Early Detection Of Malignant Transformation Research Articles

Developing cell-free DNA (cfDNA) epigenetic signature (ep-Sig) for early detection of malignant transformation of intraductal papillary mucinous neoplasms (IPMN).

616 Background: Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers with poor outcomes. Around 20% arise from premalignant lesions (PML) including IPMN. Current guidelines recommend risk stratifying IPMN based on the location, size, and imaging characteristics after first diagnosis, followed by endoscopic ultrasound (EUS) in high-risk populations, and annual or bi-annual imaging. This approach can be improved with cfDNA testing. Traditional mutation testing in cfDNA is not useful secondary to their poor prevalence/detection rates. We propose ep-Sig to improve surveillance and early detection of PDA transformation. Methods: We curated an 11-gene cfDNA ep-Sig from the literature with a proven role in the malignant transformation of IPMN. Evidence suggests that epigenetic changes in every gene of this panel have a role in carcinogenesis in IPMNs. We compared RNA and gene expression of the genes in this ep-Sig between normal (NT) and PDA tissues using a web-based tool, TNMplot.com that uses the data from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories was used create this tool. It uses Mann-Whitney or Kruskal-Wallis tests to compute statistical significance. We used cell-free epigenome atlas (CFEA) database to examine the prevalence of these markers in cfDNA of PDA patients. Results: RNA expression of all the genes from the ep-Sig combined was significantly lower in PDA than NT (0.45, p=3.13e-26). Gene expression was 8/11 genes was lower in PDA tissues than NT (0.44, p=3.13e-26). The other 2 genes were not detected in the tested samples. Prevalence of all the markers in ep-Sig was > 90%. Conclusions: Our proposed ep-Sig has a high prevalence in PDA patients and has reliable preliminary evidence in tissues suggesting its diagnostic value. This study is the first step in developing non-invasive cfDNA testing with the potential to improve the current surveillance strategies for IPMN pending larger prospective studies.

Giant Congenital Melanocytic Naevi in Newborns: A Case Series

Giant Congenital Melanocytic Naevi (GCMN) is a very rare condition that mostly occurs due to an oncogenic mutation involving the NRAS (neuroblastoma RAS viral oncogene homologue) gene. GCMNs can be clinically diagnosed due to their typical features, but histopathology confirms the diagnosis. GCMN has a high propensity for transforming into malignant melanoma and leptomeningeal melanocytosis, leading to neurological deficits such as epilepsy and neurofibromatosis. As it is associated with Central Nervous System (CNS) melanosis, Magnetic Resonance Imaging (MRI) of the brain and spine is crucial. Here, three cases are reported of the babies born with GCMN from August 2022 to July 2023 in a tertiary care hospital among a total of 11,915 live births, where the incidence is much higher than found in the literature. Present series describes three cases with GCMN, including clinical features, MRI findings, short-term outcomes, risk factors, and modalities of the management. All three cases showed extensive blackish pigmented patches involving most of the body surface and MRI evidence of Neurocutaneous Melanosis (NCM). The third baby succumbed to death due to fulminant sepsis on day 2 of life. Management of GCMN requires a multimodal approach, including medical, surgical, chemotherapeutic, palliative, and psychological support for patients as well as parents, and follow-up is necessary for the early detection of malignant transformation. Detailed knowledge of this very rare condition may enable us to develop newer treatment modalities to achieve better outcomes in the near future.

The value of regular follow‐up of oral leukoplakia for early detection of malignant transformation

AbstractObjectivesEvaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT).MethodTwo hundred and twenty‐two consecutive patients with OL (147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up.ResultsOLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022).ConclusionRegular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible.

Utility of comet assay of DNA damage in the detection of malignant transformation of chronic liver cirrhosis

Early detection of hepatocellular carcinoma (HCC) remains a great challenge in laboratory medicine. This study aimed to assess the ability to use the degree of DNA damage (using the comet assay) for the early detection of malignant transformation of liver cirrhosis (LC) to HCC. We used alkaline comet assay for measuring DNA damage in peripheral blood lymphocytes in 50 patients with chronic LC and 50 patients with HCC. Fifty healthy individuals served as a control group. We compared the results of comet assay parameters with alpha fetoprotein as a relevant traditional marker. The HCC group was associated with a significantly higher tail intensity (p=.004), tail moment (p=.016), total area (p=.003), total intensity (p=.010), width (p=.005), and a significantly lower head intensity (.004) when compared to the LC group. Good areas under the curve (AUCs) were found for total area (0.890), head intensity (0.880) and tail intensity (0.880), making it useful for discrimination between HCC and LC groups. Lower head intensity, higher tail intensity, tail moment, total area and width were found to be independent risk factors for HCC on top of LC. Measuring DNA damage using the Alkaline comet assay technique can be considered a sensitive and reliable diagnostic tool for early neoplastic transformation of advanced LC.

HPV typing as the method of choice in the prevention and early detection of cervical cancer

Background: Human papillomavirus (HPV) is recognized as the primary cause of cervical cancer (CC), and significant coexisting factors have also been identified. CC is considered a curable disease because it has a long preinvasive period. It is possible to organize effective screening, and the treatment of preinvasive lesions is successful. Aim: To show the importance of HPV typing in the early detection of premalignant cervical disease. Method: Literature review, synthesis, and extraction of key professional and contemporary literature. Results: Depending on the methods used in identification, the presence of different types of HPV was identified in about 90% of intraepithelial neoplasia and CC samples. HPV genotyping plays an important role in the detection of dysplasia and helps to reduce the number of false-positive Pap test results. Randomized controlled trials have shown that CC screening with HPV testing offers greater protection against cervical precancer and cancer compared with cytology-based screening. To date, it has been proven that HPV 16 and 18 genotypes have the highest oncogenic potential. These two genotypes are responsible for about 70% of all squamous cell carcinomas, 30-40% of vulvar cancers, and about 85% of cervical adenocarcinomas. According to a recent report, 48 (35%) of 139 countries recommended HPV-based cervical screening, with most currently switching from cytology to HPV testing. Conclusion: HPV typing can be of great benefit in the early detection of malignant transformation of infected cells and the prevention of CC.

Oral Squamous Cell Carcinoma arising from Lichenoid Contact Reaction: A Case Report

Lichenoid contact reaction is a type of delayed hypersensitivity reaction to constituents derived from dental materials. It may occasionally transform into oral squamous cell carcinoma. A 62-year-male reported with the chief complaint of a wound in the inner aspect of right cheek for 2 weeks. On initial examination, a diffuse erythematous area with interspersed non- scrapable white striae was present on the right buccal mucosa and residual alveolar ridge with respect to 47 extending till gingivobuccal aspect of 45, roughly linear in shape, approximately 3x1 cm2 in size, with a rough overlying surface. Ointment triamcinolone 0.1% was prescribed for 1 week. The patient visited after 3 months. Clinical examination revealed an ulcer with peripheral induration of size approximately 2.5 mm on right buccal mucosa adjacent to 46. An incisional biopsy revealed oral squamous cell carcinoma. Long-term follow-up of patients with oral lichenoid reaction is mandatory for early detection of malignant transformation.

Immunohistochemical expression of FAP and PCNA in neoplastic epithelial colonic lesions

Background Colorectal carcinoma is one of the leading causes of morbidity and mortality worldwide. Fibroblast-activation protein is expressed in cancer-associated fibroblasts and its expression is upregulated during the transformation of benign colorectal tissue into cancer. Proliferating-cell nuclear antigen expression was used as a marker of cell proliferation and is considered as a marker able to identify aggressive adenomas that may in turn become malignant. Aim To study the expression of fibroblast-activation protein and proliferating-cell nuclear antigen in neoplastic epithelial colonic lesions and their role in adenoma–carcinoma sequence. Patients and methods This retrospective study aimed to evaluate the expression of fibroblast-activation protein and proliferating-cell nuclear antigen in 80 cases of neoplastic epithelial colonic lesions. Results In malignant colorectal epithelial tumors, high fibroblast-activation protein expression was detected with an increase in histological grade, depth of invasion, vascular invasion, and lymph-node metastasis. No fibroblast-activation protein expression was detected in all benign cases. In included benign cases, there was a significant relation between proliferating-cell nuclear antigen labeling index and both histological type and grade of dysplasia. In the included malignant cases, there was a significant relation between proliferating-cell nuclear antigen labeling index with grade of tumor and the depth of invasion. Conclusions Both fibroblast-activation protein and proliferating-cell nuclear antigen labeling index suggested to have a role in early detection of malignant transformation and had a prognostic role in malignant cases.

Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients

BackgroundOral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear.MethodsWe designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded.ResultsThe study population included 123 men and 442 women aged 21–93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type.ConclusionsOur results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

Accelerated aging in normal breast tissue of women with breast cancer

BackgroundDNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean.MethodsWe generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation.ResultsWe found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer.ConclusionsA subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

Management of oral leukoplakia: a position paper of the Society of Oral Medicine, Chinese Stomatological Association

The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

Analysis of downregulated salivary proteins in oral submucous fibrosis – A quantitative proteomic pilot study

Background: Oral submucous fibrosis (OSMF) is a chronic debilitating disease of the oral cavity which is strongly associated with chewing of areca nut. The rate of malignant transformation varies between 3% and 19%. As oral lesions are in direct contact with saliva, the altered composition of saliva has shown promising results in surveillance of malignant transformation. Aim: To do quantitative proteomic profiling of saliva in OSMF and to study the downregulated proteins. Methodology: Quantitative proteomic profiling was carried out using Liquid chromatography with Tandem mass spectroscopy (LC–MS/MS) on saliva obtained from patients with OSMF. Results: A total of 172 proteins were identified in saliva samples. Five proteins were downregulated in the samples (fold change average of disease vs. control ratio ≤0.6). Conclusion: Downregulated proteins could serve as potential biomarkers in the early detection of malignant transformation in OSMF.

Expression of p63 and Proliferating Cell Nuclear Antigen in Oral Submucous Fibrosis.

ABSTRACTAim:Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as oral submucous fibrosis (OSMF). p63 can detect genetic changes in OSMF and it facilitates early detection of malignant transformation, whereas proliferating cell nuclear antigen (PCNA) is a marker of proliferation and may prove to be a useful objective indicator of the biological behavior of various tumors. The aim of this study was to investigate the expression and pattern of the intensity of p63 protein and PCNA in normal oral mucosa and OSMF using immunohistochemistry (IHC) and to correlate the expression of these biomarkers.Materials and Methods:A total of 15 archival paraffin-embedded blocks obtained from our department, which were histopathologically diagnosed early OSMF (n = 4), intermediate OSMF (n = 4), and advanced OSMF (n = 2) and normal mucosa (n = 5), were taken as the standard for comparison. p63 and PCNA positivity was analyzed using Kruskall-Wallis test followed by pairwise comparison using Mann-Whitney U test. The pattern of staining and intensity was compared using Chi-Square test for which Statistical Package for the Social Sciences (SPSS, v 22.0, IBM Corporation, Armonk, New York) was used.Results:All samples showed positive staining for p63 and PCNA. A statistically significant difference (P < 0.05) was seen between the frequency of occurrence of p63 and the PCNA pattern of expression among all the groups. The intensity of staining was mild to intense in the basal layer, as there was a progression toward the severity of the disease. Almost 75.4% correlation existed between p63 and PCNA, with high correlation and marked relationship.Conclusions:The OSMF is considered a potentially malignant disorder that has the potential to get transformed into OSCC. The malignant transformation is often associated with changes at the genetic level, and these are reflected by the altered expression of proteins. Our results showed that biomarkers such as p63 and PCNA are significant in predicting the malignant transformation in OSMF, so in future they may serve as a prognostic tool in the early detection of malignancies.

Gaint Condylomata Acuminate of Buschke-Lowenstein in Woman with HPV Infection: Clinical Presentation and Treatment

Buschke-Lowenstein Tumor (BLT) is a very rare sexually- transmitted disease associated with human papillomavirus type 6 and 11, but rare cases of oncogenic HPV types including HPV 16 and HPV 18 were also reported. BLT is located in the genital, anorectal and perianal regions. It is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces where it is locally invasive but displays a benign cytology. Buschke-Lowenstein tumor can be associated with a high rate of recurrence and a risk of malignant transformation to invasive SCC, especially in patients with oncogenic types of HPV. We report the case of a 59-year-old female patient who addressed our clinic for a large, exophytic, cauliflower-like tumor involving the vulva, perineum and perianal regions with 20 years duration. The first lesions had been appeared on vulva and after 3 years period they grown slowly and covered perineum and perianal area. They had cauliflower like surface, with different sizes. In some points erosions and yellowish secretion with odor are observed. Histologic examination of a biopsy specimen of large tumor presented nets of well- differentiated squamous cell carcinoma, as well as a marked mononuclear cell infiltrate and conspicuous koilocytosis. HPV DNA for 6 and 11 types was detected with PCR. The patient was sent to the gynecology surgery department for excision and remains under the supervision of the dermatology and oncology department for rapid treatment of relapses and early detection of malignant transformation.

GRINSPAN SYNDROME: THE TRIAD

Lichen Planus is a chronic immunologically mediated mucocutaneous disorder with varied clinical manifestations. The condition might be associated with multiple causative or exacerbation factors. An interesting association of Oral Lichen Planus with Diabetes Mellitus and vascular hypertension is called as Grinspan's syndrome. Since its inception has been an arena of interest. It has appeared very lucrative to many researchers as it lacks clarity and enhanced ambiguity. A 65 year female patient came with a complaint of burning mouth and difficulty in swallowing since 1 year with H/O Diabetes Mellitus since 8years and hypertension since 2 years. Malignant transformation is the most significant complication of long standing and non healing Lichen Planus. Repeated follow up and biopsies are mandatory for prevention and early detection of malignant transformation.&#x0D; Keywords: Grinspan Syndrome, Hypertrophic Lichen Planus, Esophageal Lichen Planus

Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are rare aggressive sarcomas with poor prognosis. More than half of MPNSTs develop from benign precursor tumors associated with neurofibromatosis type 1 (NF1) which is a tumor suppressor gene disorder. Early detection of malignant transformation in NF1 patients is pivotal to improving survival. The primary aim of this study was to evaluate the role of immuno-modulators as candidate biomarkers of malignant transformation in NF1 patients with plexiform neurofibromas as well as predictors of response to immunotherapeutic approaches.MethodsSera from a total of 125 NF1 patients with quantified internal tumor load were included, and 25 of them had MPNSTs. A total of six immuno-modulatory factors (IGFBP-1, PD-L1, IFN-α, GM-CSF, PGE-2, and AXL) were measured in these sera using respective ELISA.ResultsNF1 patients with MPNSTs had significantly elevated PD-L1 levels in their sera compared to NF1 patients without MPNSTs. By contrast, AXL concentrations were significantly lower in sera of NF1-MPNST patients. IGFBP-1 and PGE2 serum levels did not differ between the two patient groups. IFN-α and GM-CSF were below the detectable level in most samples.ConclusionThe immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches.

Analysis of octamer-binding transcription factor-4 expression in oral leukoplakia.

Background:Oral potentially malignant disorders have a risk for malignant transformation but are difficult to reliably identify and predict which patients are at the risk for malignant transformation. OCT4 has been hypothesized to play a key oncogenic driver in a variety of solid tumors. A deeper understanding of the aberrant molecular pathways which lead to carcinogenesis needs to be identified by the potential markers.Aims:To assess the OCT4 stemness factor in oral leukoplakia for its potential risk to malignant transformation.Settings and Design:20 cases of oral leukoplakia were obtained from archives at Oral Cancer Research & Coordinating center (OCRCC) Malaysia Subjects and Methods: 20 cases of oral leukoplakia were assessed by OCT4 immunohistochemically. Oral squamous cell carcinoma was used as a control.Result:no expression of OCT 4 was observed in any cases of oral leukoplakia.Conclusion:The molecular mechanisms of Oct4 regulation and in particular of its switch on and off in tissues depends upon its microenvironment, which makes it challenging in fundamental and applied research fields of regenerative medicine and cancer therapy. It's better that patients should undergo multiple biopsies for the early detection of malignant transformation with close follow-up during the first two to three years, a large amount of work remains to be done with multi-marker panel investigation, as cure rates have remained constant over three decades.

Personalizing Gastric Cancer Screening With Predictive Modeling of Disease Progression Biomarkers.

Gastric cancer (GC) remains the third most common cause of cancer-related death worldwide. Infection with Helicobacter pylori is responsible for over 70% of GC incidence; colonization induces chronic inflammation, which can facilitate progression to intestinal metaplasia, dysplasia, and GC (Correa pathway). Although H. pylori eradication is a necessary first step in GC prevention, some patients continue to progress to advanced stage disease if substantial tissue damage has occurred or inflammation persists. This progression is often asymptomatic until cancer reaches stage IV, yet efficient, cost-effective screening protocols for patients who present with early stages of the Correa pathway do not exist. Given the high interpatient heterogeneity in progression time through this pathway, such screening protocols must necessarily be personalized. This requires the identification of reliable and longitudinally assessable biomarkers of patient-specific progression. Several gastric stem cell (GSC) markers including CD44, CD133, and Lgr5 are upregulated in GC. Here we show a significant stepwise increase in immunohistochemical staining for these markers in biopsies at different stages of the Correa pathway, suggesting GSC fraction to be a promising candidate biomarker for early detection of malignant transformation. We present a mathematical model capable of both simulating clinically observed increases in GSC fraction in longitudinal biopsy samples of individual patients, and forecasting patient-specific disease progression trajectories based only on characteristics identified from immunohistochemistry at initial presentation. From these forecasts, personalized screening schedules may be identified that would allow early stratification of high-risk patients, and potentially earlier detection of dysplasia or early-stage GC.

Serum fucose level in oral cancer, leukoplakia, and oral sub mucous fibrosis: A biochemical study.

Aims:To estimate the serum fucose levels in clinically and histopathologically diagnosed oral cancer, oral leukoplakia, and oral submucous fibrosis cases. To compare and correlate the severity of dysplasia or histopathological grading of the premalignant and malignant lesions with serum fucose levels.Objective:To determine the role of serum fucose as a reliable biomarker for early detection of malignant transformation of potentially malignant lesions and conditions and prediction of biologic behavior of the malignant lesions.Material and Method:The intended study shall include 100 participants divided into 4 groups. Groups I, II, and III will include 25 clinically and histological diagnosed cases of oral leukoplakia, oral submucous fibrosis, and oral cancer, and 25 normal control group. Fucose was measured according to the method of Dische and Shettles as adopted by Winzler.Statistical Analysis:Statistical analysis will be done using SPSS statistical software (Version 10), and the levels of significance will be analyzed using the paired and unpaired t-tests.Result:In subjects of 4 groups were age- and gender-matched and comparable thus these may also not influence the study outcome measure (fucose levels). ANOVA revealed significantly different fucose levels among the groups (F = 17.00, P < 0.001). Mean fucose level did not differ (P > 0.05) between oral leukoplakia, oral submucous fibrosis, and oral cancer (84.5%) groups. The increase in mean fucose levels with severity was the highest in the oral cancer group followed by oral submucous fibrosis and oral leukoplakia group. The mean fucose levels did not differ between mild and moderate grades (P > 0.05) in all the 3 groups.Conclusion:The evaluation of serum l-fucose would be of good help in assessing early malignant change in increasing the accuracy of clinical diagnosis and also in assessing the spread and invasiveness of oral cancer, oral submucous fibrosis, and leukoplakia.

Clinicopathologic characteristics of ovarian clear cell carcinoma in the background of endometrioma: a surveillance strategy for an early detection of malignant transformation in patients with asymptomatic endometrioma.

ObjectiveThis study aimed to analyze the clinical features of clear cell carcinoma in relation to endometriosis and to determine an appropriate surveillance strategy for the early detection of malignant transformation of endometrioma in asymptomatic patients.MethodsWe retrospectively reviewed the clinicopathologic data of 50 patients with ovarian clear cell carcinoma. Clinicopathologic characteristics, treatment outcomes, and the association between endometriosis and the risk of malignant transformation were analyzed.ResultsTen (20%) patients had been diagnosed with endometrioma before the diagnosis of clear cell carcinoma. The median period from the diagnosis of endometrioma to clear cell carcinoma diagnosis was 50 months (range, 12–213 months). After complete staging surgery, histological confirmation of endometriosis was possible in 35 (70%) patients. Of the 50 patients, 39 (78%) had not undergone any gynecologic surveillance until the onset of symptoms, at which time many of them presented with a rapidly growing pelvic mass (median 10 cm, range 4.6–25 cm). With the exception of 2 patients, all cancer diagnoses were made when the patients were in their late thirties, and median tumor size was found to increase along with age. Asymptomatic patients (n=11) who had regular gynecologic examinations were found to have a relatively smaller tumor size, lesser extent of tumor spread, and lower recurrence rate (P=0.011, 0.283, and 0.064, respectively). The presence of endometriosis was not related to the prognosis.ConclusionConsidering the duration of malignant transformation and the timing of cancer diagnosis, active surveillance might be considered from the age of the mid-thirties, with at least a 1-year interval, in patients with asymptomatic endometrioma.

A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.

Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.