Molecular characterization of triple negative breast cancer formaldehyde-fixed paraffin-embedded samples by data-independent acquisition proteomics.

Triple negative breast cancer accounts for 15%-20% of all breast carcinomas and is clinically characterized by an aggressive phenotype and poor prognosis. Triple negative tumors do not benefit from targeted therapies, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of 125 formalin-fixed paraffin-embedded samples from patients diagnosed with non-metastatic triple negative breast cancer were analyzed using data-independent acquisition + in a LTQ-Orbitrap Fusion Lumos mass spectrometer coupled to an EASY-nLC 1000. 1206 proteins were identified in at least 66% of the samples. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were combined to characterize proteomics-based molecular groups. Two molecular groups were defined with differences in biological processes such as glycolysis, translation and immune response. These two molecular groups showed also several differentially expressed proteins. This clinically homogenous dataset may serve to design new therapeutic strategies in the future.

One-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastasis in endometrial cancer.

OBJECTIVE: To evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the diagnosis of sentinel lymph node (SLN) metastasis compared with histopathological examination in patients with endometrial carcinoma. METHODS: A total of 94 SLNs from 34 patients with endometrial carcinoma were enrolled. The central 1-mm portion of each node was subjected to semi-serial sectioning, sliced at 200-µm intervals and examined by hematoxylin and eosin and cytokeratin 19 (CK19) immunohistochemical staining, and the remaining tissue was analysed by OSNA using CK19 mRNA. The accuracy of the OSNA assay was evaluated based on histopathological diagnosis. RESULTS: Histologically, 89 SLNs were determined to be metastasis negative, and the remaining five SLNs were metastasis positive. Using the breast cancer cutoff value for detecting lymph node metastasis (OSNA criteria for breast cancer, >250copies/µl) the sensitivity of the OSNA assay was 100%; specificity was 87.6%; diagnostic accuracy was 88.3%. Discordant results were recorded for 11 of 94 SLNs. In all 11 cases, a positive result was given by the OSNA assay but not by histopathological examination. In two SLNs from the same patient, histopathological examination revealed the presence of benign epithelial inclusions that were CK19 positive; both SLNs yielded a positive result in the OSNA assay (true-false positive). All remaining nine histologically-negative/OSNA-positive SLNs were classified as micrometastasis (+) by the OSNA assay. CONCLUSION: The OSNA assay shows high sensitivity and specificity, which suggests its utility as a novel tool for the molecular detection of SLN metastasis in patients with endometrial carcinoma.

Case report: lupus nephritis with autoantibodies to complement alternative pathway proteins and C3 gene mutation.

BACKGROUND: Glomerulonephritis is one of the most severe complications of lupus, a systemic disease with multi-organ involvement, with tissue damage produced mainly by complement activation. As a result of this activation, patients with active lupus present hypocomplementemia during disease flares, but C3 and C4 levels are recovered between episodes. CASE PRESENTATION: We present a patient who suffered two lupus nephritis episodes in 5 years, achieving complete remission with treatment after both of them, but with C3 levels persistently below normal range. Genetic study revealed that the patient carried a mutation in heterozygosis in the C3 gene. Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin) were found. Functional assays showed that these autoantibodies cause alternative pathway activation. CONCLUSION: This case is the first reported of a heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that the tissue damage is restricted to the kidney.

Surgical Interest of an Accurate Real-World Prediction of Primary Systemic Therapy Response in HER2 Breast Cancers.

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancers (BC) present the highest rates of pathological response to primary systemic therapy (PST), but they are also the ones that tend to be larger at diagnosis, with microcalcifications and, often, with axillary involvement. If we do not have a reliable method to predict the degree of response, we may not be able to transfer the benefits of PST to surgery. The post-PST surgery planning is guided by the findings in the magnetic resonance imaging (MRI), whose predictive capacity, although high, is far from optimal. Thus, it seems interesting to find other variables to improve it. A retrospective observational study including women with HER2 BC treated with PST and further surgery was conducted. Information regarding clinical, radiological, and histopathological variables was gathered from a total of 132 patients included. Radiological complete response (rCR) was achieved in 65.9% of the sample, and pathological complete response (pCR), according to Miller and Payne criteria, in 58.3% of cases. A higher Ki67 value, the absence of Hormonal Receptors expression, and an rCR was significantly related to a pCR finding. This information impacts directly in surgery planning, as it permits adjustment of the breast resection volume.

The Clinical Impact of Neoadjuvant Endocrine Treatment on Luminal-like Breast Cancers and Its Prognostic Significance: Results from a Single-Institution Prospective Cohort Study.

Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast- conserving surgery (BCS) rates, provides an opportunity for us to assess in vivo NET effectiveness, and allows us to study any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness. Methods: From 2016 to 2020, a single-institution cohort of patients, treated with NET and further surgery, was evaluated. In patients with Ki67 ≥ 10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered. Results: A total of 115 estrogen receptor-positive (ER+)/HER2-negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0−6.0). The median maximum size in the surgical sample was 40% smaller than the pretreatment size measured by ultrasound (p < 0.0001). The median pretreatment Ki67 expression was 20.0% (IQR: 12.0−30.0), and was reduced to 5.0% (IQR: 1.8−10.0) after four weeks, and to 2.0% (IQR: 1.0−8.0) in the surgical sample (p < 0.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold change after four weeks was significantly related to a PEPI score of zero (p < 0.002). No differences were observed between luminal A- and B-like tumors, with regard to fold change and PEPI score. Conclusions: In our cohort, NET was proven to be effective for tumor size and Ki67 downstaging. This resulted in a higher rate of conservative surgery, aided in therapeutic decision making, provided prognostic information, and constituted a safe and well-tolerated approach.

SARS-CoV-2 infection associated with monoclonal gammopathy. A case report based on the study of minimally invasive ultrasound-guided autopsy.

Coronavirus disease-2019 (COVID-19) is a global public health emergency with numerous clinical facets, including acute kidney injury and acute cerebrovascular disease. Further knowledge of its various pathogenic mechanisms is essential, including coagulation disorders. Monoclonal gammopathy is characterized by the overproduction of a monoclonal immunoglobulin caused by clonal proliferation. Using a postmortem study of ultrasound-guided percutaneous core biopsies, the aim of this report is to present our observations on the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection pathology associated with monoclonal gammopathy. The clinical presentation was acute renal failure. Pathological findings revealed kappa light chain cast nephropathy. SARS-CoV-2 immunohistochemistry was positive in some renal tubular cells. Another notable finding was the presence of a high density of alveolar megakaryocytes, which probably explained the final outcome (acute cerebrovascular disease). Immunohistochemical study for SARS-CoV-2 does not verify the pathogenic effect of the virus and thus its contribution to the acute kidney injury.

Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (including patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation.

[Evaluation of pathological response to neoadjuvant chemotherapy in breast cancer: correlation with molecular phenotype]. / Evaluación de la respuesta patológica a quimioterapia neoadyuvante en cáncer de mama: correlación con el fenotipo molecular.

INTRODUCTION AND OBJECTIVE: Breast cancer can be classified into different molecular subtypes with important therapeutic and prognostic implications. Neoadjuvant chemotherapy (NAC) increases the possibility of performing conservative surgery and allows in vivo testing of the sensitivity of the tumor. Our aim was to evaluate the pathological response to NAC in relation to the molecular phenotype and the different definitions of the pathological response. PATIENTS: 228 patients treated with NAC and subsequent surgery between 2012 and 2018 were selected from our breast cancer database. Molecular phenotypes were established based on the criteria of the St Gallen 2013 Conference. Pathological response was evaluated following Miller-Payne (breast) and Sataloff (axilla) classification systems. RESULTS: The most frequent molecular phenotype was luminal B/HER2 negative (30.3%), followed by luminal B/HER2 positive (26.3%), triple negative (24.6%), HER2 positive (13.2%), and luminal A (5.7%). The rate of pathological complete response (pCR) was 35.5% in breast and 15.3% in axilla. The rate of pCR considering breast and axilla together was 26.8%. The molecular phenotype with the highest rate of pCR was HER2 positive (66.7%) followed by triple negative (30.4%), luminal B/HER2 positive (21.7%), luminal B/HER2 negative (14.5%), and luminal A (7.7%) (p < 0.001). The same results were found with the different definitions of pCR we evaluated. CONCLUSIONS: Complete pathological response to NAC in breast cancer depends largely on the molecular phenotype of the tumor, regardless of the definition of pCR, with the highest response rates in the breast and axilla in the HER2 positive and triple negative phenotypes.

Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma.

Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours.

Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling.

Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors.

One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA).

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 µm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/µL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma.

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented -MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

High-throughput 3-dimensional culture of epithelial ovarian cancer cells as preclinical model of disease.

BACKGROUND: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification. METHODS AND RESULTS: In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions. CONCLUSIONS: We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development.

Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes.

BACKGROUND/AIM: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. RESULTS: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. CONCLUSION: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.

Tratamiento percutáneo del cáncer infiltrante de mama en estado clínico I/II mediante crioablación en pacientes sin indicación de cirugía axilar / Percutaneous cryoablation of clinical stage I/II breast cancer in patients without indication for axillary surgery

Objetivo: revisar la eficacia del tratamiento percutáneo del cáncer infiltrante de mama (CM) mediante crioablación guiada con ecografía en pacientes con estadio clínico I/II en las que se desestima la cirugía axilar. Métodos: se recogieron de nuestros archivos las pacientes con CM en estadio clínico I/II que fueron tratadas mediante crioablación guiada con ecografía en las que se desestimó la cirugía axilar. Se seleccionaron las pacientes que tuvieron un seguimiento mínimo de 12 meses. Las revisiones fueron ecográficas: la primera entre 1 y 2 meses (para valorar lesiones residuales por tratamiento incompleto) y posteriormente semestrales (para valorar las recidivas). Las lesiones residuales y las recidivas se confirmaron con BAG y en todos los casos se valoró el tratamiento con nueva crioablación (de rescate). Se analizó la eficacia del procedimiento en función del control local en la mama. Resultados: desde marzo de 2019 hasta septiembre de 2022 fueron tratadas mediante crioablación guiada con ecografía 84 pacientes con 92 CM en estadio clínico I/II en las que la cirugía axilar fue desestimada. Se estudiaron retrospectivamente las 43 pacientes (58-96 años, media 83, DE ±7,64) con 48 CM (entre 5 y 60 mm, media 17, DE ±13,75) que tuvieron un seguimiento mínimo de 12 meses (entre 12 y 40 meses, media 20). Hubo 2 pacientes con tratamiento incompleto en la primera ecografía y 5 pacientes recidivaron (entre 9 y 27 meses, media 17). Todas se trataron con crioablaciones de rescate. El control local a los 12 meses fue del 90,5% (probabilidad 0,905 error estándar 0,045) y en el 95% de las pacientes (41/43) se consiguió controlar localmente el CM. Fallecieron 6 pacientes, 3 por evolución del CM y 3 por otras causas. Todos los procedimientos fueron bien tolerados y no hubo complicaciones graves. (AU)

Objective: To review the efficacy of percutaneous treatment of infiltrating breast cancer (BC) by ultrasound-guided cryoablation in patients with clinical stage I/II without indication for axillary surgery Methods: Patients with clinical stage I/II BC who were treated by ultrasound-guided cryoablation in whom axillary surgery was ruled out were collected from our files. Patients who had a minimum follow-up of 12 months were selected. The ultrasound follow up were: the first between 1-2 months (to assess residual lesions due to incomplete treatment) and subsequently every six months (to assess recurrences). Residual lesions and recurrences were confirmed with CNB and in all cases treatment with new (salvage) cryoablation was considered. The efficacy of the procedure was assessed on local control in the breast. Results: Between March 2019 and September 2022, 84 patients with 92 BC in clinical stage I/II were treated with ultrasound-guided cryoablation without indication for axillary surgery. The inclusion criteria of the retrospective study were met by 43 patients (58-96 years, mean 83, SD ±7,64) with 48 BC (between 5-60mm, mean 17, SD ±13,75) who were reviewed during a mean period of 20 months (between 12-40 months). There were two patients with incomplete treatment at the first ultrasound and five patients relapsed (between 9-27 months, mean 17). All were treated with salvage cryoablation. Local control at 12 months was 90.5% (probability 0.905 standard error 0.045) and in 95% of patients (41/43) the BC was locally controlled. Six patients died, three due to progression of the BC and three due to other causes. All procedures were well tolerated and there were no serious complications. (AU)

Primary Leiomyosarcoma of the Ovarian Vein: Case Report and Literature Review.

Primary leiomyosarcoma arising from the ovarian vein is extremely rare, with only 10 cases reported in the literature. We report on a case of leiomyosarcoma of the left ovarian vein in a 67-year-old woman who presented with abdominal discomfort. Pelvic ultrasound revealed a large, solid, irregular mass in close relation to the left ovary. The patient subsequently underwent a total hysterectomy with bilateral salpingo-oophorectomy. Histologically, the tumor was composed of interlacing fascicles of spindle cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Mitotic activity was high, with 24 mitoses in 10 high-power fields. Areas of necrosis and hemorrhage were present within the tumor. Immunohistochemically, the tumor cells showed diffuse immunoreactivity for vimentin, muscle-specific actin, desmin, and caldesmon. The patient received chemotherapy postoperatively but subsequently developed disseminated metastatic disease (lung, liver, iliac lymph nodes, and peritoneum). Primary leiomyosarcomas arising from the ovarian vein are aggressive neoplasms, and the prognosis correlates with stage.

Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.

PURPOSE: To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. METHODS: Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). RESULTS: The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). CONCLUSIONS: This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.

SARS-CoV-2 infection associated with monoclonal gammopathy. A case report based on the study of minimally invasive ultrasound-guided autopsy

Coronavirus disease-2019 (COVID-19) is a global public health emergency with numerous clinical facets, including acute kidney injury and acute cerebrovascular disease. Further knowledge of its various pathogenic mechanisms is essential, including coagulation disorders. Monoclonal gammopathy is characterized by the overproduction of a monoclonal immunoglobulin caused by clonal proliferation. Using a postmortem study of ultrasound-guided percutaneous core biopsies, the aim of this report is to present our observations on the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection pathology associated with monoclonal gammopathy. The clinical presentation was acute renal failure. Pathological findings revealed kappa light chain cast nephropathy. SARS-CoV-2 immunohistochemistry was positive in some renal tubular cells. Another notable finding was the presence of a high density of alveolar megakaryocytes, which probably explained the final outcome (acute cerebrovascular disease). Immunohistochemical study for SARS-CoV-2 does not verify the pathogenic effect of the virus and thus its contribution to the acute kidney injury.(AU)

La enfermedad por coronavirus de 2019 (COVID-19) es una emergencia sanitaria pública global con numerosas facetas clínicas que incluyen enfermedad renal aguda y enfermedad cerebrovascular aguda. Es necesario un conocimiento adicional de su mecanismo patogénico. Los trastornos de coagulación están claramente incluidos en dichos mecanismos. La gammapatía monoclonal se caracteriza por la sobreproducción de inmunoglobulina monoclonal causada por proliferación clonal. Utilizando un estudio postmortem de biopsias percutáneas ecoguiadas, el objetivo de este informe es presentar nuestras observaciones sobre la patología del síndrome respiratorio agudo severo por infección de coronavirus 2 (SARS-CoV-2) con gammapatía monoclonal. La presentación clínica fue insuficiencia renal aguda. Los hallazgos patológicos revelaron nefropatía por cilindros de cadenas ligeras kappa. La inmunohistoquímica de SARS-CoV-2 fue positiva en ciertas células tubulares renales. La presencia de megacariocitos alveolares (alta densidad) fue un hallazgo notable, que explica probablemente el resultado final del paciente (enfermedad cerebrovascular aguda). El estudio inmunohistoquímico frente a SARS-CoV-2 no verifica el efecto patogénico del virus y, por tanto, su contribución a la nefropatía aguda.(AU)

Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report.

BACKGROUND: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant head and neck cancer thought to originate from the olfactory epithelium. It typically invades contiguous structures at presentation. We report a very rare case of multifocal and ectopic ONB. CASE REPORT: A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses. Histopathological diagnosis after endoscopic resection established bilateral olfactory neuroblastoma of the ethmoid sinuses. The patient received postoperative radiotherapy. He remains free of disease 4 years after treatment. CONCLUSIONS: To the best of our knowledge this is the second documented case of multifocal ectopic olfactory neuroblastoma. Clinicians should consider ONB in the differential diagnosis of bilateral synchronous nasal and paranasal masses to avoid delayed diagnosis. Endoscopic resection of ONB could be an option in selected cases.