Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer.

BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS: dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and ST-CD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2- was associated with high IT-CD8 (P = 0.009). H. pylori-negative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION: TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Apoptosis Pathway-Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma.

ABSTRACT: Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies.

Association between PIK3CA Mutations in Blood and Tumor-Infiltrating Lymphocytes in Peruvian Breast Cancer Patients.

OBJECTIVE: To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. MATERIALS AND METHODS: This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. RESULTS: We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). CONCLUSION: Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.

The relationship between tumour infiltrating lymphocytes, Epstein-Barr virus and Helicobacter pylori infection in gastric cancer.

Objective: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections have been extensively recognised as gastric cancer (GC) triggers, and recent publications suggest they could behave as predictive markers for immune-modulating therapies. Tumour-infiltrating lymphocytes (TILs) have also been identified as a predictive biomarker for immunotherapy in different malignancies. This study aimed to investigate the association between EBV and HP infection with TIL levels in GC. Methods: TIL evaluation in haematoxylin-eosin was performed by a pathologist and density of CD3, CD8 and CD163 positive (immunohistochemistry staining) immune cells was calculated with the use of digital pathology software. EBV infection was detected by in situ hybridisation (ISH) and by quantitative polymerase chain reaction (qPCR). Methylation status of EBV-related genes was detected by PCR and a methylome analysis was performed by the Illumina Infinium MethylationEPIC BeadChip. HP status was detected by qPCR. Results: We included 98 resected GC Peruvian cases in our evaluation. Median TIL percentage was 30. The proportion of EBV+ detected by ISH was 24.1%, of EBV+ detected by qPCR was 41.8%, while 70% showed methylation of EBV-related genes, and 58.21% of cases were HP+. Younger age (p = 0.024), early stages (p = 0.001), HP+ (p = 0.036) and low CD8 density (p = 0.046) were associated with longer overall survival (OS). High TIL level was associated with intestinal subtype (p < 0.001), with grade 2 (p < 0.001), with EBV qPCR+ (p = 0.001), and with methylation of EBV-related genes (p = 0.007). Cases with high TIL level and cases that are EBV positive share eight genes with similarly methylated status in the metabolomic analysis. High CD8 density was associated with EBV PCR+ (p = 0.012) and HP- (0.005). Conclusion: Lower CD8 density and HP+ predict longer OS. High TIL level is associated with EBV+ and methylation of EBV-related genes, while lower CD8 density is associated with HP+ GC.

Human Papillomavirus, Cytomegalovirus Infection and P16 Staining in Breast Tumors from Peruvian Women.

OBJECTIVE: To evaluate the frequency distribution of viral infections in Peruvian Breast Cancer (BC) lesions and its association with clinicopathological features. Additionally, a prospective evaluation of p16 and Tumor-infiltrating lymphocytes (TIL) levels were performed for developing a comprehensive analysis. METHODS: Detection of high risk- human papillomavirus (HR- HPV) through qPCR was performed in 447 BC and 79 non-cancer frozen samples. Paired paraffin samples from 238 BC were stained with Human cytomegalovirus (HCMV) and p16 immunohistochemistry. TIL was calculated in 397 BC cases. RESULTS: HCMV was positive in 72.5%. HR- HPV was detected in 2.9% of BC and 1.3% of non-malignant samples. P16+ was found in 28.15% and median TIL percentage was 30. HR- HPV infection was associated with non-ductal histology (p=0.003) and p16+ (p=0.017). Positive P16+ was associated with higher T stage (p=0.022), grade (p=0.009), TIL level (p=0.002), and triple-negative phenotype (p=0.021). CONCLUSION: HCMV is frequent, but HR- HPV infection is unusual in Peruvian BC. P16+ is associated with HR- PVH infection, high TIL and aggressive features.

Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16INK4a status.

BACKGROUND: Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16INK4a in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. METHODS: HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16INK4a immunohistochemistry. RESULTS: HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16INK4a positivity were observed among HPV positive OPC/OCC cases compared to LC cases. CONCLUSIONS: Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

A biomarker study in Peruvian males with breast cancer.

BACKGROUND: Breast cancer (BC) frequency in males is extremely low and tumor features vary from its female counterpart. Breast cancer clinical and pathological features differ by race in women. Tumor infiltrating lymphocyte (TIL) levels, mismatch repair (MMR) protein loss, androgen receptor (AR) expression, and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC. There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC. AIM: To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODS: This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves. RESULTS: The median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05). CONCLUSION: Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.

Biological characteristics of a sub-population of cancer stem cells from two triple-negative breast tumour cell lines.

Triple-negative breast tumours (TNBTs) make up 15-20% of all breast tumours. There is no treatment for them, and the role that cancer stem cells (CSCs) have in carcinogenesis is still unclear, so finding markers and therapeutic targets in CSC exosomes requires these cells to exist as a homogeneous cell population. The objective of this work was to determine differences in ultrastructural morphology, proliferative capacity, and mouse-xenotransplantation characteristics of the MDA-MB-231 and MDA-MB-436 TNBT cell lines with the CD44 high /CD24 low phenotype in order to study their exosomes. The results show that the CD44 high /CD24 low MBA-MB-231 cells had a population doubling time of 41.56 h, compared to 44.79 h in the MDA-MB-436 cell line. After magnetic immunoseparation, 18.75% and 14.56% of the stem cell population of the MDA-MB-231 and MDA-MB-436 cell lines, respectively, were of the CD44 high /CD24 low phenotype, which were expanded to reach purities of 80.4% and 87.6%. The same expanded lineage in both cell lines was shown to possess the pluripotency markers Nanog and Oct4. Under a scanning electron microscope, the CD44 high /CD24 low lineage of the MBA-MD-231 cell line formed groups of more interconnected cells than this lineage of the MBA-MD-436 line. A total of 16% of the mice inoculated with the CD44 high /CD24 low lineage of either cell line presented tumours of the breast, lung, and submandibular ganglia, in whose tissues variable numbers of inoculated cells were found 30 days post-inoculation. By magnetic immunoselection, it was possible to isolate in similar quantities and characterize, expand, and xenotransplant the CD44 high /CD24 low lineage of the MDA-MB-231 and MDA-MB-436 cell lines. The former cell line has greater proliferative capacity, the two lines differ under scanning electron microscopy in how they intercommunicate, and both cell lines induce new tumours in mice and persist at least 30 days post-inoculation in the transplanted animal so their exosomes would also be different.

COVID-19 en pacientes con cáncer: revisión sistemática / COVID-19 in cancer patients: a systematic review

RESUMEN Objetivo: El desarrollo de cuadros severos y la muerte por COVID-19 son más frecuentes en poblaciones con comorbilidades. Algunos estudios describen mayor frecuencia de cuadros severos en pacientes con cáncer. Esta revisión sistemática tiene por objetivo describir el riesgo de infección y de presentar un cuadro severo por COVID-19 en pacientes oncológicos. Materiales y métodos: Se realizó una revisión sistemática mediante una búsqueda de la literatura en PubMed y Scopus hasta mayo de 2020. Se amplió la inclusión de estudios con una búsqueda secundaria. Resultados: La búsqueda inicial identificó 2192 registros, de los que se incluyeron 17 publicaciones con al menos 10 pacientes oncológicos infectados. Además, se incluyeron cinco artículos de la búsqueda adicional de las referencias citadas en los 17 artículos. Diez publicaciones provenían de autores chinos. El análisis de la información indicó que la infección es más frecuente en pacientes con cáncer, y las frecuentes visitas terapéuticas al establecimiento de salud serían las causantes. La COVID-19 severa es más frecuente en pacientes con cáncer, y factores como la edad avanzada, comorbilidades asociadas, estadio avanzado y marcadores séricos de inflamación incrementan la severidad del cuadro. Estudios iniciales realizados en China encuentran que el uso de tratamiento antineoplásico sistémico podría también ser un factor predisponente. Conclusiones: El riesgo de infección y de desarrollar cuadro severo por COVID-19 es mayor en la población oncológica.

ABSTRACT Objective: Development of severe disease and death from COVID-19 is more frequent in patients with comorbidities. Some studies report an increased frequency of severe COVID-19 in cancer patients. This review aims to describe the risk of infection and developing severe COVID-19 in cancer patients. Materials and methods: A systematic review was carried out through an exhaustive search of literature in PubMed and Scopus until May 2020. A secondary search was performed to include more studies. Results: The initial search identified 2,192 records, which included 17 publications with at least 10 infected cancer patients. Also, 5 articles were added from the additional search of the references cited by those 17 publications. Ten publications were from Chinese authors. Data analysis showed that COVID-19 infection is more frequent in cancer patients, and frequent therapeutic visits to the healthcare facility may be the cause. The presence of neoplasia predisposed patients to develop severe disease. Advanced age, associated comorbidities, advanced malignancy, and the presence of serum inflammatory markers increased the risk of developing severe disease. Initial studies indicate that the use of systemic treatment may also be a predisposing factor. Conclusions: The risk of becoming infected by COVID-19 and developing severe disease is higher in the oncological population.

Detection of Helicobacter pylori in gastric cancer tissue through histopathology, immunohistochemistry and real-time reverse transcription-PCR.

Aim:Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results:H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.

COVID-19 in cancer patients: a systematic review. / COVID-19 en pacientes con cáncer: revisión sistemática.

OBJECTIVE: Development of severe disease and death from COVID-19 is more frequent in patients with comorbidities. Some studies report an increased frequency of severe COVID-19 in cancer patients. This review aims to describe the risk of infection and developing severe COVID-19 in cancer patients. MATERIALS AND METHODS: A systematic review was carried out through an exhaustive search of literature in PubMed and Scopus until May 2020. A secondary search was performed to include more studies. RESULTS: The initial search identified 2,192 records, which included 17 publications with at least 10 infected cancer patients. Also, 5 articles were added from the additional search of the references cited by those 17 publications. Ten publications were from Chinese authors. Data analysis showed that COVID-19 infection is more frequent in cancer patients, and frequent therapeutic visits to the healthcare facility may be the cause. The presence of neoplasia predisposed patients to develop severe disease. Advanced age, associated comorbidities, advanced malignancy, and the presence of serum inflammatory markers increased the risk of developing severe disease. Initial studies indicate that the use of systemic treatment may also be a predisposing factor. CONCLUSIONS: The risk of becoming infected by COVID-19 and developing severe disease is higher in the oncological population.

OBJETIVO: El desarrollo de cuadros severos y la muerte por COVID-19 son más frecuentes en poblaciones con comorbilidades. Algunos estudios describen mayor frecuencia de cuadros severos en pacientes con cáncer. Esta revisión sistemática tiene por objetivo describir el riesgo de infección y de presentar un cuadro severo por COVID-19 en pacientes oncológicos. MATERIALES Y MÉTODOS: Se realizó una revisión sistemática mediante una búsqueda de la literatura en PubMed y Scopus hasta mayo de 2020. Se amplió la inclusión de estudios con una búsqueda secundaria. RESULTADOS: La búsqueda inicial identificó 2192 registros, de los que se incluyeron 17 publicaciones con al menos 10 pacientes oncológicos infectados. Además, se incluyeron cinco artículos de la búsqueda adicional de las referencias citadas en los 17 artículos. Diez publicaciones provenían de autores chinos. El análisis de la información indicó que la infección es más frecuente en pacientes con cáncer, y las frecuentes visitas terapéuticas al establecimiento de salud serían las causantes. La COVID-19 severa es más frecuente en pacientes con cáncer, y factores como la edad avanzada, comorbilidades asociadas, estadio avanzado y marcadores séricos de inflamación incrementan la severidad del cuadro. Estudios iniciales realizados en China encuentran que el uso de tratamiento antineoplásico sistémico podría también ser un factor predisponente. CONCLUSIONES: El riesgo de infección y de desarrollar cuadro severo por COVID-19 es mayor en la población oncológica.

Helicobacter Pylori Detected in Tap Water of Peruvian Patients with Gastric Cancer.

OBJECTIVE: To evaluate the correlation between the presence of H. pylori in paired samples of tap water and gastric cancer (GC) lesion in Lima city (Peru). MATERIAL AND METHODS: Gastric tissue and tap-water samples were prospectively collected from 82 Gastric Cancer who lived in Lima. HspA and ureA genes were evaluated by qPCR in the samples.  Results: The median age of patients with GC was 63 years, 52.4% were men and stage-II in 36.6%. A home-living time> 10 years was reported in 84.1% of patients. Boiling water treatment was indicated in 85.4% of cases. H. pylori was detected in 69.5% of gastric tissues and in 12.2% of analyzed tap-water. There was no differences in gastric infection rates among those with or without water contamination (70% vs. 69.4%, p=0.971). Conclusion & Impact: H. pylori was found in tap-water samples, however, detection rates were lower than in gastric cancer samples. Other sources of infection transmission should be investigated.

Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies.

Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.

Prevalence of Helicobacter pylori Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer.

PURPOSE: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. PATIENTS AND METHODS: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. RESULTS: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. CONCLUSION: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

Distribution of tumor-infiltrating immune cells in glioblastoma.

AIM: Evaluation of features related to infiltrating immune cell level in glioblastoma. METHODS: Tumor-infiltrating lymphocytes (TILs) through H&E staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163) levels through immunohistochemistry were evaluated through digital analysis. RESULTS: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was associated with higher age (p = 0.044) and recursive partitioning analysis = 4. Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001), radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were associated with longer overall survival. CONCLUSION: Macrophages are more frequent than TILs. Some subsets are associated with clinical features.

Critical review of axillary recurrence in early breast cancer.

Around 2% of early breast cancer cases treated with axillary lymph node dissection (ALND) underwent axillary recurrence (AR) and it has a deleterious effect in prognosis. Different scenarios have incorporated Sentinel Lymph Node (SLN) Biopsy (SLNB) instead of ALND as part of the standard treatment and more effective systemic treatment has also been incorporated in routine management after first curative surgery and after regional recurrence. However, there is concern about the effect of SLNB alone over AR risk and how to predict and treat AR. SLN biopsy (SLNB) has been largely accepted as a valid option for SLN-negative cases, and recent prospective studies have demonstrated that it is also safe for some SLN-positive cases and both scenarios carry low AR rates. Different studies have identified clinicopathological factors related to aggressiveness as well as high-risk molecular signatures can predict the development of locoregional recurrence. Other publications have evaluated factors affecting prognosis after AR and find that time between initial treatment and AR as well as tumor aggressive behavior influence patient survival. Retrospective and prospective studies indicate that treatment of AR should include local and systemic treatment for a limited time.

[Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru]. / Tuberculosis que imita cáncer: casos derivados al Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú.

Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.

La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.