Publications by authors named "Denise Peixoto Guimarães"

25 Publications

  • Page 1 of 1

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

Pathobiology 2021 Oct 12:1-9. Epub 2021 Oct 12.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC).

Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals.

Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology.

Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics.

Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518697DOI Listing
October 2021

The Automatically Analyzed (AA) ColonView (CV) Quick Test for Fecal Occult Blood Shows Higher Diagnostic Accuracy in Detection of Colorectal Adenoma than Visually Analyzed Tests.

Anticancer Res 2021 Nov;41(11):5517-5525

Department of Surgery, Kuopio University Hospital and School of Medicine, University of Eastern Finland, Kuopio, Finland;

Background/aim: The present study compared the accuracy of visually analyzed (VA) and automatically analyzed (AA) ColonView (CV) quick test; a new-generation fecal immunochemical test (FIT) for hemoglobin (Hb) and hemoglobin/haptoglobin (Hb/Hp) (Biohit Oyj, Helsinki, Finland) in subjects participating in colorectal neoplasia (CRN) detection in Brazil. A traditional guaiac-based fecal occult blood test (gFOBT) test (HemoccultSENSA) was used as a reference.

Patients And Methods: A cohort of 509 colonoscopy-referral patients were asked to collect three consecutive fecal samples, to be analyzed by both CV and SENSA.

Results: In ROC analysis for the AA reading, the optimal cut-off value for CV Hb was ≥8.0912 and that for CV Hb/Hp was ≥1.8983. With these cut-offs, the sensitivity (Se), specificity (Sp), and efficiency of CV AA in detecting colorectal adenoma (CRA) were: 64.2%/78.6%, 53.4%/35.3%, and 58.6%/56.5%, for Hb and Hb/Hp, respectively. In the HSROC analysis, the AUC values for i) VA and ii) AA modes were as follows: i) AUC=0.551 (95%CI=0.500-0.602), ii) AUC=0.606 (95%CI=0.550-0.662). The difference between these AUC values was statistically significant (p=0.0160).

Conclusion: The present study confirms the previous results on the applicability of the ColonView quick test in CRN screening. Of the two optional reading modes, the AA reading showed significantly better diagnostic accuracy as compared to the VA reading (or SENSA), in detecting the CRA endpoint in colonoscopy-referral patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15365DOI Listing
November 2021

Profile of esophageal squamous cell carcinoma mutations in Brazilian patients.

Sci Rep 2021 Oct 18;11(1):20596. Epub 2021 Oct 18.

Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela, 1331, Barretos, São Paulo, 14784 400, Brazil.

Esophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 (7/46, 15.2%), NFE2L2 (5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients' clinicopathological features. Applying an evolutionary action score of p53 (EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-00208-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523676PMC
October 2021

The New Generation Immunochemical Test for Fecal Occult Blood (ColonView Quick Test) Shows a High Diagnostic Accuracy in Colorectal Cancer Detection.

Anticancer Res 2021 Oct;41(10):5071-5079

Department of Surgery, Kuopio University Hospital and School of Medicine, University of Eastern Finland, Kuopio, Finland;

Background/aim: The present study compared the accuracy of visually analyzed (VA) and automatically analyzed (AA) ColonView (CV) quick test; a new-generation immunochemical test (FIT) for Hb and Hb/Hp (Biohit Oyj, Helsinki, Finland) in subjects participating in colorectal cancer (CRC) detection in Brazil. A traditional gFOBT test (HemoccultSENSA) was used as a reference.

Patients And Methods: A cohort of 368 colonoscopy-referral patients were asked to collect 3 consecutive fecal samples, to be analysed by both assays (CV, SENSA).

Results: In receiver operating characteristic (ROC) analysis for the AA reading, the optimal cut-off value for CV Hb AA (test AA 3) was ≥117 and that for CV Hb/Hp AA (test AA 4) was ≥48. In the hierarchical summary receiver operating characteristic (HSROC) analysis for pooled accuracy of CV with AA and VA reading, the AUC values for i) VA and ii) AA were as follows: i) AUC=0.859 (95%CI=0.839-0.879), ii) AUC=0.931 (95%CI=0.920-0.942). The difference between these AUC values (Roccomp analysis) was statistically significant (p=0.0024).

Conclusion: The present study confirms the previous studies on the applicability of the ColonView quick test (a new-generation FIT) in CRC screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15323DOI Listing
October 2021

Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening.

Scand J Gastroenterol 2021 Aug 3;56(8):920-928. Epub 2021 Jul 3.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Aims: Epigenetic alterations of genes involved in colorectal carcinogenesis are likely to be informative biomarkers for early detection. We assessed the methylation profile of a panel of seven colon cancer-related genes comparing normal colon, colorectal cancer (CRC) precursor lesions and cancer tissues from a Brazilian cohort.

Methods: The cohort comprised 114 CRC patients, including 40 matched normal tissue, 47 patients with adenomas, 33 with serrated polyps and 8 with normal colonic biopsy. DNA methylation status of , , , , , and was determined by pyrosequencing and correlated with clinicopathological features. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for all genes using cancer endpoint.

Results: The most frequently methylated genes in cancer and in precancer lesions were , , and , ranging from 55.3 to 95% of the samples. Overall, the frequency of methylation of these four genes in normal colonic tissue was significantly lower as compared to cancer or precursor lesions both in adenoma-carcinoma ( < .001 and  < .050) and serrated (sessile-serrated lesion) ( < .001 and  < .050) pathways. Additionally, sensitivity for the cancer endpoint ranged from 65.6 to 91.8%, and specificity from 17.9 to 62.9% for , , , and genes. Moreover, the comethylation of ≥4 genes was higher in sessile-serrated lesion (87.5%) and conventional adenomas (78.7%) than in hyperplastic polyps (43.7%) ( = .025) and was significantly associated with proximal cancers ( = .042).

Conclusions: Our study suggests the DNA methylation can constitute potential biomarkers in CRC screening of Brazilian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00365521.2021.1922744DOI Listing
August 2021

Pyknon-Containing Transcripts Are Downregulated in Colorectal Cancer Tumors, and Loss of Is Associated With Worse Patient Outcome.

Front Genet 2020 12;11:581454. Epub 2020 Nov 12.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Pyknons are specific human/primate-specific DNA motifs at least 16 nucleotides long that are repeated in blocks in intergenic and intronic regions of the genome and can be located in a new class of non-coding RNAs of variable length. Recent studies reported that pyknon deregulation could be involved in the carcinogenesis process, including colorectal cancer. We evaluated the expression profile of a set of 12 pyknons in a set of molecularly characterized colorectal cancer (CRC) patients. The pyknons (, , , , , , , , , , , and ) expression was determined by qRT-PCR. A pilot analysis of 20 cases was performed, and consistent results were obtained for , , , , and . Further, the expression of the selected pyknons was evaluated in 73 CRC cases. Moreover, in 52 patients, we compared the expression profile in both tumor and normal tissues. All five pyknons analyzed showed significantly lower expression levels in the tumor compared to normal tissue. It was observed an association between expression of with mutations ( = 0.029), to histologic grade ( = 0.035), and to clinical staging ( = 0.016). Moreover, levels of were significantly associated with the patient's poor overall survival ( = 0.04). We reported the significant downregulation of pyknons motifs in tumor tissue compared with the normal counterpart, and the association of lower expression with worse patient outcome. Further studies are needed to extend and validate these findings and determine the clinical-pathological impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.581454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693444PMC
November 2020

The Role of Fusobacterium nucleatum in Colorectal Carcinogenesis.

Pathobiology 2021 8;88(2):127-140. Epub 2020 Dec 8.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil,

Colorectal cancer (CRC) is one of the most frequent and deadly neoplasms worldwide. Genetic factors, lifestyle habits, and inflammation are important risk factors associated with CRC development. In recent years, growing evidence has supporting the significant role of the intestinal microbiome in CRC carcinogenesis. Disturbances in the healthy microbial balance, known as dysbiosis, are frequently observed in these patients. Pathogenic microorganisms that induce intestinal dysbiosis have become an important target to determine the role of bacterial infection in tumorigenesis. Interestingly, the presence of different bacterial strains, such as Fusobacterium nucleatum, has been detected in tissue and stool from patients with CRC and associated with substantial clinical and molecular features, as well as with patient therapy response. Therefore, understanding how the presence and levels of F. nucleatumstrains in the gut affect the risk of CRC onset and progression may inform suitable candidates for interventions focused on modulation of this bacteria. Here we review new insights into the role of gut microbiota in CRC carcinogenesis and the clinical utility of using the detection of F. nucleatum in different settings such as screening, prognosis, and microbiota modulation as a means to prevent cancer, augment therapies, and reduce adverse effects of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512175DOI Listing
December 2020

The Performance of Colorectal Cancer Screening in Brazil: The First Two Years of the Implementation Program in Barretos Cancer Hospital.

Cancer Prev Res (Phila) 2021 02 30;14(2):241-252. Epub 2020 Sep 30.

Department of Prevention, Barretos Cancer Hospital, Barretos, Brazil.

Colorectal cancer is the second most common cancer in Brazil. Yet, a nationally organized colorectal screening program is not implemented. Barretos Cancer Hospital (BCH) is one of the largest Brazilian institution that cares for underserved patients. BCH developed a fecal immunochemical test (FIT)-based organized colorectal cancer screening program to improve colorectal cancer outcomes.This study aims to present the quality/performance measures of the first 2 years of the FIT-based colorectal cancer screening program and its impact on the colorectal cancer disease stage. Between 2015 and 2017, a total of 6,737 individuals attending the Outpatient Department of Prevention or the Mobile Unit of BCH, which visits 18 cities of Barretos county, ages 50 to 65 years, were personally invited by a health agent/nurse practitioner. Exclusion criteria were personal history of colorectal cancer, adenomatous polyps, inflammatory bowel disease, and colonoscopy, or flexible sigmoidoscopy performed in the past 5 years. European Union (EU) guidelines for colorectal cancer screening programs were evaluated. Overall, 92.8% returned the FIT, with an inadequate examination rate of 1.5%. Among the 6,253 adequately tested, 12.5% had a positive result. The colonoscopy compliance and completion rates were 84.6 and 98.2%, respectively. The PPVs were 60.0%, 16.5%, and 5.6% for adenoma, advanced adenoma, and cancer, respectively. Stage distribution of screen-detected cancers shows earlier stages than clinically diagnosed colorectal cancer cancers reported at BCH and Brazilian cancer registries. Our colorectal cancer screening program achieved desirable quality metrics, aligned with the EU guidelines. The observed shift toward earlier colorectal cancer stages suggests an exciting opportunity to improve colorectal cancer-related cancers in Brazil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-20-0179DOI Listing
February 2021

Cap-assisted endoscopy increases ampulla of Vater visualization in high-risk patients.

BMC Gastroenterol 2020 Jul 9;20(1):214. Epub 2020 Jul 9.

Department of Endoscopy, Barretos Cancer Hospital, Antenor Duarte Villela, 1331, Zip Code: 14784 400, Barretos, São Paulo, Brazil.

Background: Periampullary adenocarcinoma is a major clinical problem in high-risk patients including FAP population. A recent modification for visualizing the ampulla of Vater (AV) involves attaching a cap to the tip of the forward-viewing endoscope. Our aim was to compare the rates of complete visualization of AV using this cap-assisted endoscopy (CAE) approach to standard forward-viewing endoscopy (FVE). We also determined: (i) the rates of complications and additional sedation; (ii) the mean time required for duodenal examination; and (iii) the reproducibility among endoscopists performing this procedure.

Methods: We performed esophagogastroduodenoscopy for AV visualization in 102 > 18 years old using FVE followed by CAE. Video recordings were blinded and randomly selected for independent expert endoscopic evaluation.

Results: The complete visualization rate for AV was higher in CAE (97.0%) compared to FVE (51.0%) (p <  0.001). The additional doses of fentanyl, midazolam, and propofol required for CAE were 0.05, 1.9 and 36.3 mg. in 0.9, 24.5, and 77.5% patients, respectively. The mean time of duodenal examination for AV visualization was lower on CAE compared to FVE (1.41 vs. 1.95 min, p <  0.001). Scopolamine was used in 34 FVE and 24 CAE, with no association to AV complete visualization rates (p = 0.30 and p = 0.14). Three more ampullary adenomas were detected using CAE compared to FVE. Cap displacement occurred in one patient, and there was no observed adverse effect of the additional sedatives used. Kappa values for agreement between endoscopists ranged from 0.60 to 0.85.

Conclusions: CAE is feasible, reproducible and safe, with a higher success rate for complete visualization compared to FVE.

Trial Registration: ClinicalTrials.gov , NCT02867826 , 16 August 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-020-01361-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346639PMC
July 2020

Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Barretos Cancer Hospital.

Front Oncol 2020 4;10:145. Epub 2020 Mar 4.

Molecular Oncology Research Centre, Barretos Cancer Hospital, Barretos, Brazil.

Colorectal cancer (CRC) is the third most frequent and the second deadliest cancer worldwide. The ethnic structure of the population has been gaining prominence as a cancer player. The purpose of this study was to determine the genetic ancestry of Brazilian CRC patients. Moreover, we intended to interrogate its impact on patients' clinicopathological features. Retrospective observational cohort study with 1,002 patients with CRC admitted from 2000 to 2014 at Barretos Cancer Hospital. Following tumor DNA isolation, genetic ancestry was assessed using a specific panel of 46 ancestry informative markers. Survival rates were obtained by the Kaplan-Meier method, and the log-rank test was used to compare the survival curves. Multivariable Cox proportional regression models were used to estimate hazard ratios (HRs). We observed considerable admixture in the genetic composition, with the following average proportions: European 74.2%, African 12.7%, Asian 6.5%, and Amerindian 6.6%. The multivariate analysis for cancer-specific survival showed that clinical stage, lymphovascular invasion, and the presence of recurrence were associated with an increased relative risk of death from cancer ( < 0.05). High African proportion was associated with younger age at diagnosis, while high Amerindian proportion was associated with the mucinous histological subtype. This represents the larger assessment of genetic ancestry in a population of Brazilian patients with CRC. Brazilian CRC patients exhibited similar clinicopathological features as described in Western countries. Genetic ancestry components corroborated the significant admixture, and importantly, patients with high African proportion develop cancer at a younger age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065467PMC
March 2020

Microbiota Profile and Impact of in Colorectal Cancer Patients of Barretos Cancer Hospital.

Front Oncol 2019 29;9:813. Epub 2019 Aug 29.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of () DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with being the most abundant genus in the tumor tissue. In the validation dataset, was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor ( = 0.0033). DNA in the tumor tissue was significantly associated with proximal tumors ( = 0.001), higher depth of invasion ( = 0.014), higher clinical stages ( = 0.033), poor differentiation ( = 0.011), MSI-positive status ( < 0.0001), BRAF mutated tumors ( < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 ( < 0.0001), MSH2 ( = 0.003), and PMS2 ( < 0.0001). Moreover, the presence of DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; = 0.028) and overall survival (63.5 vs. 76.5%; = 0.037). Here we report, for the first time, the association of presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727361PMC
August 2019

Mutation profiling of cancer drivers in Brazilian colorectal cancer.

Sci Rep 2019 09 23;9(1):13687. Epub 2019 Sep 23.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-49611-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757044PMC
September 2019

mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome.

Infect Agent Cancer 2018 29;13:43. Epub 2018 Dec 29.

1Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, SP CEP 14784 400 Brazil.

Background: Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.

Objective: We analyzed hotspot gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of mutations with patients' clinical and pathological features.

Methods: The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.

Results: mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between mutations and patients' clinical features or mutation profile.

Conclusion: This is the first report on the presence of mutations in esophageal cancer associated with chagasic megaesophagus. The detection of mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13027-018-0216-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311070PMC
December 2018

Comparison of a New-generation Fecal Immunochemical Test (FIT) With Guaiac Fecal Occult Blood Test (gFOBT) in Detecting Colorectal Neoplasia Among Colonoscopy-referral Patients.

Anticancer Res 2019 Jan;39(1):261-269

Molecular Oncology Research Center, School of Health Sciences, University of Minho, Braga, Portugal

Background/aim: The aim of the present study was to compare fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening with the traditional guaiac-based FOB tests (gFOBT).

Materials And Methods: A cohort of 368 colonoscopy-referral patients were evaluated by i) the new-generation FIT: ColonView quick test (CV; Biohit Oyj, Finland) and ii) a conventional gFOBT HemoccultSENSA (HS; Beckman Coulter, USA). Three fecal samples were requested for both assays, and all subjects underwent diagnostic colonoscopy with biopsy confirmation. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and area under curve (AUC) were calculated for both tests using three endpoints: adenoma (A), advanced adenoma (AA) and adenocarcinoma (AC).

Results: Colonoscopy and biopsies disclosed normal mucosa in 90/378 (24.5%) subjects, early A in 108/368 (29.3%) cases, AA in 48/368 (13.0%) and AC in 37/368 (10.1%), and non-neoplastic conditions in the remaining 85 (30.3%). For the AC endpoint, the CV (Hb/Hp) test had 94.6% SE and 65.1% SP (AUC=0.799), while the HS test had SE of 75.7% and SP of 84.3% (AUC=0.800). For the A endpoint, the difference between CV and HS was even more pronounced; SE of 44.2% and 19.2%, respectively (p<0.0001). Hb and Hb/Hp complex of the CV test showed equal performance for all endpoints.

Conclusion: Sensitivity (94.6%) of the ColonView quick test for the most reproducible endpoint (invasive CRC) far exceeded the pooled sensitivity (79%) estimated in a recent meta-analysis for 8 common FIT brands. As shown in a previous study, ColonView quick test is superior in SE to HemoccultSENSA test, making CV a perfect FIT for organized CRC screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13106DOI Listing
January 2019

Presence of microsatellite instability in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

Biomark Med 2018 06 6;12(6):573-582. Epub 2018 Jun 6.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.

Aim: The molecular pathogenesis of esophageal squamous cell carcinoma (ESCC) has been increasingly studied, but there is no report on the role of MSI in ESCC development associated with chagasic megaesophagus (CM).Results/methodology: In four ESCC/CM (4/19) we found microsatellite instability (MSI) alterations (21.1%), being three MSI-L (15.8%) and one MSI-H (5.3%). Four out of 35 ESCC cases showed MSI-L (11.4%) and only one out of 26 CM cases presented MSI-L (3.9%). The MSI-H was observed in an ESCC/CM patient that presents lack of MSH6 immunostaining corroborating deficiency in MMR pathway. Interestingly, the MSI-H ESCC/CM case also presented a deletion the HSP110 poly(T)17 gene.

Discussion/conclusion: Taking together, we concluded that MSI is a rare event in esophageal squamous cell carcinoma, but can be associated with CM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2017-0329DOI Listing
June 2018

Lack of microsatellite instability in gastrointestinal stromal tumors.

Oncol Lett 2017 Nov 4;14(5):5221-5228. Epub 2017 Sep 4.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784-400, Brazil.

The microsatellite instability (MSI) phenotype may constitute an important biomarker for patient response to immunotherapy, particularly to anti-programmed death-1 inhibitors. MSI is a type of genomic instability caused by a defect in DNA mismatch repair (MMR) proteins, which is present mainly in colorectal cancer and its hereditary form, hereditary nonpolyposis colorectal cancer. Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase () or platelet-derived growth factor receptor α (), which are oncogenes that predict the response to imatinib mesylate. In addition to mutations, other molecular alterations are important in GIST development. In GISTs, the characterization of the MSI phenotype is scarce and the results are not consensual. The present study aimed to assess MSI in a series of 79 GISTs. The evaluation of MSI was performed by pentaplex polymerase chain reaction comprising five markers, followed by capillary electrophoresis. The expression of MMR proteins was evaluated by immunohistochemistry. Regarding the /B-Raf proto-oncogene, serine/threonine kinase molecular profile of the 79 GISTs, 83.6% of the tumors possessed mutations, 10.1% had mutations and 6.3% were triple wild-type. The mutated- cases were associated with gastric location and a lower mitotic index compared with -mutated and wild-types, and these patients were more likely to be alive and without cancer. MSI analysis identified 4 cases with instability in one marker, however, additional evaluation of normal tissue and immunohistochemical staining of MMR proteins confirmed their microsatellite-stable nature. The results of the present study indicated that MSI is not involved in GIST tumorigenesis and, therefore, cannot serve as a biomarker to immunotherapy response in GIST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.6884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662911PMC
November 2017

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

Infect Agent Cancer 2017 13;12:54. Epub 2017 Oct 13.

Teaching and Research Institute, Barretos Cancer Hospital - Pius XII Foundation, Rua Antenor Duarte Vilela, 1331, Dr. Paulo Prata, Barretos, São Paulo 14784-400 Brazil.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC.

Methods: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression.

Results: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men ( = 0.025) had poor specific-cancer survival and a shorter progression-free survival ( = 0.050) as compared to women; III or IV clinical stage ( < 0.019) had poor specific-cancer survival and a shorter progression-free survival ( < 0.001) compared to I and II clinical stage; not submitted to surgery (<0.001) and not submitted to chemoradiotherapy ( = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival.

Conclusion: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13027-017-0163-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640908PMC
October 2017

Prevalence of high risk HPV DNA in esophagus is high in Brazil but not related to esophageal squamous cell carcinoma.

Histol Histopathol 2018 Apr 6;33(4):357-363. Epub 2017 Sep 6.

Teaching and Research Institute, Barretos Cancer Hospital - Pius XII Foundation, Brazil.

Backgrounds: The first publication that associated Human Papillomavirus (HPV) infection and esophageal cancer was published in 1982. However, data are still contradictory and require further investigation. The aim of this study was to identify high risk HPV DNA in esophageal tissue of patients with and without esophageal squamous cell carcinoma (ESCC) and correlate HPV presence with classical risk factors.

Methods: Invited patients signed the informed consent form, and interviews were conducted in order to obtain information about sociodemographic and lifestyle behavior. During endoscopy, esophageal biopsies were collected from case and controls. Multiplex polymerase chain reaction genotyping was conducted on endoscopic biopsies to identify HPV types and HPV-16 was further evaluated by specific PCR real time.

Results: Among 87 cases, 12 (13.8%) had tumors harboring high risk HPV DNA and among 87 controls, 12 (13.8%) had high risk HPV DNA (OR:1.025 [CI:0.405:2.592]). Variables regarding consumption of alcohol and use of tobacco continued to characterize risk factors even after adjustments by presence or absence of high risk HPV.

Conclusion: HPV was demonstrated to be frequently and similarly associated to normal and malignant esophageal tissues, but not as an independent risk factor to esophageal cancer.

Impact: To contribute to the Brazilian population data on this subject, which is still contradictory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14670/HH-11-929DOI Listing
April 2018

The Relation of HPV Infection and Expression of p53 and p16 Proteins in Esophageal Squamous Cells Carcinoma.

J Cancer 2017 9;8(6):1062-1070. Epub 2017 Apr 9.

Teaching and Research Institute, Molecular Oncology Research Center, Barretos Cancer Hospital - Pio XII Foundation, Brazil.

To investigate the HPV prevalence and characterize the expression of potential molecular surrogate markers of HPV infection in esophageal squamous cell carcinoma. The prevalence of HPV in individuals with and without esophageal cancer (EC) was determined by using multiplex PCR; p16 and p53 protein levels were assessed by immunohistochemistry (IHC). High-risk HPV (hr-HPV) was found in the same frequency (13.8%) in esophageal squamous cell carcinoma (ESCC) and in healthy individuals. The p53 expression was positive in 67.5% of tumor tissue, 20.0% of adjacent non-tumoral tissue and 1.8% of normal esophageal tissue. p16 was positive in 11.6% of esophageal cancer cases and 4.7% of adjacent non-tumoral tissue. p16 was undetectable among control group samples. p53 and p16 levels were not significantly associated with the HPV status. These results suggest that hr-HPV types are not associated with the development of ESCC and that p53 and p16 protein expression have no relationship with HPV infection in normal or cancerous esophagus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.17080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436260PMC
April 2017

Comparison between two different parameters of argon plasma coagulation in the treatment of chronic radiation proctopathy.

Int J Colorectal Dis 2016 Sep 26;31(9):1657-8. Epub 2016 Apr 26.

Department of Endoscopy, Barretos Cancer Hospital, Rua Antenor Duarte Vilella, 1331, Barretos, SP, Brazil, CEP 14784-400.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00384-016-2594-6DOI Listing
September 2016

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Eur J Hum Genet 2015 Jun 24;23(6):877-9. Epub 2014 Sep 24.

1] Molecular Oncology Research Center, Barretos Cancer Hospital, Sao Paulo, Brazil [2] Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal [3] ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2014.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795049PMC
June 2015

Serrated pathway in colorectal carcinogenesis.

World J Gastroenterol 2014 Mar;20(10):2634-40

Letícia Yamane, Rui Manuel Reis, Denise Peixoto Guimarães, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, 14780-000 São Paulo, Brazil.

Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v20.i10.2634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949272PMC
March 2014

Involvement of signaling molecules in the prediction of response to imatinib treatment in metastatic GIST patients.

J Surg Res 2012 Nov 5;178(1):288-93. Epub 2012 Apr 5.

Coordination of Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.

Imatinib therapy has undoubtedly contributed to the treatment of metastatic gastrointestinal stromal (GIST) tumors that were previously untreatable. However, disease progression during treatment with tyrosine kinase inhibitors remains an issue in clinical practice not fully explained by KIT and PDGFRA mutation status. We investigated the role of three important signaling molecules (insulin-like growth factor 1 receptor [IGF1R], protein kinase C-θ [PKCθ], and Raf kinase inhibitor protein [RKIP]) that have been implicated in GIST pathogenesis as potential biomarkers for prediction of response to imatinib treatment. We retrospectively reviewed 76 patients with metastatic GIST submitted to imatinib treatment between 2002 and 2007, and analyzed 63 of them. Insulin-like growth factor 1, total PKCθ, phosphorylated PKCθ, and RKIP immunohistochemical expression were correlated with objective response to imatinib treatment and progression-free and overall survival. Median follow-up was 31.2 mo (95% confidence interval, 26.3-36.1 mo). There was a statistically significant association between IGF1R expression and type of response to imatinib treatment (P = 0.05)-that is, higher IGF1R expression was related to lower objective response. However, IGF1R higher expression did not affect progression-free and overall survival. Insulin-like growth factor 1, but not PKCθ and RKIP, emerges as a potential biomarker for prediction of response to imatinib treatment in metastatic GISTs. Validation studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2012.03.031DOI Listing
November 2012

Prognostic relevance of KIT and PDGFRA mutations in gastrointestinal stromal tumors.

Anticancer Res 2010 Jun;30(6):2407-14

Center of Bone Marrow Transplantation (CEMO), Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.

Background: Prediction of biological behavior is crucial for selection of new therapeutic modalities in GIST. Here, we aimed to assess whether KIT and PDGFRA mutations have survival impact in gastrointestinal stromal tumors (GIST).

Patients And Methods: Fifty-five Brazilian patients with completely resected GIST were examined for KIT and PDGFRA mutations. The 5-year disease-free survival (DFS) was analyzed.

Results: KIT and PDGFRA mutations were identified in 74.5% and 7.3% of patients, respectively. The 5-year DFS rate for all patients was 52.8%. The 5-year DFS rate was lower in patients with tumors having in-frame deletions or concomitant in-frame deletions and insertions affecting codons 557-558 than in patients with tumors having other exon 11 KIT mutations (p=0.023). Conversely, when the patients with concomitant deletion-insertion mutations affecting codons 557-558 were excluded from the analysis, deletions involving codons 557-558 had no influence on 5-year DFS rates.

Conclusion: Our findings indicate that a specific KIT mutation may be associated with unfavorable behavior in GIST. This finding may have implications on selecting patients for adjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2010

Outpatient percutaneous endoscopic gastrostomy in selected head and neck cancer patients.

Surg Endosc 2009 Jul 5;23(7):1487-93. Epub 2009 Mar 5.

Department of Digestive Endoscopy, Cancer Hospital I, National Cancer Institute, Rio de Janeiro, RJ, Brazil.

Background: Percutaneous endoscopic gastrostomy (PEG) is a relatively simple and safe method of providing access for enteral feeding. The procedure is usually performed in hospitalized patients. The feasibility of PEG as an outpatient procedure has not been well estabilished in the medical literature. The main objective of this study was to investigate the feasibility and safety of PEG as an outpatient procedure in a selected group of head and neck cancer patients.

Patients And Methods: In this prospective cohort study, head and neck cancer subjects in good clinical condition were selected and enrolled in a close follow-up protocol of outpatient PEG. The clinical and demographic variables evaluated were age, gender, early complications, and timing of PEG.

Results: Of a total of 136 PEG patients, 129 (94.8%) were discharged 3 h after the procedure. Three were excluded from the study and four were hospitalized because of moderate abdominal pain. The rate of minor complications was 17.6% (local pain, 7.4%; wound infection, 6.6%; abdominal pain, 2.9%; hematoma, 0.7%). Major complications occurred in 2.2% of the procedures (buried bumper syndrome, 1.5%; early tube displacement, 0.7%). There was no mortality.

Conclusion: Ambulatory placement of gastrostomy tubes is viable and safe in head and neck cancer patients in good clinical condition. The early complication rates are similar to those described for hospitalized patients. Unnecessary admissions are avoided and costs of hospitalization are reduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-009-0381-yDOI Listing
July 2009
-->