Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population

AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population. METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body. All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients' age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions. RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression. CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population. © 2013 Baishideng.

Avaliação do perfil de metilação e expressão do gene CDH1 em Cebus apella como modelo experimental para câncer gástrico

O câncer gástrico continua sendo uma importante causa de morte dentre os tipos de câncer no Brasil e no mundo. A origem do câncer de estomago provém, assim como nos demais, de acúmulo de alterações genéticas. Portanto, se faz necessário saber quais alterações genéticas são importantes para desencadear a patogênese do câncer gástrico. O MNU, conhecido carcinógeno, quando ingerido de forma oral em doses determinadas desencadeia o desenvolvimento de adenocarcinoma gástrico do tipo intestinal, com aparecimento de estágios pré definidos característico deste tipo tumoral. Com base nestes conhecimentos, realizamos um experimento com 6 macacos da espécie Cebus apella induzidos à desenvolver câncer gástrico do tipo intestinal. Os animais ingeriam 16mg/kg de peso diariamente da droga, com desenvolvimento de lesões pré-neoplásicas em todos. Infelizmente, devido à toxicidade da droga, somente um animal sobreviveu ao tratamento e desenvolveu desenvolveu uma massa tumoral propriamente dita. Foram feitas avaliações periódicas dos animais, em dias pré-determinados (ao início, no 120º, 150º, 300º, 940º) com coletas de fragmentos da mucosa gástrica. Foram coletadas 20 amostras de tecido, distribuídas entre mucosa normal, gastrite, displasia, metaplasia e tumoral. Destas amostras extraímos DNA para as análises do gene CDH1. Não há na literatura sequencia deste gene para a espécie utilizada no estudo. Com este objetivo, utilizamos iniciadores construídos a partir de sequencias de CDH1 de Callithrix jacchus (espécie filogeneticamente) e seqüenciamos cerca de 342pb da região promotora de CDH1 de C. apella. As análises mostraram uma similaridade de 98% desta região com a dos humanos, com presença de vários sítios de ligação de fatores de transcrição (sp1, Ap2, NF-x, AREB6, Puf e CTF) além da presença do CAAT Box. Esta região ainda possui 30 sitios CpGs, o que indica que ela pode estar sofrendo regulação epigenética. Para se verificar como se encontrava o padrão de metilação desta região realizamos uma análise de MSP com iniciadores específicos e constatamos que houve predominância de alelos não metilados de CDH1 para todas as amostras pré neoplásicas e a amostra de adenocarcinoma encontra-se metilada. O que pode ser constatado com um ensaio de Imunohistoquímica, onde somente a amostra tumoral não expressava a proteína caderina. Desta maneira nossas análises sugerem que a metilação do gene CDH1 desempenha papel importante na tumorigênese gástrica em C. apella, e é um evento tardio, uma vez que não é observado nos outro tipos teciduais não tumorais E, partindo-se da similaridade entre as seqüências, podemos sugerir que o mesmo evento pode está ocorrendo em humanos. Esta metilação do promotor do CDH1 leva a um silenciamento deste gene o que desencadeia o estabelecimento de adenocarcinomas gástricos, fato apoiado pela literatura onde vários trabalhos apontaram que a hipermetilação do promotor da caderina está associada ao desenvolvimento do câncer gástrico.

Clinical and pathological importance of vacA allele heterogeneity and cagA status in peptic ulcer disease in patients from North Brazil

We have examined the prevalence of gene cagA and vacA alleles in 129 patients, 69 with gastritis and 60 with peptic ulcer diseases from North Brazil and their relation with histopathological data. vacA and cagA genotype were determined by polymerase chain reaction. Hematoxylin-eosin staining was used for histological diagnosis. 96.6% of the patients were colonized by Helicobacter pylori strains harboring single vacA genotype (nont-mixed infection). Among them, 11.8% had subtype s1a, 67.8% had subtype s1b, and 17% subtype s2. In regard to the middle region analysis, m1 alleles were found in 75.4% and m2 in 21.2% of patients. The cagA gene was detected in 78% patients infected with H. pylori and was associated with the s1-m1 vacA genotype. The H. pylori strains, vacA s1b m1/cagA-positive, were associated with increased risk of peptic ulcer disease and higher amounts of lymphocytic and neutrophilic infiltrates and the presence of intestinal metaplasia. These findings show that cagA and vacA genotyping may have clinical relevance in Brazil.

Expressão dos antígenos ABH e Lewis na gastrite crônica e alterações pré- neoplásica da mucosa gástrica

RACIONAL: A aderência do Helicobacter pylori à mucosa gástrica humana é pré-requisito para sua colonização e o desenvolvimento da gastrite crônica. Os antígenos de grupos sangüíneos, presentes no muco gástrico, são descritos como prováveis receptores da bactéria neste epitélio. A expressão alterada destes antígenos está associada ao desenvolvimento do câncer gástrico. OBJETIVOS: Verificar a ocorrência do Helicobacter pylori e a distribuição da expressão dos antígenos ABH e Lewis correlacionada com as alterações histopatológicas de pacientes com gastrite crônica. PACIENTES E MÉTODOS: Analisaram-se 63 amostras de sangue, saliva e biopsias gástricas de pacientes com gastrite crônica através das técnicas dot-blot-ELISA, imunoperoxidase indireta e colorações do Gram modificado e hematoxilina-eosina. RESULTADOS: Não foram encontradas associações significativas entre a presença da bactéria e os fenótipos de grupos sangüíneos ABH, Lewis e Secretor. Na maioria dos pacientes, a expressão dos antígenos ABH e Lewis, estava restrita principalmente ao epitélio foveolar da mucosa gástrica, concordando com a expressão ao nível salivar. A expressão inapropriada desses antígenos ocorria sempre na infecção pelo Helicobacter pylori e/ou alterações pré-neoplásicas da mucosa gástrica. Em áreas com metaplasia intestinal foi observada a redução da reatividade para os antígenos H e Le^b, e principalmente o aumento de Le^ª. CONCLUSÃO: Alterações no padrão de glicosilação destes antígenos refletem diferentes estágios de diferenciação celular e são marcadores potenciais na avaliação diagnóstica e prognóstica das patologias gástricas.

Protective effect of gamma-tocopherol-enriched diet on N-methyl-N-nitrosourea-induced epithelial dysplasia in rat ventral prostate

Despite recent advances in understanding the biological basis ofprostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been usedto protect against or eradicateprostatemalignancies. Here, we investigated the protective effect of -tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n=8): control (CT): healthy control animals fed a standard diet; control+-tocopherol (CT+T): healthy control animals without intervention fed a -tocopherol-enriched diet (20mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30mg/kg) plus testosterone propionate (100mg/kg) and were fed a standard diet; and MNU+-tocopherol (MNU+T): rats that received the same treatment of MNU plus testosterone and were fed with a -tocopherol-enriched diet (20mg/kg). After 4months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a -tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that -tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate.

Avaliação da integração de esferas de hidroxiapatita sintética e de polietileno poroso em cavidades evisceradas de coelhos

Para a recuperação da estética facial,há necessidade de reposição do volume orbitário perdido em decorrência de eviscerações ou enucleações. Este estudo foi realizado com os objetivos de avaliar comparativamente a biocompatibilidade e a manutenção do volume orbitário com o uso de esferas de hidroxiapatita sintética e de polietileno poroso, na reconstrução de cavidades evisceradas de coelhos. Métodos: Para isso foram utilizados 56 coelhos albinos, submetidos à evisceração do olho direito, com colocação de esferas de hidroxiapatita sintética (G1 – 28 animais) ou polietileno poroso (G2 – 28 animais).Quatro coelhos de cada grupo foram sacrificados em 7 momentos experimentais: 7, 15, 30, 60, 90, 120 e 180 dias após a evisceração. Após o sacrifício, o conteúdo da cavidade orbitária direita foi removido e seccionado na porção central em duas hemi-metades,uma das quais foi preparada para exame histopatológico; exame ultra-estrutural em microscópio eletrônico de varredura foi feito em dois animais de 7, 60 e 180 dias, de ambos os grupos experimentais. Resumo 118 Resultados: Observou-se aos 7 dias, tecido conjuntivo frouxo, constituído de células inflamatórias e hemáceas, em meio à rede de fibrina, principalmente na periferia da esfera de hidroxiapatita e chegando até ao centro da esfera de polietileno; a reação tecidual tornou-se mais densa com o passar do tempo. Decorridos 60 dias, observou-se em G1, início de metaplasia óssea que se acentuou ao longo do experimento. Em todos os momentos experimentais, a inflamação,predominantemente macrofágica, foi muito mais acentuada em G1.O volume da cavidade esclero-corneana foi melhor mantido em G2. Conclusão: a esfera de hidroxiapatita sintética provoca mais inflamação que a de polietileno poroso e é menos eficiente na manutenção do volume orbitário... (Resumo completo, clicar acesso eletrônico abaixo)

Androgen therapy reverses injuries caused by ethanol consumption in the prostate: testosterone as a possible target to ethanol-related disorders

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphology of ileal and jejunal pouches used as rectal substitutes

PURPOSE: Our aim was to determine whether the mucosa of a canine jejunal pouch used as a rectal substitute after proctocolectomy retains its morphologic features better than the mucosa of a canine ileal pouch so used. METHODS: Among ten dogs that underwent proctocolectomy, five had a jejunal pouch-distal rectal anastomosis and five an ileal pouch-distal rectal anastomosis. After six months, the animals were killed, the intestinal pouches and portions of unaltered distal ileum were removed, and a blinded, mucosal morphometric analysis was performed. RESULTS: The mucosa of the jejunal pouches had an overall thickness (mean ± standard deviation, anterior and posterior walls, 1,300 ± 140 μm), villous height (286 ± 46 μm), and crypt depth (790 ± 77 μm) greater than that of the ileal pouches (920 ± 170, 208 ± 47, and 530 ± 130 μm, respectively; P < 0.05). Moreover, the mucosal thickness of the jejunal pouches was similar to that of the distal ileum proximal to the pouch (1,200 ± 200 μm; P > 0.05), whereas the mucosal thickness of the ileal pouch was thinner (P < 0.05). CONCLUSIONS: The jejunal mucosa retains its major morphometric features when the jejunum is used as a rectal substitute after proctocolectomy. In contrast, the ileal mucosa atrophies when the ileum is so used.

Gastric and small intestinal lesions after partial stomach resection with Billroth II or Roux-en-Y reconstruction in the rat

The evolution and phenotypic expression of mucosal lesions of the gastric stump were investigated in male rats submitted to gastric resection with reconstruction by the Billroth II technique (BII with biliopancreatic reflux, BPR) or by the Roux-en-Y procedure (without BPR). Animals were studied at 24, 36, 54 and 64 weeks after surgery and the phenotypic expression of lesions analysed using routine hematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff (GOS) and sialidase GOS reactions). BPR was found to be responsible for the formation of adenomatous hyperplasia (AH), increasing in incidence and size with time, since the Roux-en-Y procedure failed to induce the gastric stump lesions observed after BII reconstruction. AHs always occurred in the transition of the gastrojejunal junction, a site offering special conditions for BPR influence, and were classified as gastric (G), intestinal (I) and G+I types according to their phenotypic expression. No pure I type AH was diagnosed at any time point. The G and G+I types developed at approximately equal incidences (i.e., G type 7/17, G+I type 10/17 at the 64th week). It was suggested that both gastric and intestinal mucosal elements were stimulated to proliferate by BPR, with the gastric mucosa tending to demonstrate AH. Intestinal type components of AH were found adjacent to the jejunum and not at the stomach margin, indicating an origin from intestinal mucosa. No metaplasia of the gastric mucosa was observed in any animal after partial gastric resection. In 101 rats submitted to the BII procedure, 5 mucinous adenocarcinomas were eventually diagnosed, mostly located in the subserosa of the gastrojejunal junction. All carcinomas expressed the phenotype of cells of the small intestine. Evidence of malignant transformation within the gastric components of AH was not observed even at the 64th week. In conclusion, all lesions induced by BPR in the rat remnant stomach are benign, and the few true cancers that arise in association are derived from the small intestine.

Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol

In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Immunohistochemical Analysis of Human Homologue of Drosophila Patched (PTCH) in Dental Follicles of Impacted Third Molars

This study investigated the immunodetection of PTCH in epithelial components of dental follicles associated with impacted third molars without radiographic signs of pathosis. One hundred and five specimens of dental follicles associated with impacted third molars with incomplete rhizogenesis (between Nolla's stage 6 and 9) were surgically removed from 56 patients. Epithelial cell proliferation was determined by using immunohistochemical labeling. Statistical analysis was performed using Fisher exact test and a level of significance of 5%. Of the 105 dental follicles collected, 3 were PTCH-positive. The specimens with squamous metaplasia and epithelial hyperplasia had higher rates of positivity for PTCH, as well as those with active remnants of odontogenic epithelium. This study suggests that the odontogenic cells of the dental follicle might be proliferating during the rhizogenesis, while the squamous metaplasia and hyperplasia of the epithelial lining and proliferative odontogenic epithelial rests show the differentiation potential of dental follicles.

Differential Proteomic Analysis of Noncardia Gastric Cancer from Individuals of Northern Brazil

Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study sets.

Squamous Cell Carcinoma of Mammary Gland in Domestic Cat

Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years before, but with previous administration of contraceptives. At the physical examination, it was observed ulcer between the caudal abdominal mammary glands. The occurrence of skin or mammary neoplasia was conceived. The following complementary tests were requested: complete blood count, serum biochemical profile (renal and hepatic), chest radiographs, abdominal ultrasound, and incisional biopsy of the ulcerated region periphery, followed by classic histopathology. The lesion histopathology was compatible with squamous cell carcinoma of the mammary gland. Due to such a diagnosis, bilateral mastectomy was recommended. The material obtained during the surgical procedure was sent for anatomopathological analysis. Microscopically, surgical margins infiltration and a regional lymph node were verified. The owner was advised of the need for complementary therapies and medical monitoring of the cat. However, there was no return. It is noteworthy that the animal's physical and laboratory examinations showed no neoplasia in other regions, being the squamous cell carcinoma of the mammary gland considered primary. Discussion: The malignant mammary neoplasia genesis in feline species, in general, seems to be related to steroid hormones. The ovariectomized females are less likely to develop the disease when compared to intact cats, but there is no protective effect of surgery on those spayed after two years of age regarding the appearance of the neoplasia. Thus, at the time the reported patient was ovariectomized, this effect no longer occurred. The synthetic progestins regularly used to prevent estrus increase by three times the risk of breast carcinomas onset. In humans, there is no clear definition of the etiology and pathogenesis of mammary squamous cell carcinoma. However, it has been suggested its association with extreme forms of squamous metaplasia present in pre-existing mammary adenocarcinoma, besides cysts, chronic inflammations, abscesses and mammary gland adenofibromas. In a hypothetical way, this etiology could also be related to the feline mammary carcinoma, although, for the case at issue, the exogenous and endogenous hormonal influence should not be excluded. It has been reported that mammary squamous cell carcinomas in cats are classified in grades II and III (ie, moderately and poorly differentiated, respectively). Thus, they are considered tumors with more unfavorable prognosis. However, the monitoring of the clinical course, in order to evaluate possible recurrence of the neoplasia and metastases to distant sites, was not possible as the animal under discussion did not return. The squamous cell carcinoma is the most common skin tumor in feline species, despite the primary location in the mammary gland. It is, therefore, important to differentiate squamous cell carcinoma originated in the breast from histological types derived from skin. The description of this special and rare feline mammary carcinoma is important due to its particular characteristics and potential for malignancy.

Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles

Purpose: Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. Methods: To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT-PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). Results: Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. Conclusions: These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease.

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

Background: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34(+) hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. Results: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34(+) cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34(+) cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.