Clinical characteristics of early-onset gastric cancer. A study in a Colombian population.

Gastric cancer is a multifactorial disease with important genetic and environmental factors. It is the fifth most common cancer in incidence, and the fourth cause of death secondary to cancer. The incidence of early-onset gastric cancer is increasing worldwide, but clinical information on these patients has not been well established. We analyzed the association between age and clinical, endoscopic, and histopathological characteristics of gastric cancer at the time of diagnosis in a Latin American population. A retrospective and descriptive cross-sectional study was carried out using the database of the Gastroenterology Service of the Clínica Foscal and Clínica Foscal Internacional in Bucaramanga, Colombia. Between January 2016 and December 2019, 259 de novo gastric cancer cases were diagnosed, of which 36 patients (13.9%) were 40 years old or younger. In patients with early-onset gastric, the prevalence of gastric cancer diagnosis was lower in men. A family history of gastric cancer or any other neoplasm was not associated with a higher prevalence of gastric neoplasms. In young patients, vomiting and ascites were more common, the preferred anatomical location was the body of the stomach, and the Borrmann IV classification and the diffuse-type histology were more likely. Our study showed an approximation of the characteristics of early-onset gastric cancer in a Latin American population, where we observed that early-onset gastric cancer has different demographic, anatomical, and histological features than late-onset gastric cancer.

Systematic Review of Microthrombi in COVID-19 Autopsies.

BACKGROUND: Histopathological analysis can provide additional clues in COVID-19 understanding. During the last year, autopsy reports have revealed that diffuse alveolar damage (DAD) is the most significant observed finding. The aim of this study is to review cases in the literature about COVID-19 autopsies that reported microthrombi in different organs. METHODS: We performed a systematic literature review in PubMed, Virtual Health Library (VHL), and Google Scholar. RESULTS: In total, 151 autopsies were included, and 91 cases presented microthrombi in the lung (73%), heart (11.2%), kidney (24%), and liver (16.3%). The age range was between 27 and 96 years. Males were 64.8%. The patients with microthrombi had more comorbidities such as arterial hypertension (62%), obesity or overweight (64%), diabetes mellitus type 2 (51%), and heart disease (53%). The most common histopathological changes found in patients with lung microthrombosis were DAD in exudative phase (78%), pulmonary embolism (59%), and lung infarct (81%). Presence of microthrombi was associated with arterial hypertension (p < 0.0001) and DAD in exudative and proliferative phases (p = 0.02). DISCUSSION: The analysis of these results shows that microthrombi in COVID-19 autopsies may be found in different organs and are more frequent in patients with comorbidities, pulmonary embolism, and lung infarct.

Pathogenesis of Penile Squamous Cell Carcinoma: Molecular Update and Systematic Review.

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.

How Wide Should the Excision Margins for Facial Small Aggressive Basal Cell Carcinoma Be? Experience With 306 Cases.

BACKGROUND: Subclinical extension (SCE) of basal cell carcinomas (BCCs) may be responsible for incomplete resection of the tumor. The aggressive histological patterns (micronodular, infiltrative, and morpheaform) have greater tendencies toward invading surrounding tissues in an irregular pattern. OBJECTIVE: To determine the SCE of small facial aggressive BCCs excised using Mohs micrographic surgery (MMS). MATERIALS AND METHODS: An observational case series study. Data of patients with facial BCCs with aggressive histological patterns, less than or equal to 6 mm in diameter in high risk site (H zone), and 10 mm in intermediate risk site (M zone), treated with MMS between January 2008 and December 2016, were included. RESULTS: This study included 306 histologically confirmed lesions retrieved from 1,196 clinical records reviewed. Median size of tumors was 5.7 mm (interquartile range: 5-6 mm). Resection of the tumors using 2, 3, and 4 mm margins achieves complete excision of the lesion including the subclinical extension area in 73.9%, 94.4%, and 99% of cases, respectively. CONCLUSION: The present study demonstrated that a 4-mm resection margin was enough to eradicate the lesion completely in 99% of cases of primary small facial BCCs with aggressive histological patterns.

A Systematic review and Meta-Analysis of the survival and clinicopathological features of p63 expression in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare skin tumour of neuroendocrine origin with aggressive behaviour. The aims of this study were to investigate the association of p63 + MCC with clinicopathological features and to estimate survival through a systematic review and meta-analysis. A comprehensive search of PubMed, Embase, Scopus and Virtual Health Library following the PRISMA guidelines was conducted on September 2017. DerSimonian and Lard random-effects models were used to calculate survival-weighted means and their corresponding 95% confidence intervals (CI) among studies. Five studies met our inclusion criteria after screening 77 citations and 36 full-text articles. The included studies enrolled 413 patients with MCC. We observed that p63 + MCC was significantly associated with mortality with OR 2.92 (95% CI [1.66-5.13]). The summary hazard ratio of multivariate analysis was 1.99 (95% CI [1.32-3.01]). The only clinicopathological feature associated with p63 + MCC with statistical significance was the Merkel cell polyomavirus (MCPyV) status. The presence of MCPyV was associated as a protective factor for the expression of p63 (OR 0.25, 95% CI [0.08-0.73]). These results support that p63 + MCC evaluated by immunohistochemistry has a poor outcome. Therefore, we suggest p63 to be performed when staging MCC.

Metastatic Malignant Pilomatrixoma in an 8-Year-Old Girl Misdiagnosed as a Recurrent Pilomatrixoma.

Malignant pilomatrixoma or pilomatrix carcinoma is a rare, locally aggressive malignant neoplasm, derived from the hair follicle with a high propensity for local recurrence. Only a few cases of metastatic pilomatrixoma have been described in the literature. Till date, only 17 cases have been reported in the English-language medical literature, most commonly occurring associated with local recurrence in adults. We report the first case in children of a metastatic malignant pilomatrixoma in an 8-year-old girl presenting with a recurrent pilomatrix carcinoma of the forehead with metastases in cervical and parotid lymph nodes.

Diagnostic utility of epithelial and melanocitic markers with double sequential immunohistochemical staining in differentiating melanoma in situ from invasive melanoma.

Identification of melanoma in situ and its distinction from invasive melanoma is important because of its significant impact on morbidity and mortality. However, this interpretation can cause pitfalls in the diagnosis even with the use of immunohistochemistry. The aim of this study is to evaluate the diagnostic utility of epithelial makers (AE1/AE3, CK5/6, and p63) combined with melanocytic markers (HMB-45, S-100, or Melan-A) using dual-color immunohistochemical staining, performed on a single slide by sequentially applying the antibodies. In this study, we show 4 cases in which examination of routine hematoxylin and eosin slides did not allow for clear-cut distinction between in situ and invasive melanoma and highlight the utility of the double-staining method. Therefore, we recommend this double-staining method with melanocytic and epithelial markers as a helpful adjunct to the diagnosis of cases with a differential diagnosis between in situ and invasive melanoma.

Cutaneous Collision Tumor Associated With Porocarcinomatous and Angiosarcomatous Components: A Potential Diagnostic Pitfall.

Sarcomatoid eccrine porocarcinoma (SEP) is a very rare malignancy including epithelial and mesenchymal components exhibiting pleomorphic cells, nuclear hyperchromasia, and high mitotic activity in both elements. To date, only 6 cases of this uncommon neoplasm have been reported, corresponding to women over 70 years of age with ulcerated skin lesions. The authors describe the first sarcomatoid eccrine porocarcinoma in a 75-year-old male patient with a right hallux lesion, presenting a collision tumor with a mixed population of epithelial cells and a spindle cell angiosarcomatous mesenchymal component each expressing distinct and nonoverlapping morphologic and immunohistochemical features of epithelial and mesenchymal differentiation.

Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

BACKGROUND: Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. METHODS: The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. RESULTS: 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. CONCLUSION: Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

Crossing the Andes: Challenges and opportunities for digital pathology in Latin America.

The most widely accepted and used type of digital pathology (DP) is whole-slide imaging (WSI). The USFDA granted two WSI system approvals for primary diagnosis, the first in 2017. In Latin America, DP has the potential to reshape healthcare by enhancing diagnostic capabilities through artificial intelligence (AI) and standardizing pathology reports. Yet, we must tackle regulatory hurdles, training, resource availability, and unique challenges to the region. Collectively addressing these hurdles can enable the region to harness DP's advantages-enhancing disease diagnosis, medical research, and healthcare accessibility for its population. Americas Health Foundation assembled a panel of Latin American pathologists who are experts in DP to assess the hurdles to implementing it into pathologists' workflows in the region and provide recommendations for overcoming them. Some key steps recommended include creating a Latin American Society of Digital Pathology to provide continuing education, developing AI models trained on the Latin American population, establishing national regulatory frameworks for protecting the data, and standardizing formats for DP images to ensure that pathologists can collaborate and validate specimens across the various DP platforms.

Globalization of a telepathology network with artificial intelligence applications in Colombia: The GLORIA program study protocol.

In Colombia, cancer is recognized as a high-cost pathology by the national government and the Colombian High-Cost Disease Fund. As of 2020, the situation is most critical for adult cancer patients, particularly those under public healthcare and residing in remote regions of the country. The highest lag time for a diagnosis was observed for cervical cancer (79.13 days), followed by prostate (77.30 days), and breast cancer (70.25 days). Timely and accurate histopathological reporting plays a vital role in the diagnosis of cancer. In recent years, digital pathology has been globally implemented as a technological tool in two main areas: telepathology (TP) and computational pathology. TP has been shown to improve rapid and timely diagnosis in anatomic pathology by facilitating interaction between general laboratories and specialized pathologists worldwide through information and telecommunication technologies. Computational pathology provides diagnostic and prognostic assistance based on histopathological patterns, molecular, and clinical information, aiding pathologists in making more accurate diagnoses. We present the study protocol of the GLORIA digital pathology network, a pioneering initiative, and national grant-approved program aiming to design and pilot a Colombian digital pathology transformation focused on TP and computational pathology, in response to the general needs of pathology laboratories for diagnosing complex malignant tumors. The study protocol describes the design of a TP network to expand oncopathology services across all Colombian regions. It also describes an artificial intelligence proposal for lung cancer, one of Colombia's most prevalent cancers, and a freely accessible national histopathological image database to facilitate image analysis studies.

Construction of an immune gene expression meta signature to assess the prognostic risk of colorectal cancer patients.

Despite recent advancements in colorectal cancer (CRC) treatment, particularly with the introduction of immunotherapy and checkpoint inhibitors, the efficacy of these therapies remains limited to a subset of patients. To address this challenge, our study aimed to develop a prognostic biomarker based on immune-related genes to predict better outcomes in CRC patients and aid in treatment decision-making. We comprehensively analysed immune gene expression signatures associated with CRC prognosis to construct an immune meta-signature with prognostic potential. Utilising data from The Cancer Genome Atlas (TCGA), we employed Cox regression to identify immune-related genes with prognostic significance from multiple studies. Subsequently, we compared the expression levels of immune genes, levels of immune cell infiltration, and various immune-related molecules between high-risk and low-risk patient groups. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses provided insights into the biological pathways associated with the identified prognostic genes. Finally, we validated our findings using a separate CRC cohort from the Gene Expression Omnibus (GEO). Integration of the prognostic genes revealed significant disparities in survival outcomes. Differential expression analysis identified a set of immune-associated genes, which were further refined using LASSO penalisation and Cox regression. Univariate Cox regression analyses confirmed the autonomy of the gene signature as a prognostic indicator for CRC patient survival. Our risk prediction model effectively stratified CRC patients based on their prognosis, with the high-risk group showing enrichment in pro-oncogenic terms and pathways. Immune infiltration analysis revealed an augmented presence of certain immunosuppressive subsets in the high-risk group. Finally, we validated the performance of our prognostic model by applying the risk score equation to a different CRC patient dataset, confirming its prognostic potential in this new cohort. Overall, our study presents a novel immune-related gene signature with promising implications for predicting cancer progression and prognosis, thereby enabling more personalised management strategies for CRC patients.

PD-L1 expression in non-small cell lung carcinoma in Latin America: a systematic review and meta-analysis.

Background: Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is a crucial factor in predicting responses to immunotherapy. This systematic review and meta-analysis focuses on the prevalence of PD-L1 expression and clinicopathological features among Hispanic/Latino (H/L) populations. Methods: Embase, LILACS, Medline, and Virtual Health Library were searched for studies that evaluated the prevalence of PD-L1 in H/L patients. The protocol was submitted to PROSPERO with ID CRD42023488547. We employed the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses to assess the methodological quality and applicability of the included studies. Meta-analyses were done to determine the prevalence using a random effects model. Results: The meta-analysis, encompassing 21 articles with 16,486, revealed that 80.2% of patients had PD-L1 expression data available (n=13,222). The prevalence calculated of PD-L1 expression in Latino NSCLC patients was 55% [95% confidence interval (CI): 0.54-0.55], with 31% (95% CI: 0.27-0.36) showing a tumoral proportion score (TPS) of 1-49%, and 23% (95% CI: 0.16-0.30) registering a TPS ≥50%. Higher expression was observed in male gender, smoking, adenocarcinoma subtypes, poor tumor differentiation, and advanced stages. PD-L1 expression was most frequent in EGFR wild-type status (82.5%) with a odds ratio (OR) 1.54 (95% CI: 1.24-1.92) and PD-L1 expression was associated with ALK positive (OR =1.54; 95% CI: 1.24-1.92). Conclusions: This meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC in the H/L population. The findings underscore the significant prevalence of PD-L1 expression and emphasize the relevance of immunotherapy in this population. Understanding the clinicopathological features associated with PD-L1 expression can contribute to tailored treatment strategies for NSCLC in Latin America.

Cellular Senescence in Diffuse Gliomas: From Physiopathology to Possible Treatments.

Cellular senescence in gliomas is a complex process that is induced by aging and replication, ionizing radiation, oncogenic stress, and the use of temozolomide. However, the escape routes that gliomas must evade senescence and achieve cellular immortality are much more complex, in which the expression of telomerase and the alternative lengthening of telomeres, as well as the mutation of some proto-oncogenes or tumor suppressor genes, are involved. In gliomas, these molecular mechanisms related to cellular senescence can have a tumor-suppressing or promoting effect and are directly involved in tumor recurrence and progression. From these cellular mechanisms related to cellular senescence, it is possible to generate targeted senostatic and senolytic therapies that improve the response to currently available treatments and improve survival rates. This review aims to summarize the mechanisms of induction and evasion of cellular senescence in gliomas, as well as review possible treatments with therapies targeting pathways related to cellular senescence.

The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives.

Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.

Colombian consensus for the molecular diagnosis of endometrial cancer / Consenso colombiano para el diagnóstico molecular del cáncer de endometrio.

Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and nonregulatory document.

Objetivos: el programa Cancer Genome Atlas Research (TCGA) desarrolló la clasificación molecular para cáncer endometrial con utilidad pronóstica y terapéutica, la cual ha sido reemplazada por consensos y guías internacionales por la clasificación ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) debido a su alto costo. El objetivo de este artículo es presentar recomendaciones a nivel nacional derivadas de un consenso de expertos que permitan unificar e implementar la clasificación molecular para mujeres con cáncer endometrial, mediante un uso racional de recursos y tecnología. Materiales y métodos: consenso de 36 expertos en oncología clínica, ginecología oncológica, patología y genética con práctica clínica en el territorio nacional. El grupo líder realizó una revisión de la literatura y estructuración de preguntas calificadas de 1 a 9 puntos. Se utilizó la técnica de grupo nominal modificada. Se efectuaron reuniones presenciales con presentaciones magistrales, diálogo deliberativo y votación de cuestionario Google Forms (Google LLC, Mountain View, CA, USA) con análisis y discusión de respuestas. Las respuestas no consensuadas se llevaron a una segunda ronda de votación. Finalmente, se elaboró y revisó el manuscrito final. Resultados: se formularon siete recomendaciones integrando las respuestas de las panelistas basadas en evidencia, pero ajustadas al contexto y a la realidad colombiana. Recomendación 1. Se recomienda realizar la clasificación molecular en todos los carcinomas endometriales utilizando los marcadores de inmunohistoquímica como resultados subrogados del perfil molecular inicialmente propuesto en la clasificación del TCGA. Recomendación 2. Se recomienda la estrategia secuencial de testeo iniciando por los marcadores de inmunohistoquímica (p53, MLH1, MSH 2, MSH6, PMS2) simultáneamente en todas las pacientes, y definir la solicitud del POLE (polimerasa épsilon del DNA) (si se encuentra disponible) de forma diferida de acuerdo con la clasificación de riesgo basado en la pieza quirúrgica. Recomendación 3. Se recomienda que sea el ginecólogo oncólogo quien solicite el POLE (si se encuentra disponible) de acuerdo con el reporte de patología definitivo. Esta prueba se debe solicitar a todos los cánceres endometriales de estadio I-II, excepto los de bajo riesgo (estadio IA endometrioide de bajo grado sin invasión linfovascular p53 normal) y estadio III-IV sin enfermedad residual, sin afectar la solicitud de los marcadores moleculares subrogados por inmunohistoquímica de acuerdo con la histología. El consenso propone que la solicitud del POLE se realice posterior a la inmunohistoquímica y de acuerdo con la clasificación del riesgo según las categorías establecidas por la guía ESGO/ESTRO/ESP del 2020. Recomendación 4. Se recomienda realizar simultáneamente con los otros marcadores de inmunohistoquímica la prueba para receptores hormonales en todas las pacientes con cáncer endometrial y el HER2 en pacientes con p53abn. Recomendación 5. Se recomienda que los marcadores de inmunohistoquímica (p53, MLH1, MSH2, MSH6 y PMS2) se realicen en la biopsia/legrado endometrial inicial cuando la muestra es adecuada y está disponible. En caso de inmunohistoquímica inicial no concluyente, o discrepancias histológicas entre la patología inicial y definitiva, se recomienda repetir el perfil molecular en la patología quirúrgica. Los marcadores de inmunohistoquímica deben reportarse en el informe de patología de acuerdo con las recomendaciones del CAP (College of American Pathologists), independientemente del tipo de muestra. Recomendación 6. Se recomienda realizar estudio de metilación de promotor de MLH1 en pacientes con pérdida de expresión de MLH1 en la inmunohistoquímica, acompañado o no de pérdida de expresión de PMS2. Todas las pacientes con déficit de MMR (mismatch repair), deben ser enviadas a genética para descartar síndrome de Lynch. Recomendación 7. Se recomienda tener en cuenta la clasificación molecular, además de los criterios histopatológicos clásicos para la toma de decisiones de adyuvancia, tal como los incorpora la clasificación de los grupos pronósticos de la guía ESGO/ ESTRO/ESP del 2020. Conclusiones: es necesario implementar la clasificación molecular de cáncer de endometrio en la práctica clínica acorde al contexto colombiano, dado su valor pronóstico y posiblemente predictivo. Esto permitirá la caracterización de la población colombiana para ofrecer tratamientos guiados de manera individualizada. Se trata de un documento académico y no regulatorio.

Early Metastasis of Clear Cell Renal Cell Carcinoma to the Esophagus: A Case Report.

Metastatic involvement of clear cell renal cancer in the esophagus has been described in the literature as an uncommon condition. These usually present as late relapse causing clinical manifestations such as dysphagia and melena. We present the case of a 57-year-old man with a history of renal cell carcinoma who presented an early metastasis to the esophagus. In addition, we made a comparison of the reason for examination, time of relapse, and metastasis in other anatomical places of all the cases reported in the literature of esophageal involvement due to clear cell metastasis.

Prevalence of oncogenic driver mutations in Hispanics/Latin patients with lung cancer. A systematic review and meta-analysis.

INTRODUCTION: The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC. METHODS: EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients. Meta-analyses were done to determine prevalence using a random effects model. RESULTS: Fifty-five articles were included. EGFR and KRAS were the most prevalent genes with high heterogeneity across the countries. The overall mutation frequency for EGFR was 22%. The most frequent mutations in the EGFR gene were del19 (10%) and L858R (7%). The mean of KRAS mutation was a 14% prevalence. KRASG12C was the most frequent mutation with a 7% prevalence in an entire population. The overall frequency of ALK rearrangement was 5%. The mean frequency of ROS-1 rearrangement was 2%, and the frequencies of HER-2, MET, BRAF, RET, NTRK molecular alterations were 4%, 3%, 2%, 2%, and 1% respectively. Almost half of the cases were male, and 65.8% had a history of tobacco exposure. The most common clinical stage was IV. CONCLUSIONS: The prevalence of driver mutations such as EGFR and KRAS in LA populations differs from what is reported in Asians and Europeans. In the present article, countries with a high proportion of Amerindian ancestry show a greater prevalence of EGFR in contrast to countries with a high proportion of Caucasians. Lack of information on some countries or studies with a small sample size affects the real prevalence data for the region.

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a prevalent subtype of lung cancer associated with high mortality rates. We aimed to utilize single-cell multiomics analysis to identify the key molecules involved in ubiquitination modification, which plays a role in LUAD development and progression. Methods: We use a systematic approach to analyze LUAD-related single-cell and bulk transcriptome datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Single-cell RNA sequencing (scRNA-seq) data were normalized, clustered, and annotated with the Seurat package in R. InferCNV was used to distinguish malignant from epithelial cells, and AUCell evaluated the area under the curve (AUC) score of ubiquitination-related enzymes. Survival and differential analyses identified significant molecular markers associated with ubiquitination. PSMD14 expression was confirmed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assays, and its knockdown cell lines were assessed for effects on cellular processes and tumor formation in mice. PSMD14's interacting proteins were predicted, and its impact on AGR2 protein half-life and ubiquitination was evaluated. Rescue experiments involving PSMD14 overexpression and AGR2 silencing assessed their impact on malignant behaviors. Results: By means of single-cell sequencing analysis, we probed the ubiquitination modification landscape in the LUAD microenvironment. Malignant cells had elevated scores for enzymes and ubiquitin-binding domains compared to normal epithelial cells, with 53 ubiquitination-related molecules showing prognostic disparities. FGR, PSMD14, and ZBTB16 were identified as genes with prognostic significance, with PSMD14 showing higher expression in epithelial and malignant cells. Two missense mutation sites were identified in PSMD14, which had a high copy number amplification ratio and positive correlation with messenger RNA (mRNA) expression. PSMD14 expression and tumor stage were found to be independent prognostic factors, and interfering with PSMD14 expression reduced the malignant behavior of LUAD cells. PSMD14 was found to bind to AGR2 protein and reduce its ubiquitination, leading to increased AGR2 stability. Knockdown of AGR2 inhibited the enhancement of cell viability, invasion, and migration resulting from PSMD14 overexpression. Conclusions: This study examined ubiquitination modifications in LUAD using sequencing data, identifying PSMD14's critical role in malignancy regulation and its potential as a prognostic and therapeutic biomarker. These insights enhance understanding of LUAD mechanisms and treatment.