ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women.

BACKGROUND: Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. METHODS: DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy-Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. RESULTS: We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13-3.51, TT vs. GG; OR, 1.53; 95% CI 1.12-2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. CONCLUSIONS: Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

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.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon).

BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee.

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

CDX-2, MUC-2 and B-catenin as intestinal markers in pure mucinous carcinoma of the breast.

BACKGROUND: Pure mucinous adenocarcinoma of the breast is a rare entity characterized by the production of variable amounts of mucin comprising 1% to 6% of breast carcinomas. Some mucinous adenocarcinomas have shown expression of intestinal differentiation markers such as MUC-2. This study examines the expression of intestinal differentiation markers in this type of breast carcinoma. RESULTS: Twenty-two cases of pure mucinous adenocarcinoma of the breast were assessed. Immunochemistry was performed for beta-catenin, CDX-2 and MUC-2. All cases were positive for B-catenin. MUC-2 positivity was observed in all cases; 63. 6% were 3 plus positive. All cases were negative for CDX-2. CONCLUSIONS: These results suggest that mucinous breast carcinomas express some markers of intestinal differentiation, such as MUC-2 and beta-catenin; however, future studies with a larger series of cases and using molecular techniques that help affirm these results are needed.

Intestinal-type adenocarcinoma arising from a villous adenoma in the renal pelvis in the context of a kidney abscess: Case report.

Villous adenoma is a benign neoplasm with an exceptional presentation in the renal pelvis, hence very few cases have been reported. Herein we present the case of a patient who presented with left flank pain clinically suggestive of complicated pyelonephritis, culminating in simple nephrectomy with a villous adenoma in the renal pelvis as histopathological finding associated to the presence of a microscopic focus of intestinal-type adenocarcinoma.

[The imprint cytology: a tool diagnosis in the operating room]. / Impronta citológica: herramienta en el diagnóstico transoperatorio.

BACKGROUND: since 1929, the imprint cytology has a great value in the transoperatory as a diagnostic tool and in some cases as an alternate method. METHODS: during two years period, 416 transoperatory specimens and 384 frozen sections were performed in the Pathology and Cytopathology Department of the University Hospital, "Dr. José E. Gonzalez." Diagnoses were recorded and compared both methods with the final diagnosis given at definitive histological sections. The results were evaluated and p statistics were performed. RESULTS: nine of 416 patients (2.2 %) were incorrectly diagnosed by cytology, and 8 of 384 (2.1 %) by frozen section. The diagnostic accuracy for the imprint cytology was 97.8 % and 97.9 % for frozen section. Six of the 416 cases (1.4 %) were misdiagnosed by imprints and frozen sections; the percentage success was 98.5 % using both methods together. The p was statistically significant (0.0005). CONCLUSIONS: the transoperatory cytology is a fast, easy and inexpensive. It provides morphological detail on intact cells and without the freezing artifacts, so its use as an adjunct to the frozen method is of great value.

Metastatic Penile Adenocarcinoma in the Context of Rectal Cancer.

The presence of penile metastatic lesions proceeding from primary rectal tumors is a rare entity usually associated with a poor prognosis. Clinical presentation and localization may vary. There exists no consensus gold standard treatment for penile metastatic lesions, and there is continuous debate on whether lesions should undergo surgical, chemotherapeutic or palliative management.

Identification of viral infections in the prostate and evaluation of their association with cancer.

BACKGROUND: Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. METHODS: 130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. RESULTS: R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. CONCLUSIONS: We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

Diagnosis of carcinosarcoma metastatic to the umbilicus by fine needle aspiration biopsy: a case report.

BACKGROUND: Metastasis to the umbilicus, known as Sister Mary Joseph's nodule, sometimes represents the first clinical manifestation of an internal malignancy. These nodules are infrequent, and their discovery has prognostic implications. CASE: An 86-year-old woman presented with an ultrasound diagnosis of peritoneal carcinomatosis and the presence of a round lesion in the umbilical area. A fine needle aspiration biopsy was performed. The cytologic smears showed a biphasic neoplasm composed of malignant epithelial cells with a glandular appearance and randomly scattered spindle cells in a necrotic base. Immunohistochemical staining was performed to confirm the diagnosis. CONCLUSION: After an extensive search of the literature, we discovered that this is the first report of a metastatic carcinosarcoma diagnosed by fine needle aspiration biopsy. The diagnosis of carcinosarcoma requires a clear definition of the 2 components, which is why immunohistochemical staining is very useful. The presence of an umbilical nodule should raise suspicion of an underlying malignant neoplasm. Needle aspiration biopsy should be considered as the most effective, simple, uncomplicated method of diagnosing these lesions.

[Ovarian ginandroblastoma as a transcesarean incidental finding. A case report and literature review]. / Ginandroblastoma de ovario como hallazgo transcesárea. Reporte de un caso y revisión de la bibliografía.

The gynandroblastoma is an extremely rare sexual cord stromal tumor, which contains both male and female elements, characterized by Sertoli or Leydig cells and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old female patient, found accidentally during a cesarean section operation. There is only one reported case in world literature occurring in a pregnant woman. The principal component we found was adult granulose cells, with a microfollicular pattern, and the presence of luteinized cells in some areas; besides we found the presence of well differentiated Sertoli cells elements, in addition to Leydig cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings were performed: citokeratin, which resulted positive in Sertoli cells and negative in granulose cells; and inhibin, which was positive in both components showing its mixed origin.

Clinical stage I synchronous bilateral testicular germ cell tumor with different histopathology: a case report.

Bilateral testicular germ cell tumors (BTGCT) occur in 1 to 4% of patients with testicular cancer and of these, 10-15% are synchronous. Overall, BTGCT represents less than 0.5% of all new cases of testicular cancer. There are few reports in the literature of synchronous BTGCT with different histology. We present the case of a 30-year-old man who presented to our genitourinary tumor unit with a bilateral increase of testicular volume. After initial assessment, a testicular ultrasound showed the presence of solid tumors in both testes. Staging studies were negative for metastatic disease. The patient was referred to the fertility clinic for sperm banking and later underwent a bilateral radical orchiectomy. The histopathology evaluation revealed a 5.5 cm right-sided mixed germ cell tumor and a 1.5 cm left-sided testicular seminoma. Because patient's poor compliance for surveillance was identified as a risk factor for relapse and poor outcome, adjuvant chemotherapy was favored. The patient underwent one cycle of bleomycin, etoposide and cisplatin (BEP). After four years of follow up, the patient shows no evidence of relapse, either clinically or radiologically. In men unlikely to carry out successful surveillance; active treatment is the preferred option for preventing disease recurrence, even in patients with no risk factors. The physician must consider all available therapeutic measures in this scenario to achieve the best possible therapeutic result.

Tumor of the epididymis: an uncommon presentation of disseminated coccidioidomycosis.

Coccidioidomycosis is an endemic disease of arid regions in the Western hemisphere. Its clinical presentation varies from asymptomatic nodules on chest x-rays to disseminated disease. We present the case of a 48-year-old man with a hard and heterogeneous tumor in the posterior aspect of the right testis. Color flow doppler testicular ultrasonography was performed and two nodular masses in the tail of the right epididymis were identified. An epididymectomy was performed and histopathological examination revealed coccidioidomycosis. After diagnosis, the patient was successfully treated with fluconazol.

Steroid 5 alpha-reductase 2 enzyme variants, biomass exposure and tobacco use in Mexican patients with prostate cancer.

The presence of the genetic variants of the steroid 5-alpha reductase 2 enzyme, which is encoded by the SRD5A2 gene, has been associated with an increased risk of developing prostate cancer among certain ethnic groups. However, these molecular studies have not been conducted on the Mexican population. The analysis of the genetic variants, rs9282858 and rs523349, was performed in 101 males with prostate cancer and 100 healthy controls classified as males without prostate abnormalities (n=60) and males with benign prostatic hyperplasia (n=40), to identify a probable association with this cancer type in the Northeast Mexican population. An association was identified between prostate cancer and biomass exposure [P=0.012; odds ratio (OR), 2.89; confidence interval (CI)=1.21-6.88] and tobacco use (P=0.028; OR=1.88; CI=1.07-3.31), while no association was observed between cancer development and the rs9282858 variant, or between a protective effect and the rs523349 variant. Notably, an association was identified between rs523349 and biomass exposure (P=0.013, OR=3.17; CI=1.23-8.17 for the G risk allele, and OR=0.32, CI=0.12-0.81 for the C protective allele) using the dominant genetic model. To the best of our knowledge, the present study was the first of its type to investigate the Mexican population with prostate cancer.

Non-syndromic bilateral ovarian sex cord stromal tumor with annular tubules in a postmenopausal elderly woman as an incidental finding.

INTRODUCTION: Sex cord tumors with annular tubules (SCTAT) are very rare neoplasms comprising less than 1% of sex cord ovarian tumors. They usually occur in women of reproductive age and tend to be associated with Peutz Jeghers Syndrome (PJS), be bilateral, multifocal, and small. When diagnosed in older patients they are often described as sporadic, unilateral, predominantly cystic and bigger. CASE PRESENTATION: A bilateral hysterosalpingo-oophorectomy was performed in a seventy-one year-old-woman with postmenopausal bleeding showing no features of PJS. A bilateral SCTAT was diagnosed, associated with a focus of Leydig cell hyperplasia, an endometrial polyp and endomethroid intraepithelial neoplasia. DISCUSSION: SCTAT is a very rare histological variant in postmenopausal women. The case we present is special, different to what has been reported in the literature regarding these tumors. CONCLUSION: It is important to be aware that SCTATs can also be present in older women, they can be bilateral despite not being related to PJS syndrome and must be considered as a differential diagnosis in ovarian tumors.

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases.

BACKGROUND: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. METHODS: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). RESULTS: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores > or = 7. CONCLUSION: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason > or = 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns.

Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes.

BACKGROUND: Male EBP disorder with neurologic defects (MEND) syndrome is an X-linked disease caused by hypomorphic mutations in the EBP (emopamil-binding protein) gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation. METHODS: We studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole-exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in-house scoring system. RESULTS: Twenty-seven from 105 missense variants found in 45 genes of the four exomes were considered significant (-5 to -9 scores). We found a direct genotype-phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants. CONCLUSION: We conclude that APOA5 (rs3135506), ABCA1 (rs9282541), and APOB (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.

Genetic alterations of triple negative breast cancer (TNBC) in women from Northeastern Mexico.

Triple negative breast cancer (TNBC) is a subtype of breast cancer of heterogeneous nature that is negative for estrogen receptor (ER), progesterone receptor (PR) and growth factor human epidermal 2 (HER2) following immunohistochemical analysis. TNBC is frequently characterized by relapse and reduced survival. To date, there is no targeted therapy for this type of cancer. Chemotherapy, radiotherapy, and surgery remain as the standard treatments options. The lack of a target therapy and the heterogeneity of TNBC highlight the need to seek new therapeutic options. In this study, fresh tissue samples of TNBC were analyzed with a panel of 48 driver genes (212 amplicons) that are likely to be therapeutic targets. We found intron variants, missense, stop gained and splicing variants in TP53, PIK3CA and FLT3 genes. Interestingly, all the analyzed samples had at least two variants in the TP53 gene, one being a drug response variant, rs1042522, found in 94% of our samples. We also found seven additional variants not previously reported in the TP53 gene, to the best of our knowledge, with probable deleterious characteristics of the tumor suppressor gene. We found four genetic variants in the PIK3CA gene, including two missense variants. The rs2491231 variant in the FLT3 gene was identified in 84% (16/19) of the samples, which not yet reported for TNBC, to the best of our knowledge. In conclusion, genetic variants in TP53 were found in all TNBC tumors, with rs1042522 being the most frequent (94% of TNBC biopsies), which had not been previously reported in TNBC. Also, we found two missense variants in the PIK3CA gene. These results justify the validation of these genetic variants in a large cohort, as well as the extensive study of their impact on the prognosis and therapy management of TBNC.

A 5-year-old girl with a congenital ganglioneuroma diagnosed by fine needle aspiration biopsy: a case report.

INTRODUCTION: Ganglioneuroma is a rare, benign, neuroblastic tumor arising mainly from the central or peripheral autonomic nervous system, especially the sympathetic system. The most affected anatomical sites are the posterior mediastinum, retroperitoneum, adrenal gland and head and neck soft tissue. In the current literature, reports of ganglioneuroma diagnosed by fine-needle aspiration and its cytological appearance are scarce. CASE PRESENTATION: A 5-year-old girl presented with a mass in the cervical region since birth. Laboratory routine tests were within normal limits, ultrasonography demonstrated a solid and well-circumscribed lesion in the soft tissues of the cervical region. Fine needle aspiration biopsy was carried out, and the obtained smears showed a mixture of mature ganglion cells and groups of spindle cells suggestive of schwann cell origin. A diagnosis of ganglioneuroma was suggested. Core biopsy and surgical resection confirmed this diagnosis. CONCLUSION: Congenital ganglioneuroma of the cervical region is an uncommon soft tissue benign neoplasm of neuroblastic origin, and it should be considered in the differential diagnosis of head and neck pediatric soft tissue tumors. Fine needle aspiration biopsy technique is a reliable method that can be used with confidence when dealing with pediatric soft tissue tumors.

Microsatellite instability and protein expression of MLH1 and MSH2 genes in young Mexican patients less than 50 years of age diagnosed with colorectal cancer.

Diagnosis of colorectal cancer in patients under 45 years old should alert us to possible hereditary forms of this neoplasia. Most cases of hereditary colorectal cancer correspond to Lynch syndrome which is caused by mutations in DNA mismatch repair genes, particularly MLH1 and MSH2. The dysfunction is associated with microsatellite instability which occurs in 95% cases of this syndrome and in 15% of sporadic colorectal cancer. In sporadic colon tumors, downregulation of MLH1 is observed in cases with the BRAF V600E variant, which induces hypermetylation of the MLH1 promoter. Mutation screening for hereditary cancer has impacted the diagnosis, genetic counseling, and early tumor detection in families affected by hereditary colorectal cancer syndromes but mutation screening technologies are seldom available in public health care centers in developing countries. This study aimed to describe immunohistochemistry and microsatellite instability abnormalities in tumor samples archived in a public hospital in Mexico. Paraffin-embedded samples of patients with colorectal cancer, diagnosed at under 50 years old, were studied to analyze correlations among clinical variables, MLH1 and MSH2 protein expression (immunohistochemistry), microsatellite instability (fluorescent PCR-based assay), and BRAF V600E variant (real time PCR). Forty-seven tumor specimens from patients with TNM stage II and above were analyzed. Tumors were mainly located in the proximal colon segment and displayed histologic intestinal variety and infiltration to serosa. Twenty samples showed decreased expression of mismatch repair proteins and 10 of these presented microsatellite instability (7 high and 3 low instability patterns, respectively). There were no instances of BRAF V600E mutation found. Altered MLH1 or MSH2 expression was found in 42.5% of the samples and microsatellite instability was observed in 21.3% of the tumors. These results suggested that about a fifth of the patients were candidates for family assessment and genetic counseling.