High Risk Of Malignant Transformation Research Articles

Recurrence in Oral Leukoplakia: A Systematic Review and Meta-analysis.

The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy.

A complete course of photodynamic therapy reduced the risk of malignant transformation of oral leukoplakia

BackgroundPhotodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK. MethodsKaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics. ResultsOLK patients with older age (HR=1.032, P=0.018) and non-homogeneous lesion (HR=2.104, P=0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P=0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P=0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia. ConclusionsA complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation.

β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions.

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis-particularly in the ovary-is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.

Liver Transplantation for Adenomatosis: A Single-Center Experience

Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. To report a single-center experience of liver transplantation for diffuse adenomatosis. Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.

Efficacy and safety of the vebreltinib in patients with previously treated, secondary glioblastoma/IDH mutant glioblastoma with PTPRZ1-METFUsion GENe (FUGEN): A randomised, multicentre, open-label, phase II/III trial.

2003 Background: Although gliomas with mutated IDH have an improved prognosis compared to gliomas with wild-type IDH, IDH-mutant gliomas carry a high risk of malignant transformation from low-grade gliomas into high-grade gliomas within 10 years, resulting in poor prognosis. However, effective targeted drugs for high-grade gliomas are still lacking. Here, we report data from the FUGEN study of Vebreltinib, the first completed phase II/III trial of sGBM / IDH mutant glioblastoma patients with previously treated, PTPRZ1-MET Fusion gene positive. Methods: In this open-label, phase II/III trial, we randomly assigned, in a 1:1 ratio, 84 patients with Histologically confirmed secondary GBM or IDH-mutant GBM to receive twice-daily oral vebreltinib in 300 mg dose or the investigator's choice of chemotherapy (temozolomide [100-150 mg/m2/day, 7days on followed by 7 days off ] or cis-platinum [80-100 mg/m2 for 3 days] combined with etoposide [100mg/m2/day for 3 days]) every 28 days. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results: 42 patients of the vebreltinib group and 39 patients of the chemotherapy group were included in the full analysis set. After a median follow-up of 4.44 months, the median OS in the vebreltinib group and chemotherapy group was 6.31 months (95% CI, 4.44-8.77) and 3.38 months (95% CI, 2.37-4.27), respectively. The HR for OS was 0.52 (90% CI, 0.32-0.85; P = 0.009). The median PFS in the vebreltinib group and chemotherapy group was 1.87 months (95% CI, 1.41-2.76) and 1.05 months (95% CI, 0.95-1.77), respectively. The HR for PFS was 0.54 (95% CI, 0.33-0.88; P = 0.014). No significant differences were observed in ORR (9.5% vs. 2.6%) for the vebreltinib group and chemotherapy group. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the vebreltinib group, as compared with 12.2% of those in the chemotherapy group. No treatment-related deaths were observed. Conclusions: These results of the FUGEN trail support the use of vebreltinib as the first target therapy in patients with previously treated, PTPRZ1-MET fusion gene positive, secondary glioblastoma / IDH-mutant glioblastoma, and shed light on a novel therapeutic pathway in the landscape of IDH-mutant high-grade gliomas. Clinical Trials Information: NCT06105619 and ChiCTR2300077783 Research Funding:Beijing Pearl Biotechnology Co., Ltd. and Avistone Biotechnology Limited. Clinical trial information: NCT06105619 .

Clinical, histopathological characteristics and malignant transformation of proliferative verrucous leukoplakia with 36 patients: a retrospective longitudinal study

BackgroundProliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL.MethodsThis study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients.ResultsThe cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan–Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05).ConclusionThe main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.

Leukoplakia with Diverse Grades of Epithelial Dysplasia – A Case Series and Review of Literature with Updated Management Protocol

Oral leukoplakia is considered the most potentially malignant disorder of the oral cavity, with a high risk of malignant transformation. Based on the clinical manifestation, it has been classified as a homogeneous and non-homogeneous variant. It has been considered predominantly a white lesion of the oral cavity that cannot be classified under any other definable lesions. Leukoplakia is a term used to describe the lesion clinically. There are various components responsible for the threatening change of oral leukoplakia. The clinical diagnosis of leukoplakia is confirmed by histopathology, which commonly indicates intense epithelial dysplasia. This manuscript describes a series of cases diagnosed clinically as leukoplakia and their grades of epithelial dysplasia, a Review of literature about etiology and the key pathogenesis behind it, risk determinants for malignant transformation, chair side investigation for epithelial dysplasia, and updated management protocol.

Knowledge About the Importance of Early Diagnosis and Treatment of Oral Potentially Malignant Disorders Among the South Indian Population: An Institutional Retrospective Study.

The significant malignant transformation rates of oral potentially malignant disorders (OPMDs) demand early diagnosis and proper management of OPMDs not only to reduce symptoms but also to prevent their aggressive outcomes. This retrospective study aimed to quantify the need for patient-related awareness in identifying OPMDs by quantitatively evaluating the association between the type of referral in OPMD cases. This study also aims to analyze the association between gender and types of referral in OPMDs. The sample size of n=1577 (500-leukoplakia, 500-oral submucous fibrosis (OSMF), 500-lichen planus, 77-lichenoid reaction) was considered in the present retrospective study. Data regarding the sample cases were extracted from the common patient database of the Saveetha Dental College and Hospitals from June 2019 to February 2024. Random sampling method was used, and the OPMDs were categorized into two groups based on the chief complaint as self-referred and specialist-referred cases. The segregated data were tabulated in Microsoft Excel (Microsoft® Corp., Redmond, WA) and then exported to IBMSPSSStatistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States) for statistical analysis. Pearson's chi-square test was conducted to analyze the association of referral type, OPMDs, and gender. Out of 1577 OPMD cases, 929 (58.9%) were specialist-referral cases and 648 (41.1%) were self-referral cases. Among OPMDs, lichen planus was the most self-referred 310 (62%) and leukoplakia was the most specialist-referred 470 (78.6%) category. This study found a statistically significant correlation between the type of referrals and the type of OPMDs (p=0.000). Self-referral was more commonly observed in females (23.3%) than males (17.8%) in general and among all categories of OPMDs except lichenoid reactions. This observation was also statistically significant (p=0.000). Conclusion: Among OPMDs selected in the present study, lichen planus and OSMF were more self-referred and leukoplakia cases were mostly specialist-referred. This study highlights the need of detecting less symptomatic lesions, such as leukoplakia, which has a high risk of malignant transformation. The lack of awareness about the identification of OPMDs among patients can result in delayed diagnosis and treatment, which may further result in progression to aggressive outcomes.

Дифференциальная диагностика невусов и меланом хориоидеи по данным ОКТ

The article presents the study results of 64 patients with suspicious (progressive) nevi (n = 42) and initial choroid melanomas (n = 22, of which n = 3 had anamnesis of choroid nevus). Ultrasound examination, digital photoregistration of the fundus and OCT were done for all patients. According to the OCT data it was possible to identify diagnostic criteria that help distinguish of suspicious nevi including those with a high risk of malignant transformation from initial choroid melanomas. First of all these are the preservation of the Bruch membrane and the presence of druses. While malignant transformation of suspicious nevi was characterized by shape asymmetry of the enlarged “choroidal complex”, dilation of large choroidal vessels around the nevus, the presence of RPE detachment and the presence of hyperreflective intraretinal inclusions. Criteria of initial choroid melanomas were violation of the integrity of the Bruch membrane, rounded cavities in the inner layers of the choroid, deposits at the level of RPE, edema and/or rupture of the photoreceptor layer. Keywords: suspicious choroid nevus, choroid melanoma, OCT

Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.

Diagnosis of differentiated dysplasia as a variant of oral epithelial dysplasia.

The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology. Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia. Biopsies were assessed for dysplasia and its grade. Available brush cytology findings were obtained from clinical records. We included 159 biopsies from 112 patients (33% differentiated dysplasia; 27% keratosis without dysplasia; oral epithelial dysplasia with atypia of mild, moderate and severe degree including invasive cancers in 9%, 8% and 7%, respectively). Keratin 13 loss and keratin 17 gain were higher in differentiated-dysplasia cases (p < 0.0001), which had the highest hypergranulosis frequency. Keratin 17 expression was associated with higher malignant-transformation rates (p = 0.0028). The transformation rate and time were comparable between dysplasia with atypia and differentiated-dysplasia cases, which had higher progression rates and shorter time periods than keratosis cases without dysplasia (p = 0.08). Cytology prior to differentiated dysplasia all indicated normal oral mucosa. Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation.

Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis.

Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oral potentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinical practice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF to outline the clinical behavior and challenges in the management of this high-risk group in clinical practice. We retrospectively analyzed cases of six Indian patients (four with OSF) managed over a period of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, medical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits, the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or when surgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twice daily was initiated. All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesions were either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional or systemic metastasis. Despite thorough interventions, the patients died of, or with the disease. The occurrence of two or more oral potentially malignant disorders poses challenges in patient management and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to assess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.

Proliferative Verrucous Leukoplakia: An Update

Objectives: Proliferative verrucous leukoplakia was first described by Hansen et al. in 1985. It is a rare form of oral leukoplakia with a high risk of malignant transformation. A review of the scientific literature indicates that there is no consensus on the management and follow-up of proliferative verrucous leukoplakia. This article aims to provide an update on the epidemiological, clinical, histological and immunohistochemical, diagnostic, treatment and follow-up data on the disease. Materials and Methods: We performed a narrative review by searching the Pubmed and Google Scholar databases using keywords. Results: 93 out of 446 selected articles were selected for analysis. The majority of affected patients are women. The lesions are multifocal and usually occur on the gingiva and alveolar mucosa. The aetiology is idiopathic. The diagnosis is retrospective and based on the history of the disease. Apart from mapping the lesions using repeated biopsies to detect a malignant area progression, there is no recommended treatment to cure the disease. Conclusion: The current understanding of this entity is based on the analysis of retrospective studies with weak scientific evidence. Expert recommendations regarding follow-up and management would facilitate better control of recurrence and malignant transformation rates.

The Magic Triangle in Oral Potentially Malignant Disorders: Vitamin D, Vitamin D Receptor, and Malignancy.

OPMDs (oral potentially malignant disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of various diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also suggest a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD and investigate their potential association and ramifications for clinical management of OPMDs.

Research progress in the diagnosis and management of proliferative verrucous leukoplakia

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.

876P Gene expression analysis in oral potentially malignant disorders (OPMD) with dysplasia identifies patients at high risk of malignant transformation

876P Gene expression analysis in oral potentially malignant disorders (OPMD) with dysplasia identifies patients at high risk of malignant transformation

PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma.

Lower-grade glioma (LGG) is a primary intracranial tumor that carry a high risk of malignant transformation and limited therapeutic options. Emerging evidence indicates that the tumor microenvironment (TME) is a superior predictor for tumor progression and therapy response. PLEKHA4 has been demonstrated to be a biomarker for LGG that correlate with immune infiltration. However, the fundamental mechanism by which PLEKHA4 contributes to LGG is still poorly understood. Multiple bioinformatic tools, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA2), Shiny Methylation Analysis Resource Tool (SMART), etc., were incorporated to analyze the PLEKHA4. ESTIMATE, ssGSEA, CIBERSORT, TIDE and CellMiner algorithms were employed to determine the association of PLEKHA4 with TME, immunotherapy response and drug sensitivities. Immunohistochemistry (IHC)-based tissue microarrays and M2 macrophage infiltration assay were conducted to verify their associations. PLEKHA4 expression was found to be dramatically upregulated and strongly associated with unfavorable overall survival (OS) and disease-specific survival (DSS) in LGG patients, as well as their poor clinicopathological characteristics. Cox regression analysis identified that PLEKHA4 was an independent prognostic factor. Methylation analysis revealed that DNA methylation correlates with PLEKHA4 expression and indicates a better outcome in LGG. Moreover, PLEKHA4 was remarkably correlated with immune responses and TME remodeling, as evidenced by its positive correlation with particular immune marker subsets and the putative infiltration of immune cells. Surprisingly, the proportion of M2 macrophages in TME was strikingly higher than others, inferring that PLEKHA4 may regulate the infiltration and polarization of M2 macrophages. Evidence provided by IHC-based tissue microarrays and M2 macrophage infiltration assay further validated our findings. Moreover, PLEKHA4 expression was found to be significantly correlated with chemokines, interleukins, and their receptors, further supporting the critical role of PLEKHA4 in reshaping the TME. Additionally, we found that PLEKHA4 expression was closely associated with drug sensitivities and immunotherapy responses, indicating that PLEKHA4 expression also had potential clinical significance in guiding immunotherapy and chemotherapy in LGG. PLEKHA4 plays a pivotal role in reshaping the TME of LGG patients, and may serve as a potential predictor for LGG prognosis and therapy.

SERUM MIR-181А AND MIR-25 LEVELS IN PATIENTS WITH BREAST CANCEROR A BENIGN BREAST DISEASE

Circulating miR-181а and miR-25, which reflect regulation of the expression of carcinogenesis-related genes, were assayed in patients with invasive carcinoma of no specific type (ICNT) or benign diseases of the breast (BDBs) and in people without pathologies of the mammary gland (controls). MiR-181а expression level proved to be higher compared to control in patients with fibroadenoma and adenosis with low but not high risk of malignant transformation as well as in patients with luminal HER2-negative type B (Lum B HER2–), HER2-positive type (HER2+) and triple-negative breast cancer (TNBC) than in the controls and luminal-type (Lum A) breast cancer. MiR-25 expression level prevailed in patients with Lum B HER2- compared to control, Lum A and TNBC; in patients with TNBC compared to Lum A. Thus, MiR-181а and miR-25 expression levels may be risk indicators of malignant transformation in some patients with BDBs, whereas in patients with ICNT, these levels reflect pathological processes of different directions within the tumor.

Analysis on the Knowledge about Oral Potentially Malignant Disorders of a Male Motorcycle Community in Indonesia

Abstract Background Oral potentially malignant disorders (OPMDs) are a group of oral lesions or conditions with a higher risk of malignant transformation. OPMD affects 4.47% of people worldwide, with predilection in males. The high tendency of frequent tobacco smoking and alcohol consumption may lead the male motorcycle community to have a higher risk for developing OPMD and malignant transformation. Objectives This article determines the level of knowledge about OPMD within a male motorcycle community. Methods This study uses a survey research design that is a questionnaire-based and descriptive study. Data were obtained using a Google Form, and IBM SPSS was used for analysis. Simple random sampling is the sampling method applied. The total knowledge score is divided into three levels, low (0–4), moderate (5–9), and high (10–15). Results The questionnaire was finished by 60 people entirely. All respondents (100%) were men, and the majority (83.00%) was aged between 20 and 21. A total of 26 respondents (43.30%) had moderate knowledge levels, followed by 21 with high knowledge levels (35.0%), and 13 with low knowledge levels (21.70%). Conclusion The majority of the male motorcycle community (43.30%) has a moderate knowledge level regarding OPMD. This study indicates the need for educational measures to improve awareness regarding OPMD in a high-risk community.

Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.