A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9-12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer.

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.

SARS-CoV-2 seroprevalence and respiratory disease disability claims in Mexico City Metropolitan Area.

OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.

Prevalence of SARS-CoV-2 antibodies in cancer patients and healthcare workers vaccinated with two doses of BNT162b2 or AZD122. A propensity analysis.

BACKGROUND: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. OBJECTIVES: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. MATERIAL AND METHODS: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. RESULTS: One-hundred and twenty-seven CPs (22%) and 439 HCWs (78%) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. CONCLUSIONS: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.

ANTECEDENTES: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). OBJETIVOS: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. MATERIAL Y MÉTODOS: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. RESULTADOS: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. CONCLUSIONES: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.

Cancer Prevention Behaviors in Workers of a Referral Cancer Center in Mexico City: A Pilot Study on Early Detection Awareness for Cancer.

BACKGROUND: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City. METHODS: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated with prevention behaviors were identified by logistic regression. RESULTS: We recruited 301 workers; 77% were women. The median self-reported BMI was 26.4 kg/m2, 9.97% smoked, 78% drank alcohol, and 89% did not get at least 150 min/week of physical activity. In women, age (OR = 1.3 95%CI 1.01-1.06) and physical activity of 150 min/week (OR = 2.52 95% CI 1.28-4.96) were associated with cancer prevention behaviors. No risk factors were associated with healthy behaviors among men. CONCLUSION: Health workers may have unhealthy lifestyles and behaviors, is essential to create supportive environments to promote cancer prevention counseling and programs effectively.

A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Emergence and spread of the potential variant of interest (VOI) B.1.1.519 of SARS-CoV-2 predominantly present in Mexico.

SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report the identification of a potential variant of interest, harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B.1.1.519, that rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

Tumor microenvironment differences between primary tumor and brain metastases.

The present review aimed to discuss contemporary scientific literature involving differences between the tumor microenvironment (TME) in melanoma, lung cancer, and breast cancer in their primary site and TME in brain metastases (BM). TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, natural killer cells, and other cells can perpetuate and progress carcinogenesis via the secretion of molecules. Oxygen concentration, growth factors, and receptors in TME initiate angiogenesis and are examples of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood-brain barrier (BBB). After traversing BBB, these cells have to survive by producing various cytokines, chemokines, and mediators to modify their new TME. The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer.

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

Role of pelvic and para-aortic lymphadenectomy in abandoned radical hysterectomy in cervical cancer.

BACKGROUND: Cervical cancer (CC) occupies fourth place in cancer incidence and mortality worldwide in women, with 560,505 new cases and 284,923 deaths per year. Approximately, nine of every ten (87%) take place in developing countries. When a macroscopic nodal involvement is discovered during a radical hysterectomy (RH), there is controversy in the literature between resect macroscopic lymph node compromise or abandonment of the surgery and sending the patient for standard chemo-radiotherapy treatment. The objective of this study is to compare the prognosis of patients with CC whom RH was abandoned and bilateral pelvic lymphadenectomy and para-aortic lymphadenectomy was performed with that of patients who were only biopsied or with removal of a suspicious lymph node, treated with concomitant radiotherapy/chemotherapy in the standard manner. METHODS: A descriptive and retrospective study was conducted in two institutions from Mexico and Colombia. Clinical records of patients with early-stage CC programmed for RH with an intraoperative finding of pelvic lymph, para-aortic nodes, or any extracervical involvement that contraindicates the continuation of surgery were obtained. Between January 2007 and December 2012, 42 clinical patients complied with study inclusion criteria and were selected for analysis. RESULTS: In patients with CC whom RH was abandoned due to lymph node affectation, there is no difference in overall survival or in disease-free period between systematic lymphadenectomy and tumor removal or lymph node biopsy, in pelvic lymph nodes as well as in para-aortic lymph nodes, when these patients receive adjuvant treatment with concomitant radiotherapy/chemotherapy. CONCLUSIONS: This is a hypothesis-generator study; thus, the recommendation is made to conduct randomized prospective studies to procure better knowledge on the impact of bilateral pelvic and para-aortic lymphadenectomy on this group of patients.

Histology as Prognostic Factor in Early-Stage Cervical Carcinoma. Experience in a Third-Level Institution.

BACKGROUND: Cervical carcinoma (CC) is one of the most frequent neoplasms, especially in developing countries. The most common histopathological type is squamous cell carcinoma (SCC), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Prognosis according to histological type is controversial. OBJECTIVE: The objective of this study is to describe and compare the prognoses of the most common histologies of CC in the early stages. MATERIALS AND METHODS: We reviewed records of patients attended at the Instituto Nacional de Cancerología of Mexico with CC surgically treated Stages IA2-IB1 and IIA1, including the histological types SCC, AC, and ASC. Patients who had another malignant neoplasm, cervical cancer in situ, locally advanced neoplasm, and metastatic neoplasm were excluded from the study. A descriptive and comparative analysis was conducted. Overall survival (OS) and disease-free period were calculated for each histological type with the Kaplan-Meier method and were compared with the log-rank test. RESULTS: A total of 202 records were obtained, of which 131 (64.9%) had SCC, 57 (28.2%) AC, and 14 (6.9%) ASC. The 5-year DFS was 94.4% for SCC, 98.1% for AC, and 92.3% for ASC, without a statistically significant difference (p = 0.55). The 5-year OS for SCC was 97.9%, for AC was 97.8%, and for ASC was 100%, without a statistically significant difference (p = 0.702). CONCLUSIONS: DFS and OS did not differ between the most common histological types of CC at the early stages.

Metaplastic breast cancer: a comparison between the most common histologies with poor immunohistochemistry factors.

BACKGROUND: Metaplastic carcinoma of the breast (MCB) is a rare histological type of breast cancer. This study aimed to determine whether MCB exhibits shorter overall survival (OS) and disease-free survival (DFS) compared with other histologies that are considered unfavorable. METHODS: We retrospectively analyzed 157 clinical file records of the Mexico City-based National Institute of Cancerology and compared the clinical characteristics and treatment of 24 patients with MCB, 37 patients with triple-negative invasive lobular carcinoma (TN-ILC), 48 patients with high-grade invasive ductal carcinoma (HG-IDC), and 48 patients with triple-negative invasive ductal carcinoma (TN-IDC), paired by clinical stage and age. We performed a comparative analysis and analyzed OS and DFS using a log-rank test. RESULTS: In patients with MCB, the 5-year DFS was 52.1% (mean, 48.52 months; 95%: 35.32-61.72), and the 5-year OS was 72.2% (mean, 59.77 months; 95% CI: 48.55-71.00). No differences were observed in the DFS of MCB compared with each of the other histologies (MCB vs. HG-IDC, p = 0.865; MCB vs. TN-IDC, p = 0.966, and MCB vs. TN-ILC, p = 0.132). Moreover, no differences were observed when comparing the OS of MCB with that of each of the other histologies (MCB vs. HG-IDC, p = 0.246; MCB vs. TN-IDC, p = 0.255, and MCB vs. TN-ILC, p = 0.387). CONCLUSIONS: Neither OS nor DFS differ between patients with MCB and those with other histologies with unfavorable immunohistochemical factors.

The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic.

Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis.

Unraveling the genomic landscape of Campylorhynchus wrens along western Ecuador's precipitation gradient: Insights into hybridization, isolation by distance, and isolation by the environment.

Environmental gradients have the potential to influence genetic differentiation among populations ultimately leading to allopatric speciation. However, environmental gradients can also facilitate hybridization between closely related taxa. We investigated a putative hybrid zone in western Ecuador, involving two polytypic wren species (Aves: Troglodytidae), Campylorhynchus zonatus and C. fasciatus. Our study addressed two primary questions: (1) Is there evidence of population structure and genetic admixture between these taxa in western Ecuador? and (2) What are the relative contributions of isolation by distance and isolation by the environment to the observed genetic differentiation along the environmental gradient in this region? We analyzed 4409 single-nucleotide polymorphisms (SNPs) from 112 blood samples sequenced using ddRadSeq and a de novo assembly. The optimum number of genetic clusters ranged from 2 to 4, aligning with geographic origins, known phylogenetics, and physical or ecological constraints. We observed notable transitions in admixture proportions along the environmental gradient in western Ecuador between C. z. brevirostris and the northern and southern genetic clusters of C. f. pallescens. Genetic differentiation between the two C. f. pallescens populations could be attributed to an unreported potential physical barrier in central western Ecuador, where the proximity of the Andes to the coastline restricts lowland habitats, limiting dispersal and gene flow, especially among dry-habitat specialists. The observed admixture in C. f. pallescens suggests that this subspecies may be a hybrid between C. z. brevirostris and C. fasciatus, with varying degrees of admixture in western Ecuador and northwestern Peru. We found evidence of isolation by distance, while isolation by the environment was less pronounced but still significant for annual mean precipitation and precipitation seasonality. This study enhances our understanding of avian population genomics in tropical regions.

Adenocarcinoma metastatic to the uterine cervix: a case series.

AIMS: The objectives of this report are, first, to describe the clinical behavior of cases of carcinoma metastatic to the uterine cervix treated at our institution in order to carry out a systematic review to establish the behavioral patterns of the most frequent metastases to the cervix and, second, to generate guidelines for their diagnosis and treatment. METHODS: At the National Institute of Cancer of Mexico (INCan), we performed a review of the clinical files with a diagnosis of malignant neoplasm metastatic to the uterine cervix between 1990 and 2009. For a systematic review, we conducted a PubMed search between the years 1970 and 2009 of case reports and series of cases of patients with metastatic gastric, breast, ovarian and colorectal cancer. We analyzed each report individually and extracted the patients' clinical data from our cases and reports, including the primary tumor, cervical metastases and survival rates. RESULTS: There were 10 cases of tumors metastatic to the uterine cervix. Metastasis was documented in one-half of the patients during follow up, with two of these cases having the cervix as the only site. We included the following reports in the systematic review: 13 reports of gastric-associated cancer, 30 related to breast cancer, nine with ovarian-associated cancer and 10 related to colorectal cancer. CONCLUSIONS: Metastatic cervical activity is an infrequent event. The prognosis of survival is poor in the presence of gastric or ovarian cancer and cervical metastases.

Lead exposure does not affect baseline and induced innate immunity in quails.

Lead (Pb) is one of the most common metals found in ecosystems in elevated concentrations derived mainly from anthropogenic activities. Pb toxicity is of special concern in birds due to its capacity for bioaccumulation in the liver, bones, and kidneys causing physiological disruptions. Such disruptions can be lethal in a few days after Pb acute intoxication and they are associated with several million deaths of birds. Moreover, Pb may work as an immunosuppressant as it affects the cell-mediated and humoral immune responses, including components of the acute-phase response (APR). We (1) examined the effects of Pb contamination on the innate immune system, body mass, and food intake of Japanese quails (Coturnix coturnix japonica), and (2) evaluated the effects of Pb on its APR after exposing the animals to Pb acetate in drinkable water during 7 days. We found that Pb contamination increased the number of circulating white blood cells (WBCs), but no effect was found on body mass, food intake, the heterophil/lymphocyte (H/L) ratio, and haptoglobin (Hp) concentration. When Pb-exposed birds were injected with lipopolysaccharide from Escherichia coli to activate the APR, they had a negative body mass ratio, reduced food intake, and increased the number of WBCs, the H/L ratio, and the Hp concentration. We conclude that Pb exposure at this dose did not affect baseline values of the constitutive response and that it did not affect the APR of quails, but commend for further studies testing the effect of different Pb doses.

Cancer Genomics.

In the past decade, genomics has fundamentally changed our view of cancer biology, allowing comprehensive analyses of mutations, copy number alterations, structural variants, gene expression and DNA methylation profiles in large-scale studies across different cancer types. Efforts like The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) have fostered international collaborations for cancer genomic analyses and have generated public databases that give scientists around the world access to thoroughly curated data, which have been extensively used as a tool for further hypothesis driven research on several aspects of cancer biology. In parallel, some of these findings are being translated into specific clinical benefits for cancer patients. In this review, we provide a brief historical description of the evolution of international public cancer genome projects and related databases, as well as we discuss about their impact on general cancer research.

microRNA Profile Associated with Positive Lymph Node Metastasis in Early-Stage Cervical Cancer.

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients-one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

Challenges of diagnostic genomics in Latin America.

Cancer genome sequencing methods have now become essential for diagnostic purposes, for devising treatment strategies, and for monitoring disease regression and progression. However, access to these benefits has not permeated homogeneously throughout the world; certain regions, such as Latin America, have been slower at adopting these technologies in terms of their routine use, development and patient access. There are also differences among Latin American subregions with respect to their prioritized types of neoplasia and the drugs that are available and approved in them. An overview of the current situation, including the status of genomics for cancer diagnostics and efforts by type of cancer is presented. In addition, we discuss the perspective of initiatives, alliances, and educational/research programs that pledge to make cancer genomics diagnosis a reality for Latin American individuals' health.