ATM phosphorylation of CD98HC increases antiporter membrane localization and prevents chronic toxic glutamate accumulation in Ataxia telangiectasia.

Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by neurological defects, immunodeficiency, cancer predisposition, radiosensitivity, decreased blood vessel integrity, and diabetes. ATM, the protein mutated in A-T, responds to DNA damage and oxidative stress, but its functional relationship to the progressive clinical manifestation of A-T is not understood. CD98HC chaperones cystine/glutamate (x c - ) and cationic/neutral amino acid (y + L) antiporters to the cell membrane, and CD98HC phosphorylation by ATM accelerates membrane localization to acutely increase amino acid transport. Loss of ATM impacts tissues reliant on SLC family antiporters relevant to A-T phenotypes, such as endothelial cells (telangiectasia) and pancreatic α-cells (fatty liver and diabetes) with toxic glutamate accumulation. Bypassing the antiporters restores intracellular metabolic balance both in ATM-deficient cells and mouse models. These findings provide new insight into the long-known benefits of N-acetyl cysteine to A-T cells beyond oxidative stress through removing excess glutamate by production of glutathione.

Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

Promoter hypermethylation of RARB and GSTP1 genes in plasma cell-free DNA as breast cancer biomarkers in Peruvian women.

BACKGROUND: Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case-control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach. METHODS: A total of 58 breast cancer patients and 58 healthy controls, matched by age, participated in the study. We exacted cell-free DNA (cfDNA) from blood plasma and converted it by bisulfite salts. Methylight PCR was performed to obtain the PMR value of the studied genes. We determined the association between PMR and breast cancer, in addition to other clinicopathological variables. The sensitivity and specificity of the PMR of these genes were obtained. RESULTS: A significant association was not found between breast cancer and the RARB PMR (OR = 1.90; 95% CI [0.62-6.18]; p = 0.210) or the GSTP1 PMR (OR = 6.57; 95% CI [0.75-307.66]; p = 0.114). The combination of the RARB + GSTP1 PMR was associated with breast cancer (OR = 2.81; 95% CI [1.02-8.22]; p = 0.026), controls under 50 years old (p = 0.048), patients older than 50 (p = 0.007), and postmenopausal (p = 0.034). The PMR of both genes showed a specificity of 86.21% and a sensitivity of 31.03%. CONCLUSION: Promoter hypermethylation of RARB + GSTP1 genes is associated with breast cancer, older age, and postmenopausal Peruvian patients. The methylated promoter of the RARB + GSTP1 genes needs further validation to be used as a biomarker for liquid biopsy and as a recommendation criterion for additional tests in asymptomatic women younger than 50 years.

A Spectrum of Metastases to the Breast: Radiologic-Pathologic Correlation.

Metastases to the breast from non-mammary origin are rare. The majority of these lesions appear as secondary manifestations of melanoma and lymphoma, followed by lung carcinomas, gynecological carcinomas, and sarcomas. There has been a steady trend of an increase in diagnosis of intramammary metastases owing to the current advances in imaging technology. Imaging features depend on the type of primary neoplasm and route of dissemination, some of which resemble primary breast cancer and benign breast entities. There are certain imaging features that raise the level of suspicion for metastases in the correct clinical context. However, imaging manifestations of intramammary metastases do not always comply with the known classic patterns. The aim of this review is to clarify these features, emphasizing radiologic-pathologic correlation and a multidisciplinary approach, since most cases are found in patients with advanced disease.

Chip-based digital Polymerase Chain Reaction as quantitative technique for the detection of PIK3CA mutations in breast cancer patients.

Background: PIK3CA is a gene frequently mutated in breast cancer. With the FDA approval of alpelisib, the evaluation of PIK3CA for activating mutations is becoming routinely. Novel platforms for gene analysis as digital PCR (dPCR) are emerging as a potential replacement for the traditional Sanger sequencing. However, there are still few studies on chip-based dPCR to detect mutations in tumor samples. Thus, this cross-sectional study aimed to assess the sensibility of a chip-based dPCR to detect and quantify PIK3CA mutations and compare its performance with Sanger sequencing. Materials and Methods: Tumor samples from 57 breast cancer patients (22 pre-treatment samples, 32 tumors after neoadjuvant chemotherapy, and three lymph nodes) were collected and analyzed by Sanger sequencing and dPCR for the three PIK3CA most relevant mutations (p.E545K, p. H1047R, and p. H1047L). Digital PCR sensitivity, specificity, and overall performance were estimated by contingency tables, receptor operator characteristic (ROC), and area under the curve (AUC). Association of PIK3CA mutations with clinicopathological variables was conducted. Results: Sanger sequencing identified PIK3CA mutations in six patients (10.5%), two with p. H1047R, and four with p. E545K. Digital PCR confirmed those mutations and identified 19 additional patients with at least one mutation. Comparison between dPCR and Sanger sequencing showed a sensitivity of 100% (95% CI 53-100%), and a specificity of 84.2% (95% CI 83-84.2%). Besides, p. H1047R mutation detected by dPCR showed a significant association with breast cancer phenotype (p = 0.019) and lymphatic nodes infiltration (p = 0.046). Conclusions: Digital PCR showed a high sensitivity to detect mutations in tumor samples and it might be capable to detect low-rate mutations and tumor subpopulations not detected by Sanger sequencing.

Development and characterization of a mass cytometry panel for detecting the effect of acute doxorubicin exposure on murine cardiac nonmyocytes.

Childhood cancer survivors (CCSs) face lifelong side effects related to their treatment with chemotherapy. Anthracycline agents, such as doxorubicin (DOX), are important in the treatment of childhood cancers but are associated with cardiotoxicity. Cardiac toxicities represent a significant source of chronic disability that cancer survivors face; despite this, the chronic cardiotoxicity phenotype and how it relates to acute toxicity remains poorly defined. To address this critical knowledge gap, we studied the acute effect of DOX on murine cardiac nonmyocytes in vivo. Determination of the acute cellular effects of DOX on nonmyocytes, a cell pool with finite replicative capacity, provides a basis for understanding the pathogenesis of the chronic heart disease that CCSs face. To investigate the acute cellular effects of DOX, we present single-cell RNA sequencing (scRNAseq) data from homeostatic cardiac nonmyocytes and compare it with preexisting datasets, as well as a novel CyTOF datasets. SCANPY, a python-based single-cell analysis, was used to assess the heterogeneity of cells detected in scRNAseq and CyTOF. To further assist in CyTOF data annotation, joint analyses of scRNAseq and CyTOF data using an artificial neural network known as sparse autoencoder for clustering, imputation, and embedding (SAUCIE) are performed. Lastly, the panel is tested on a mouse model of acute DOX exposure at two time points (24 and 72 h) after the last dose of doxorubicin and examined with joint clustering. In sum, we report the first ever CyTOF study of cardiac nonmyocytes and characterize the effect of acute DOX exposure with scRNAseq and CyTOF.NEW & NOTEWORTHY We describe the first mass cytometry studies of murine cardiac nonmyocytes. The mass cytometry panel is compared with single-cell RNA sequencing data. Homeostatic cardiac nonmyocytes are characterized by mass cytometry to identify and quantify four major cell populations: endothelial cells, fibroblasts, leukocytes, and pericytes. The single-cell acute nonmyocyte response to doxorubicin is studied at 24 and 72 h after doxorubicin exposure given daily for 5 days at a dose of 4 mg/kg/day.

Cost-Benefit Analysis of Robotic vs. Laparoscopic Hepatectomy: A Propensity-Matched Retrospective Cohort Study of American College of Surgeons National Surgical Quality Improvement Program Database.

BACKGROUND: Robotic and laparoscopic hepatectomies having increased utilization as minimally invasive techniques are explored for hepatobiliary malignancies. Although the data on outcomes from these 2 approaches are emerging, the cost-benefit analysis of these approaches remains sparse. This study compares the costs associated with robotic vs. laparoscopic liver resections, taking into account 30-day complications. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, a propensity-matched cohort of patients with laparoscopic or robotic liver resections between 2014 and 2017 was identified. Costs were assigned to perioperative variables, including operating room (OR) time, length of stay, blood transfusions, and 30-day complications. Cost estimates were obtained from the Centers for Medicare and Medicaid Services billing data (2017), American Hospital Association data (2017), relevant literature, and local institutional cost data. RESULTS: In our matched cohort of 454 patients (227 per group), total costs associated with laparoscopic liver resections were estimated at $5.5 M ($24 K per patient) vs. $6.8 M ($29.8 K per patient) for robotic liver resections (21.3% difference, P < .001). The higher cost associated with robotic hepatectomies was related to blood transfusions ($22.0 K vs. $12.1 K, P = .02), length of stay ($2.05 M vs. $1.76 M, P = .046), and OR time ($4.01 M vs. $3.24 M, P < .0001). DISCUSSION: Robotic hepatectomies were associated with higher costs compared to laparoscopic hepatectomies. The 2 major contributors to the cost disparity were increased OR time and increased length of stay. Future studies are warranted to analyze high-volume Minimally Invasive Surgery surgeons' impact in specialty centers on potentially mitigating this current cost disparity.

Highlights from the 7th Oncological Pathology Conference 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', 15, 22 and 23 July 2022, Trujillo, Peru.

The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public. The recent promulgation of the 'National Cancer Law' fosters the development of discussion forums to analyse the national realities and uphold continuous learning about experiences in other Latin American countries with successful cancer programmes, in which pathology holds a principal role. The topics addressed during this JoPaO included the exchange of Latin American cancer management experiences, an emphasis on investments in and the development of strategic plans to improve care, the use of new technologies, laboratory quality control, and the need to advance scientific research.

Effect of preoperative radiation on free flap outcomes for head and neck reconstruction: An updated systematic review and meta-analysis.

BACKGROUND: There is an ongoing debate about whether neoadjuvant radiation therapy is associated with higher rates of postoperative complications after head and neck reconstruction. Herle et al. conducted a systematic review in 2014 of 24 studies, finding higher complication rates in irradiated fields. We sought to perform an exhaustive updated systematic review and meta-analysis. METHODS: We conducted an updated systematic review of the literature, as outlined in our protocol, which was registered on PROSPERO. Databases included Medline, Embase, Cochrane Central, and Web of Science. There were no limits placed on the date range, place of publication, or origin. Exclusion criteria included patients less than 18 years of age, studies with less than 20 participants (n < 20), case studies, skull base reconstructions, and local tissue rearrangements. The combined results of the studies and relative risks (RR) were calculated. RESULTS: 53 studies were included for analysis, including 5,086 free flaps in an irradiated field, and 9,110 free flaps in a non-irradiated field. Of the 53 studies, 21 studies overlapped with those discussed in Herle et al.'s study, with a total of 32 additional studies. Neoadjuvant radiation was found to be a statistically significant risk factor for postoperative complications (RR 1.579, P < 0.001), total flap failure (RR, 1.565; P < 0.001), and fistula (RR, 1.810; P < 0.001). Our work reaffirmed the findings of the Herle et al. CONCLUSION: Preoperative radiation was associated with a statistically significant increase in the risk of total flap failure, fistula, and total complications but not partial flap failure. These high-morbidity complications must be taken into consideration when determining which patients should receive neoadjuvant radiation therapy.

Development of a Model for Abdominal Aortic Aneurysms in Swine.

INTRODUCTION: Producing a reliable large-animal model of AAA has proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. METHODS: Twelve male Yorkshire swine received periadventitial injections of type 1 collagenase and porcine pancreatic elastase into a 4 cm segment of infrarenal aorta. Nine survived until postoperative day (POD) 21. Aortic growth was monitored at 7 and 14 days using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal aorta were harvested for analysis, after gross measurement of aortic diameter (AD). Tensile strength was measured and additional segments were collected for histopathological analysis. PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA, where appropriate. RESULTS: Average percent growth of AD at POD 21 for treated segments was 27% versus 4.5% for control tissue. The average difference in AD by subject, was 26.7% (P<0.001). Aortic medial thickness was decreased in treated tissue; 235 µm versus 645 µm (P<0.0001). Quantities of both medial elastin fibers, and smooth muscles cells were decreased in treated tissue; 1.8% compared to 9.9% (P<0.0001), and 24% versus 37.4%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa versus 29.5 MPa (P=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (P=0.002) CONCLUSION: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.

Effect of Daily Dosage of Morphine Milligram Equivalents on Free Flap Complications: A Single-Institution Retrospective Study.

INTRODUCTION: There appears to be an association between preoperative opioid use and postoperative complications. We sought to determine whether patients with a history of chronic opiate use (defined as 3 months or more of sustained use) prior to undergoing free flap surgery have higher rates of 30-day complications. METHODS: A retrospective review of patients undergoing free flaps from 2015 to 2020 was performed. Patient characteristics were analyzed, including daily preoperative dose of opiates, which were then converted to morphine milligram equivalents; intra-operative variables such as estimated blood loss and operating room time; and 30-day outcomes, including wound and flap complications, return to the operating room, and readmissions. RESULTS: One hundred fifty-five patients received 160 free flaps. Of these flaps, 50/160 (31%) were performed on patients with an opiate prescription for at least three months prior to surgery. Using multivariable analysis, morphine milligram equivalents, a surrogate for opioid dose, were significantly associated with flap complications (odds ratio (OR) 1.011, 95% confidence interval (CI) 1.003-1.020, p<0.01), partial flap loss (OR 1.010, 95% CI 1.003-1.019, p<0.01), and surgical site infections (OR 1.017, 95% CI 1.007-1.027, p<0.01). Additionally, estimated blood loss was associated with partial flap loss (OR 4.838, 95% CI 1.589-14.728, p<0.006), and operating room time was also associated with flap complications (OR 1.337, 95% CI 1.152-1.150, p<0.01). CONCLUSION: Chronic preoperative opioid use is common for free flap surgery, and according to our single-center experience, higher daily doses are a risk factor for flap complications and surgical site infections. These findings add to the growing body of evidence that opioid use is a modifiable risk factor that may increase surgical morbidity.

Correlation AnalyzeR: functional predictions from gene co-expression correlations.

BACKGROUND: Co-expression correlations provide the ability to predict gene functionality within specific biological contexts, such as different tissue and disease conditions. However, current gene co-expression databases generally do not consider biological context. In addition, these tools often implement a limited range of unsophisticated analysis approaches, diminishing their utility for exploring gene functionality and gene relationships. Furthermore, they typically do not provide the summary visualizations necessary to communicate these results, posing a significant barrier to their utilization by biologists without computational skills. RESULTS: We present Correlation AnalyzeR, a user-friendly web interface for exploring co-expression correlations and predicting gene functions, gene-gene relationships, and gene set topology. Correlation AnalyzeR provides flexible access to its database of tissue and disease-specific (cancer vs normal) genome-wide co-expression correlations, and it also implements a suite of sophisticated computational tools for generating functional predictions with user-friendly visualizations. In the usage example provided here, we explore the role of BRCA1-NRF2 interplay in the context of bone cancer, demonstrating how Correlation AnalyzeR can be effectively implemented to generate and support novel hypotheses. CONCLUSIONS: Correlation AnalyzeR facilitates the exploration of poorly characterized genes and gene relationships to reveal novel biological insights. The database and all analysis methods can be accessed as a web application at https://gccri.bishop-lab.uthscsa.edu/correlation-analyzer/ and as a standalone R package at https://github.com/Bishop-Laboratory/correlationAnalyzeR .

Calcitonin negative neuroendocrine thyroid carcinoma: Case report and literature review

SUMMARY Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumor that originates in the parafollicular C cells of the thyroid gland. It is characterized by the synthesis and secretion of calcitonin. Usually, serum calcitonin is used as part of the diagnosis and follow-up of these patients. Few cases of MTC with negative calcitonin have been reported worldwide, whose diagnosis is a clinical challenge.

El carcinoma medular de tiroides (MTC) es un tumor neuroendocrino relativamente raro que se origina en las células C para foliculares de la glándula tiroides. Se caracteriza por la síntesis y secreción de calcitonina. Por lo general, la calcitonina sérica se utiliza como parte del diagnóstico y seguimiento de estos pacientes. Se han notificado pocos casos de MTC con calcitonina negativa en todo el mundo, cuyo diagnóstico es un desafío clínico.

Role of marijuana components on the regenerative ability of stem cells.

Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 µM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs. CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01). CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies. SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.

Intrathyroidal thymic carcinoma misdiagnosed as a medullary thyroid carcinoma.

The intrathyroidal thymic carcinoma is a rare neoplasm. The probable origin of this neoplasm is the presence of ectopic thymic tissue or remnants of the third and fourth branchial arch. The case of a 49-year-old female with an initial diagnosis of medullary thyroid cancer is presented. When she was operated for regional recurrence, 16 years later, the pathology report demonstrates the presence of a intrathyroidal thymic carcinoma. Intrathyroidal thymic carcinoma is considered an independent type of thyroid carcinoma because this entity has specific clinical-pathological characteristics similar to thymic carcinomas and different prognosis than known thyroid carcinomas. We present the case of a patient initially treated as having a medullary thyroid carcinoma who, upon presenting recurrence, the presence of intrathyroidal thymic carcinoma was demonstrated.

El carcinoma tímico intratiroideo es una neoplasia rara. El origen probable de esta neoplasia es la presencia de tejido tímico ectópico o de restos del tercer y cuarto arcos branquiales. Se presenta el caso de una mujer de 49 años con diagnóstico inicial de cáncer medular de tiroides. Cuando fue operada por recurrencia regional, 16 años después, se demostró la presencia de un carcinoma tímico intratiroideo, que se considera un tipo independiente de carcinoma tiroideo debido a que tiene características clínico-patológicas específicas similares a los carcinomas tímicos y un pronóstico diferente a los carcinomas de tiroides conocidos. Este caso se trató inicialmente como carcinoma medular de tiroides y al presentar recurrencia se demostró la presencia de un carcinoma tímico intratiroideo.

Reconstruction of Ewing Sarcoma Developmental Context from Mass-Scale Transcriptomics Reveals Characteristics of EWSR1-FLI1 Permissibility.

Ewing sarcoma is an aggressive pediatric cancer of enigmatic cellular origins typically resulting from a single translocation event t (11; 22) (q24; q12). The resulting fusion gene, EWSR1-FLI1, is toxic or unstable in most primary tissues. Consequently, attempts to model Ewing sarcomagenesis have proven unsuccessful thus far, highlighting the need to identify the cellular features which permit stable EWSR1-FLI1 expression. By re-analyzing publicly available RNA-Sequencing data with manifold learning techniques, we uncovered a group of Ewing-like tissues belonging to a developmental trajectory between pluripotent, neuroectodermal, and mesodermal cell states. Furthermore, we demonstrated that EWSR1-FLI1 expression levels control the activation of these developmental trajectories within Ewing sarcoma cells. Subsequent analysis and experimental validation demonstrated that the capability to resolve R-loops and mitigate replication stress are probable prerequisites for stable EWSR1-FLI1 expression in primary tissues. Taken together, our results demonstrate how EWSR1-FLI1 hijacks developmental gene programs and advances our understanding of Ewing sarcomagenesis.

Coriocarcinoma gástrico primario: reporte de caso / Primary gastric choriocarcinoma: a case report

El coriocarcinoma gástrico primario (CGP) es un tumor infrecuente. Debido a su rareza, su patogenia aún no es clara. El diagnóstico se basa en la inmunohistopatología, la cual es positiva para gonadotropina coriónica humana (hCG). Es una neoplasia altamente invasiva y de rápida diseminación hematógena, lo que conlleva a un pobre pronóstico. Se presenta el caso de una paciente mujer de 57 años con hemorragia digestiva alta asociada a baja de peso. La gastroscopia reporta, a nivel de cardias y región paracardial, lesión polipoidea ulcerada de 5x4 cm, con bordes circunscritos y sin presencia de infiltración de pared adyacente, con estigmas de sangrado reciente y anatomía patológica que informa neoplasia maligna pleomórfica ulcerada con inmunohistoquímica positiva para panqueratina. Ante la sospecha de carcinoma poco diferenciado y sin evidencia de metástasis, la paciente fue sometida a gastrectomía total y la patología fue compatible con coriocarcinoma. Por ello, posterior a la cirugía, se realiza estudio de hCG sérico con resultado de 714 mIU/ml, lo que confirmó aún más el diagnóstico. Se decide tratamiento adyuvante con quimioterapia y se realiza seguimiento tomográfico y serológico de hCG sin presencia de enfermedad activa.

Primary gastric choriocarcinoma (PGC) is an uncommon tumor. Due to its rarity, its pathogenesis is still unclear. The diagnosis is based on immunohistopathology, which is positive for human chorionic gonadotropin (hCG). It is a highly invasive and rapidly-disseminated hematogenous neoplasm, which leads to a poor prognosis. We present the case of a 57-year-old woman with upper gastrointestinal bleeding associated with weight loss. The gastroscopy showed, on the cardia and paracardial region, a 5x4-cm ulcerated polypoid lesion with circumscribed edges and without adjacent wall infiltration, with stigmas of recent bleeding and a pathological anatomy that demonstrates ulcerated pleomorphic malignancy with positive immunohistochemistry for pankeratin. Given the suspicion of poorly differentiated carcinoma and without evidence of metastasis, the patient underwent a total gastrectomy and the pathology was compatible with choriocarcinoma. Therefore, after the surgery, a serum hCG test was performed with a result of 714 mIU/ml, which further confirmed the diagnosis. Treatment with adjuvant chemotherapy was decided, and a tomographic and serological hCG follow-up was conducted, without the presence of active disease.

Perfil molecular y características clínico-patológicas del carcinoma mamario, con énfasis en la expresión del Ki 67: Experiencia inicial en instituto oncológico del norte del Perú / Molecular profile and clinical-pathological characteristics of the mammary carcinoma, with emphasis on the expression of Ki 67: Initial experience at the oncological institute of the north of Peru

Objetivo: Identificar el perfil molecular y las características clínicas y patológicas del carcinoma de mama de acuerdo a la variabilidad en la expresión del Ki 67. Material y métodos. Serie de casos, en el que se evaluaron 157 pacientes con diagnóstico anatomopatológico e inmunohistoquímico de cáncer de mama atendidas en el IREN Norte (Perú) durante el período 2008 ­ 2015. Se clasificaron los tumores en Luminal A, Luminal B, HER2 y Triple negativo. Se utilizo dos puntos de corte para evaluar el Ki 67:> 14% y > 20%, de acuerdo a lo sugerido en St. Gallen 2011 y 2013 respectivamente. Resultados. En el grupo de pacientes con Ki 67 > 20%, el subtipo molecular que predominó fue el Luminal B (n = 54; 34%). El tamaño tumoral más frecuente se ubicó en el grupo de > 2 a < 5 cm. (T2), representando 56% en el subtipo Luminal B, 28% en Luminal A, 69% en HER2 y 41% en el Triple negativo. En los pacientes con Ki 67 > 14%, el subtipo molecular y el tamaño tumoral predominante también fue el Luminal B (n = 73, 46%) y el T2. El tipo histológico más común fue el carcinoma ductal independientemente del punto de corte del valor de Ki 67. Conclusiones. La utilidad del valor porcentual del Ki 67 evaluado en dos puntos de corte es controversial; en nuestro estudio el perfil molecular y las características clínico-patológicas de cáncer de mama fueron relativamente similares en relación a Luminal A y Luminal B.

Objetive: Identify the molecular profile and the clinical and pathological characteristics of breast carcinoma according to the variability in Ki 67 expression. Material and methods. Case series, in which 157 patients with an anatomopathological and immunohistochemical diagnosis of breast cancer treated at IREN Norte (Peru) were evaluated during the period 2008-2015. The tumors were classified into Luminal A, Luminal B, HER2 and Triple Negative. Two cut-off points were used to evaluate Ki 67: > 14% and > 20%, according to what was suggested in St. Gallen 2011 and 2013 respectively. Results. In the group of patients with Ki 67 > 20%, the mol ecul ar subtype that predominated was Luminal B (n = 54, 34%). The most frequent tumor size was in the group of > 2 to < 5 cm. (T2), representing 56% in the Luminal B subtype, 28% in Luminal A, 69% in HER2 and 41% in the Triple negative. In patients with Ki 67 > 14%, the molecular subtype and the predominant tumor size was also Luminal B (n = 73, 46%) and T2. The most common histological type was ductal carcinoma regardless of the cut-off point of the Ki 67 value Conclusions. The utility of the percentage value of Ki 67 evaluated at two cut points is controversial; in our study, the molecular profile and clinical-pathological characteristics of breast cancer were relatively similar in relation to Luminal A and Luminal B.