in severe morbidity. Due to its widespread involvement in the oral cavity and high risk of malignant transformation, the diagnosis and treatment of this disease at an early stage is essential to prevent further complications. This research was carried out to review various classification systems of oral submucous fibrosis documented in the literature to date, including their benefits and drawbacks, thus focusing on a need to discover some reliable classification systems. An electronic search of the published English literature was performed without publication year limitation in PubMed/Medline, Science Direct, Web of Science, Google Scholar, and Scopus databases using keywords like ('Oral submucous fibrosis' OR 'Oral submucous fibroses'), AND ('Classification' OR 'Grade' OR 'Stage'), AND ('Clinical', OR/ AND 'Histological', OR/AND 'Functional') following PRISMA guidelines. A manual search of all related Dental and Medical journals was also performed. We also checked the reference lists of the relevant articles for any other possible information on the subject. The search strategy revealed 31 relevant articles and it could be appreciated that oral submucous fibrosis has been classified in seven different ways. Each system is enclosed with its own limitations and benefits. From this research, it can be concluded that despite the existence of several classification systems for oral submucous fibrosis, at present, no classification scheme is considered to be reliable that could help in the accurate assessment of the progression of the disease and classifying oral submucous fibrosis still remains a challenging task for clinicians, surgeons, and pathologists. We have postulated a proposed new classification system based on our literature research, but still robust research is needed in this aspect.

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

BackgroundOwing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin.MethodsMicrobiota composition was determined through 16S rRNA V3–V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as “tri-part samples”) in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria.ResultsPrevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells.ConclusionThis report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

Diabetes mellitus and the risk of progression or malignancy of pancreatic cystic neoplasms in patients undergoing surveillance: A systematic review and meta-analysis

Background/objectivesPatients with pancreatic cystic neoplasms (PCN) generally undergo surveillance by cross-sectional imaging or endoscopic-ultrasound due to their pre-malignant potential. Appearance of certain cyst characteristics during surveillance is associated with aggressive behavior or presence of malignancy. Patient characteristics associated with progression or induction of malignancy in PCN is unclear from current studies. We performed this meta-analysis to determine the patient characteristics associated with progression or malignancy in patients with PCN who undergo surveillance. MethodsWe performed a systematic research of several electronic databases for all the studies on surveillance of PCN which reported demographic data of patients who had progression or malignancy and controls. We calculated Risk ratio (RR) or Hazard ratio (HR) with 95% confidence interval (CI) for each variable. Mantel- Haenszel method or Inverse-variance model was used to pool data of progression or malignant transformation into fixed or random effect model meta-analysis. Results11observational studies, 4 assessing risk factors for malignancy (3955 patients) and 7 evaluating risk factors for progression of PCN (3144 patients) were included in the meta-analysis. Diabetes mellitus was associated with higher risk for malignant transformation as well as progression of PCN (RR = 1.54, CI 1.23, 1.92). Advanced age was associated with higher risk of progression. Male gender had higher risk for malignant transformation but not progression of PCN. ConclusionDiabetes is associated with an increased risk of both malignancy and progression of PCN in patients who undergo surveillance. Advanced age is also associated with higher risk of progression of PCN.

S71 The Natural History of Pancreatic Cystic Lesions in Liver Transplant Recipients: A Systematic Review and Meta-Analysis

Introduction: Pancreatic cystic lesions (PCLs) exhibit a wide array of clinicopathologic behavior. As such, risk stratifying these is important to prevent the progression to malignancy. Theoretically PCLs in liver transplant (LT) recipients are at increased risk of accelerated carcinogenesis in the setting of lifelong immunosuppressive medications. With improvements in surgical outcomes, LT patients are living longer and understanding the incidence and natural course of these lesions is paramount. As such we conducted a systematic review and meta-analysis to investigate the risk of malignant progression and outcomes of PCLs in LT recipients. Methods: Multiple databases (PUBMED, Embase, the Cochrane Library) were searched for studies looking at PCLs in post-LT patients from inception until February 2022. Data was extracted to calculate pooled estimates and risk ratios using a random effects model. Primary outcomes were the incidence of PCLs in transplant recipients and progression to malignancy. Secondary outcomes included outcomes of those undergoing surgical resection for progression and change in size over time. There was moderate heterogeneity of our sample. Results: 12 studies met inclusion criteria (17,862 patients with 1,411 PCLs). The pooled proportion of new PCL development in post-LT patients was 68% (95% CI, 42 – 86, I2 94%) over a follow up of 3.7±1.5 years. The relative risk of developing PCL in LT recipients compared to non-LT recipients was associated with a significant 67% reduction (RR 0.33; 95% CI, 0.14 – 0.79, I2 93.91, p = 0.01). Among 4158 patients receiving LT, 295 developed PCL and 4 of them progressed to malignancy; the pooled progression to malignancy was 1% (95% CI, 0 – 2, I2 0%) (Figure). LT was associated with a significant 71% reduction in relative risk of undergoing surgical resection (RR 0.29; 95% CI, 0.09 - 0.93, I2 0%, p = 0.04). Conclusion: Compared to non-transplant patients, incidental PCLs in LT patients do not carry a higher risk of malignant transformation. In the setting of immunosuppressive medication, the risk of malignant progression appears to be negligible, and these patients can be followed like non-LT patients based on guidelines. Furthermore, our findings emphasize that incidental PCLs should not preclude a LT evaluation.Figure 1.: Individual estimates and pooled proportions of progression of pancreatic cystic lesions to malignancy in post liver transplant patients

Evaluation of the classification and clinical characteristics of oral lichen planus and its treatment effect in different clinical types: A retrospective study

PurposeOral lichen planus (OLP) is an intractable chronic inflammatory disease associated with dyskeratosis. This study aimed to investigate the clinical features of OLP at the initial diagnosis and classified it using the clinical visual examination type classification. Furthermore, we evaluated whether the clinical characteristics and effectiveness of symptomatic treatment differ between the typical reticular type and other types of OLP. MethodsWe evaluated the age, sex, chief complaints, clinical morphological forms, lesion sites, cytological and histopathological findings, therapeutic strategies, and therapeutic responsiveness of 132 patients with OLP. ResultsOf 132 patients, there were 42 men and 90 women (mean age, 66.4 ± 13.0 years). The buccal mucosa was the most affected site (n = 95). The reticular form was the most common clinical morphological form (n = 124). Biopsy was performed in 48 patients. The erosive form was the most common among the biopsied lesions. Regarding therapeutic strategies, topical steroids were prescribed to 85 patients, 47 of whom experienced symptomatic relief and 38 showed no changes in symptoms. The rates of symptomatic relief following topical steroid use were 70.4% and 15.9% for the reticular and erosive forms, respectively. In patients with erosive and plaque-like forms, symptomatic relief with topical steroid use was difficult to achieve, whereas in those with other forms, a moderate response was observed. ConclusionTopical steroids are often ineffective in patients with erosive or mixed forms, and these clinical morphological forms are associated with a higher risk of malignant transformation than the other forms. Therefore, early histological examination is important.

Single-cell transcriptomics dissects premalignant progression in proliferative verrucous leukoplakia.

Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL. We performed single-cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression. By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation. Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes.

MULTI-DISCIPLINARY INTERVENTION FOR LABIAL FUSION IN A CASE OF VULVAL LICHEN PLANUS.

Vulvo-vaginal lichen planus is a very distressing and rare forms of non-venereal genital dermatoses. Erosive variants of Lichen planus often have a protracted course and has a higher risk of malignant transformation. This case was a 53-year- old woman, previously diagnosed with lichen planus on conservative treatment, who now presented with symptomatic labial adhesions and urinary complaints like urgency, frequency and poor urine stream. Clinical examination revealed normally developed labia majora, partially but extensively fused labia minora including the clitoral hood. Urethral opening was not visualised, while a small vaginal orifice was seen with no ulcerations. A multi-disciplinary team consisting of urologist and plastic and cosmetic surgeon dissected out the labial adhesions with the electrocautery and reconstructed the vaginal and urethral openings. Cystoscopy followed by urethral dilatation was done for urethral narrowing. Postoperatively, on following up the patient the adhesions were completely separated, and the area healed well. No recurrences were noted. Though aggressive management with topical steroids and other measures often improves symptoms on short term basis, few patients may require long term management by multi-disciplinary team to optimize the outcomes.

CCR5 as a Prognostic Factor in Lower-Grade Glioma is Involved in the Remodeling of the Tumor Microenvironment.

Background: Lower-grade gliomas (LGGs) carry a high risk of malignant transformation, leading to severe neurologic deterioration and ultimately, death. The tumor microenvironment (TME) plays an essential role in tumor maintenance, progression, and immunotherapy resistance. Therefore, the LGG TME deserves comprehensive exploration for a novel therapeutic target. Methods: The ESTIMATE algorithm was used to estimate infiltrating stromal and immune cells of LGG patients obtained from the Cancer Genome Atlas (TCGA) database. Kaplan–Meier analysis was performed to classify survival differences. TME-related differentially expressed genes were identified between the low- and high-immune/stromal groups. Hub genes were screened by constructing protein–protein interaction networks and performing the Cox regression analysis. Differential analysis, survival analysis, gene set enrichment analysis, and clinical relevance analysis specific to hub genes were evaluated by using the TCGA and the Chinese Glioma Genome Atlas datasets, and the results were validated by qRT-PCR, Western blotting, and immunohistochemistry in tissues from LGG patients. Results: The immune and stromal components in TME were negatively related to patient prognosis. Differentially expressed genes sharing immune score and stromal score were mainly involved in the immune response. C-C chemokine receptor type 5 (CCR5), as only a hub gene, was significantly higher in LGG patients than normal patients and negatively correlated with the prognosis of patients. High-expression CCR5 was positively related to immune-related and tumor progression pathways. CCR5 protein expression was higher in LGG with isocitrate dehydrogenase wildtype. Validated results showed that CCR5 was upregulated in LGG tissues at mRNA and protein levels and could affect immune cell infiltration. These results suggested that CCR5 was a potential indicator for the status of TME. Conclusion: Glioma cells remodel the immune microenvironment through the high expression of CCR5 and lead to a poor prognosis in patients with LGG. The inhibition of CCR5 may contribute to the efficacy of LGG immunotherapy.

Clinicopathological characteristics of oral squamous cell carcinoma arising from oral submucous fibrosis: A systematic review.

Oral submucous fibrosis (OSMF) is considered to be a potentially malignant oral disorder with high risk of malignant transformation. Oral squamous cell carcinoma (OSCC) arising from OSMF has peculiar clinical and histopathological features. To assess the clinicopathological features of OSCC arising in the background of OSMF in an attempt to identify the patients with OSMF who are at increased risk of developing OSCC. A systematic review was performed based on PRISMA guidelines to include articles published until May 2021 in English, relating the clinicohistopathological characteristics of OSCC arising from OSMF (OSMF-OSCC) or OSMF associated with OSCC (OSCC-OSMF). All the eligible articles were analyzed and relevant data were extracted. Seventeen articles were included for systematic review after following strict inclusion and exclusion criteria. The malignant transformation rate of OSMF-OSCC ranged from 1.9 to 9.13 and the prevalence of OSCC-OSMF ranged from 2.8 to 66. The mean age of the patients ranged from 36.6 years to 47.2 years and buccal mucosa was the common site to be affected. Majority of the OSCC-OSMF was well-to-moderately differentiated and majority of them did not metastasize to the lymph nodes. OSCC associated with OSMF presents at a younger age with early tumor stage, better differentiation, and better prognosis when compared to OSCC not associated with OSMF. However, more multicentric prospective studies with large sample size are required to determine the true biologic behavior of OSCC arising in the background of OSMF to establish less aggressive treatment strategies considering them as a separate entity.

Unmet Needs and Perspectives in Oral Cancer Prevention

Simple SummaryOral cavity is the most common site of head and neck cancer which is ranked as the eighth most common cancer worldwide. Oral cancer treatment is often associated with significant morbidity and is sometimes ineffective. These cancers, mainly due to tobacco and alcohol consumption, can develop from oral potentially malignant disorders, the most common of which is oral leukoplakia. Some of these oral potentially malignant disorders disappear, while others will transform to oral cancer. Patients may also develop cancer in the field of cancerization. Unfortunately, except for the surgical excision of lesions with dysplasia, there is no effective intervention to effectively prevent transformation or cancer development in the field of cancerization. Moreover, no standardized biomarker has been clearly identified as sufficient to predict malignant transformation. In this article, several experts discuss the main challenges in oral cancer prevention, in particular the need (i) to define new a new classification system integrating cellular and molecular features aiming (ii) at better identifying patients at high risk of malignant transformation, and (iii) at developing treatment strategies to prevent their malignant transformation of oral potentially malignant disorders.Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.

Oral potentially malignant disorders: A clinician’s perspective

The ability to predict which oral potentially malignant disorder will progress to squamous cell carcinoma remains the ultimate challenge facing clinicians managing patients with oral diseases. Currently oral epithelial dysplasia graded by pathologists holds a strong bearing on the risk of malignant transformation of a lesion; with high-grade lesions indicative of higher risk of malignant transformation, while low-grade lesions very rarely transforming to malignancy. However, repeated studies and real-world cases have shown that oral squamous cell carcinoma can occur in lesions with no epithelial dysplasia. There still remains an unmet need among clinicians managing patients with oral diseases for effective tools to predict risk of malignant progression. This presentation will aim to explore the real-world dilemmas faced in clinical diagnosis and management of patients with oral potentially malignant disorders and discuss developments in technology including diagnostic adjuncts and artificial intelligence that may assist in resolving this clinical dilemma.

Overexpression of PTPRZ1 Regulates p120/β-Catenin Phosphorylation to Promote Carcinogenesis of Oral Submucous Fibrosis.

Background Oral submucous fibrosis (OSF) is a potentially malignant disease of the oral cavity. New molecular predictors are needed to identify the high risk of malignant transformation in potentially malignant oral lesions. Our purpose is to explore PTPRZ1 and p120/β-catenin pathogenesis in the carcinogenesis of OSF to identify novel drug targets. Methods The expression of PTPRZ1, p120, and β-catenin in clinical tissues was detected. Then, PTPRZ1, p120, β-catenin, RhoA, Rac1, CDC42, cyclin D1, and c-myc expressions were detected by qRT-PCR and western blot. CCK-8 was applied to measure hOMF cells viability. Wound healing and transwell assay were applied to measure cell migration and invasion. Western blot and IF detected the distribution of p-p120 and p-β-catenin. Tumor formation experiment explored PTPRZ1 effects on OSF. Results PTPRZ1, p120, and β-catenin were abnormally expressed in cancer tissues. PTPRZ1 regulated the phosphorylation of p120/β-catenin. Western blot and IF showed that in the oe-NC group, p-p120 and p-β-catenin were expressed in the cell membrane. p-p120 and p-β-catenin were expressed in the cytoplasm and nucleus of the oe-PTPRZ1 group. In vitro experimental results revealed overexpression of PTPRZ1 and β-catenin, and silencing of p120 promoted cell proliferation, migration, and invasion. The tumor volume and weight in the sh-PTPRZ1 group were significantly reduced. IHC revealed the positive rate of PTPRZ1 was also low. Conclusions Overexpression of PTPRZ1 regulated the phosphorylation of p120/β-catenin to promote OSF malignancy.

Immunohistochemical staining patterns of p53 predict the mutational status of TP53 in oral epithelial dysplasia

Next-generation sequencing of oral squamous cell carcinoma (OSCC) has revealed TP53 as the most frequently mutated gene in OSCC mutually exclusive with human papillomavirus infection. Oral epithelial dysplasia (OED) is defined as a precancerous lesion of OSCC by the current World Health Organization (WHO) classification; therefore, it is assumed that TP53 mutations occur in early precancerous conditions such as OED. Here, we conducted an integrated analysis of TP53, including whole coding sequencing of TP53, FISH analysis of the 17p13.1 locus, and immunohistochemical analysis for p53 (p53-IHC), in 40 OED cases. We detected 20 mutations in 16 (40%) OED cases, and four cases, each harbored two mutations. FISH analysis revealed six of 24 cases (25%) had a deletion on 17p13.1, and four cases had concurrent TP53 mutations and 17p13.1 deletion (2-hit). Also, the increased frequency of TP53 mutations in higher degrees of OED implies acquisition of the mutation is a major event toward OSCC. p53-IHC revealed that overall cases could be categorized into four patterns that correlate well with the mutational status of TP53. Especially, two patterns, broad p53 expression type (pattern HI) and p53 null type (pattern LS), strongly correlated with a missense mutation and nonsense mutation, respectively. Furthermore, seven of the 40 cases progressed to SCC, and six of these seven cases presented pattern HI or LS. Therefore, patterns HI and LS have a high risk for malignant transformation if excisional treatment is not performed irrespective of the dysplasia grade. Although the current WHO classification mainly focuses on morphological criteria for the diagnosis of OED, interobserver discrepancy appears in some instances of the OED diagnosis. Our immunohistochemical analysis supports a more accurate pathological diagnosis for OED in cases of low dysplastic changes or of differential diagnosis with non-dysplastic lesions.

A clinical signature predicting the malignant transformation of inflammatory myofibroblastic tumor in the head and neck.

BackgroundInflammatory myofibroblastic tumors in the head and neck (HNIMTs) sometimes show aggressive clinical features and can be diagnosed as HNIMT with malignant transformation.MethodsThe clinicopathological features of 45 HNIMTs with or without malignant transformation were retrospectively investigated. Logistic regression and receiver operating characteristic analysis were used to establish the predictive model.ResultsHNIMT with malignant transformation was associated with worse prognosis. HNIMT with a tumor size of >4.4 cm, tumors located in the maxillary sinus, or a preoperative neutrophil‐to‐lymphocyte ratio (NLR) greater than 1.958 were associated with higher chance of malignant transformation, with an AUC value of 0.9189. Postoperative radiotherapy could benefit HNIMT patients with high risk of malignant transformation.ConclusionsHNIMT patients with a tumor size of >4.4 cm, tumors located in the maxillary sinus, and a preoperative NLR over 1.958 were associated with a higher risk of malignant transformation. These patients can benefit from postoperative radiotherapy.