Description of Genetic Variants in BRCA Genes in Mexican Patients with Ovarian Cancer: A First Step towards Implementing Personalized Medicine.

Gynecologic cancers are among the leading causes of death worldwide, ovarian cancer being the one with the highest mortality rate. Olaparib is a targeted therapy used in patients presenting mutations in BRCA1 and BRCA2 genes. The aim of this study was to describe BRCA1 and BRCA2 gene variants in Mexican patients with ovarian cancer. Sequencing of BRCA1 and BRCA2 genes from tumors of 50 Mexican patients with ovarian cancer was made in a retrospective, non-randomized, and exploratory study. We found genetic variants in 48 of 50 cases. A total of 76 polymorphic variants were found in BRCA1, of which 50 (66%) had not been previously reported. Furthermore, 104 polymorphic variants were found in BRCA2, of which 63 (60%) had not been reported previously. Of these polymorphisms, 5/76 (6.6%) and 4/104 (3.8%) were classified as pathogenic in BRCA1 and BRCA2, respectively. We have described the genetic variants in BRCA1 and BRCA2 of tumors from Northeast Mexican patients with sporadic ovarian cancers. Our results showed that the use of genetic testing helps recognize patients that carry pathogenic variants which could be beneficial for personalized medicine treatments.

A New Gene Expression Signature for Triple Negative Breast Cancer Using Frozen Fresh Tissue before Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer tumors. Comparisons between TNBC and non-triple negative breast cancer (nTNBC) may help to differentiate key components involved in TNBC neoplasms. The purpose of the study was to analyze the expression profile of TNBC versus nTNBC tumors in a homogeneous population from northeastern Mexico. A prospective study of 50 patients was conducted (25 TNBC and 25 nTNBC). Clinic parameters were equally distributed for TNBC and nTNBC: age at diagnosis (51 vs 47 years, p=0.1), glucose levels (107 mg/dl vs 104 mg/dl, p=0.64), and body mass index (28 vs 29, p=0.14), respectively. Core biopsies were collected for histopathological diagnosis and gene expression analyses. Total RNA was isolated and expression profiling was performed. 40 genes showed differential expression pattern in TNBC tumors. Among these, 9 over-expressed genes (PRKX/PRKY, UGT8, HMGA1, LPIN1, HAPLN3, and ANKRD11), and one under-expressed (ANX9) gene are involved in general metabolism. Based on this biochemical peculiarity, and the over-expression of BCL11A and FOXC1 (involved in tumor growth and metastasis, respectively) we validated by qPCR the expression profile of 7 genes out of the signature. In this report, a new gene signature for TNBC is proposed. To our knowledge, this is the first TNBC signature which describes genes involved in general metabolism. The findings may be pertinent for Mexican patients and require to be evaluated in further ethnic groups and populations.

Myocardial ischemia as presenting manifestation of IgG4-related disease: a case-based review.

Coronary involvement in IgG4-related disease (IgG4-RD) has been scarcely reported, and myocardial ischemia as its presenting feature is even rarer. Here, we describe an additional case with novel and relevant observations. The patient was a previously healthy, middle-aged woman who presented to the clinic with new-onset typical angina. One tumefactive lesion encasing the left anterior descending artery was found during her workup. The most common underlying malignancies with secondary cardiac involvement were rationally ruled out. Symptoms persisted despite medical treatment, and she was therefore referred to surgery. Tumor excision was successfully performed, and she received coronary bypass grafting. IgG4-related coronary arteritis with pseudotumor formation was subsequently diagnosed following the comprehensive diagnostic criteria. This condition was clinically classified as active and circulating plasmablasts were found to be increased (5480/mL), even when these were determined 38 days after surgery. A PET/CT revealed an additional hypermetabolic lymph node. She was therefore treated with rituximab as induction therapy (two 1000 mg doses, administered 15 days apart). Three months later, her disease remained clinically inactive. Circulating plasmablasts were repeated and these had dropped to 0/mL. We thereafter review the current and pertinent literature on the topic, emphasizing the previous cases with similar presenting features (n = 7). We lastly suggest that IgG4-RD should be part of the differential diagnosis of any patient with tumefactive lesions surrounding the coronary arteries, since it can initially presented as sudden cardiac death.

Demyelinating pseudotumor.

Demyelinating disease presenting as a solitary contrast-enhancing mass poses a diagnostic challenge for both radiologists and surgical pathologists. We report the cases of two female patients, aged 23 and 37 years, who exhibited the clinical and radiologic features of a space-occupying mass strongly suggestive of neoplasia. In both patients, magnetic resonance imaging showed a ring-enhancing parietal lesion. Intraoperative frozen sections in both patients displayed histologic features strongly suggestive of a glial neoplasm, including marked hypercellularity, a prominent astrocytic component, and easily identifiable mitotic figures. However, permanent sections showed additional and helpful histologic findings that included Creutzfeldt astrocytes and granular mitoses. Subsequent immunostaining showed that the hypercellularity was principally caused by macrophage infiltration (HAM-56 and CD68) and an associated reactive astrocytosis (glial fibrillary acidic protein). Additional confirmatory tests included special stains for myelin (Luxol-fast-blue), which demonstrated focal, sharply marginated loss of myelin, and for axons (silver stain for axons and neurofilament protein immunohistochemistry), which showed relative preservation of axons in areas of myelin loss. Together, the special stains confirmed the demyelinating nature of the lesions. The keys to avoiding misdiagnosing a demyelinating pseudotumor as a diffuse glioma include a general awareness of this potential pitfall, including the radiologic appearance of demyelinating pseudotumors as contrast-enhancing solitary masses that mimic tumor; knowledge of the characteristic histologic features, including Creutzfeldt astrocytes and granular mitoses; and a high index of suspicion for macrophage infiltration combined with a willingness to use appropriate confirmatory immunohistochemical studies in suspicious or uncertain cases. This approach will minimize the chance of misdiagnosis and subsequent use of inappropriate and deleterious therapies.

Linfoma indiferenciado tipo Burkitt, primario, en ovario y embarazo / Undifferentiated lymphoma, Burkitt Type, primary, in the ovary and pregnancy

Se presenta el caso de una mujer de 23 años de edad, con embarazo de 30 semanas y crecimiento rápido y progresivo del perímetro abdominal, así como disnea importante. Los estudios diagnósticos demostraron producto único vivo intrauterino, ascitis y una masa heterogénea en hipocondrio izquierdo a expensas del anexo; un registro cardiotocográfico mostró sufrimiento fetal agudo; se practicó cesárea de urgencia e histerosalpingoooforectomía bilateral y omentectomía; el diagnóstico final fue de linfoma indiferenciado tipo Burkitt en ovario. La literatura revisada incluye 26 casos previos de linfoma no Hodgkin y embarazo; éste es el primero en que el tipo de linfoma corresponde a un Burkitt (indiferenciado de Rappaport o de células pequeñas no hendiadas de Luke) localizado en ovario y primario