Soluble levels of 4-1BB (CD137) and OX40 (CD134) are associated with cancer progression in gastric adenocarcinoma.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that soluble forms of T-cell costimulatory molecules 4-1BB (s4-1BB) and OX40 (sOX40) interact with immune cells and may constitute a mechanism of immune evasion by tumors in various cancers. The role of the soluble forms of 4-1BB and OX40 in GC remains unclear. We aimed to examine the association between serum levels of s4-1BB and sOX40 and tumor progression in patients with GC. METHODS: Between 2017 and 2018, a cross-sectional study was performed with serum samples of 83 GC patients and 20 healthy controls. RESULTS: Patients with stage IV metastatic gastric cancer had significantly higher levels of soluble OX40 in comparison with stage III patients with lymph nodes metastasis (p = 0.0003) and stages I and II patients (p = 0.005), whereas the opposite was found for soluble 4-1BB levels, with lower levels being found in advanced stage III (p = 0.003) compared with initial stages I/II. CONCLUSIONS: The sOX40 and s4-1BB-mediated T cell interactions may be involved in antitumor immune responses in GC, possibly favoring tumor escape and progression. Serum levels of sOX40 and s4-1BB are associated with staging in GC and may constitute biomarkers for prognosis, as well as potential targets for immunotherapy.

Evaluation of soluble co-inhibitors and co-stimulators levels of the immune response in gastric cancer.

BACKGROUND: Co-inhibitor and co-stimulator mediators trigger actions that result in immunological homeostasis and are being evaluated as potential therapeutic targets in gastric cancer (GC). OBJECTIVE: To evaluate the soluble levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL in GC patients. METHODS: The cross-sectional study was carried out at the Hospital de Cancer de Pernambuco, Brazil between 2017 and 2018. A total of 74 GC patients and 30 healthy controls were included. RESULTS: Low levels of sPD1 (p = 0.0179), sPDL2 (p = 0.0003), and sGal9 (p < 0.0001), and higher levels of sPDL1 (p = 0.004), sTIM-3 (p = 0.0072), sGITR (p = 0.0179), and sGITRL (p = 0.0055) compared to the control group. High sPD-1, sTIM-3, and sGal9 levels in stage IV compared I/II and III (p < 0.05). High sPDL1, sGal9, and sGITRL levels in esophagogastric junction compared to body and Pylorus/Antrum groups (p < 0.05). No significant differences were observed in sPD1, sPDL1, sPDL2, sTIM3, sGal9, sGITR, and sGITRL levels between the intestinal, diffuse, and mixed GC groups. Low sGITR levels in GC patients who died within the first 24 months compared to the who survived (p = 0.0332). CONCLUSIONS: There is an association of sPD1, sTIM-3, and sGal9 with disease progression and sGITR with death, these mediators may be potential prognostic biomarkers in GC.

The effect of chemotherapy on dietary intake and nutritional status in patients with colorectal neoplasms and the importance of nutritional counseling.

PURPOSE: This study aimed at assessing the effect of chemotherapy on dietary intake and nutritional status of patients with colorectal cancer undergoing chemotherapy. METHODS: Observational, cross-sectional study conducted with 35 patients of both sexes, aged 50 years or older. Dietary intake was assessed four times: before (T0), twice during (T1 and T2), and after (TF) chemotherapy. Data on energy, macronutrients, and micronutrients were used for assessing dietary intake. Nutritional status was assessed on the first day and at the end of the chemotherapy cycle. The data were treated statistically using a 5% significance level. RESULTS: The intake of energy, carbohydrates, lipids, selenium, and iron was lower after chemotherapy infusion (p < 0.05). Energy consumption decreased when comparing T0 (1419.8 ± 527.1 kcal) with T1 (1181.9 ± 423.2 kcal). Regarding macronutrients, carbohydrates and lipids showed a drop (p < 0.05), but there were no differences in protein intake, and it was observed that the consumption of food sources such as dairy was prioritized. In the analysis of vitamins and minerals, vitamins dropped but without a significant difference. There were significant differences between T1 and TF for iron (9.7 mg ± 4.5 mg and 12.0 ± 4.0 mg) and selenium (77.4 ± 29.7 µg and 93.6 ± 37.8 µg). There was no change in body composition and nutritional status between chemotherapy cycles. CONCLUSION: The treatment reduced patients' food consumption after the chemotherapy session and impacted dietary intake, which demonstrates the importance of nutritional counseling and intervention, especially on energy consumption.

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.

BACKGROUND: The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. METHODS: Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. RESULTS: Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle < 5°, VAT < 163.8 cm2 in men and <  80.1 cm2 in women, and sarcopenia were associated with the relative risk of death, with respective hazard ratios/odds ratios and 95% confidence intervals of 8.77 (1.14-67.1), 3.95 (1.11-14.0), 3.79 (1.10-13.1), 3.43 (1.03-11.4), and 3.95 (1.06-14.6). Increased VAT was associated with a lower risk of death, even in patients older than 60 years or those harboring mutated KRAS. CONCLUSIONS: Patients with positive indicators for malnutrition or risk of malnutrition had an increased risk of death. No relationship was identified between the presence of mutations and survival.

Cachexia Stage, Patient-Generated Subjective Global Assessment, Phase Angle, and Handgrip Strength in Patients with Gastrointestinal Cancer.

The aim of this study was to correlate patients with gastrointestinal cancer, classified according to different stages of cancer cachexia (SCC) as proposed by Fearon, with nutritional assessment tools such as PG-SGA, phase angle (PA), and handgrip strength. One hundred one patients with a mean age of 61.8 ± 12.8 yr, with 58.4% being men were included. 32.6% were malnourished according to the body mass index (BMI). A severe or moderate malnutrition had been diagnosed in 63.3% when assessed using the PG-SGA, 60.4% had decreased handgrip strength, and 57.4% had lower grades of PA. Among the patients in the study, 26% did not have cachexia, 11% had precachexia, 56% cachexia, and 8% refractory cachexia. The PG-SGA, PA, and handgrip strength were associated with cachexia (P ≤ 0.001). An increased risk of death was found in patients with cachexia [RR: 9.1; confidence interval (CI) 95%: 0.1-90.2, P = 0.039], refractory cachexia (RR: 69.4, CI 95%: 4.5-1073.8, P = 0.002), and increased serum C-reactive protein (CRP) levels (P < 0.001). In conclusion, most of the patients with digestive system cancer had cachexia or refractory cachexia in the first nutritional assessment. Nutritional risk, as determined by PG-SGA, was correlated with PA and handgrip strength. High CRP levels, cachexia, and refractory cachexia were prognostic factors for cancer patients.

Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

Grape juice concentrate (G8000™) modulates apoptosis but not oxidative stress following rat colon carcinogenesis induced by azoxymethane.

OBJECTIVES: The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis. MATERIAL AND METHODS: For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate. RESULTS: The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p > 0.05) among groups. CONCLUSION: In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.

Expression of galectin-3 in gastric adenocarcinoma.

BACKGROUND & OBJECTIVES: Galectin-3 a member of the galectin family is an endogenous ß-galactoside binding lectin. It has been found to be associated with cell adhesion, recognition, proliferation, differentiation, immunomodulation, angiogenesis, apoptosis and can be a reliable marker for cancer aggressiveness. The aim of this study was to verify protein expression in gastric adenocarcinoma tissues and correlate the results with the clinical aspects in the study population. METHODS: Galectin-3 expression was examined by immunohistochemistry in 57 samples of gastric adenocarcinomas tissues. Galectin-3 protein expression was observed in the cytoplasm and the nucleus of examined tissues. RESULTS: Thirty one (54.4%) samples had strong or moderate staining and 26 (45.6%) tumours had negative or weak staining. The galectin-3 did not show association with the sex (p=0.347), age (p=0.999), Lauren's classification (p=0.731) and TNM stage (p=0.222). Regarding the TNM stage, 66.7 per cent of stage I tumours had strong or moderate staining; with tumours stage IV this percentage was 33.3 per cent. INTERPRETATION & CONCLUSION: Our results suggest that gal-3 is not a reliable biomarker for prognosis of the gastric adenocarcinoma by immunohistochemistry. Further studies need to be done on a large sample of tumour tissues in different clinical staging.

Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer.

Older individuals are more likely to develop solid cancers, but at the same time are more sensitive to the side effects of chemotherapy. In addition, older adults are more likely to present with chronic diseases (comorbidities) and immunosenescence that may decrease immunosurveillance against cancer. Clinical outcomes for the older patient with cancer are different from the younger patient and require different research and treatment approaches. Thus, alternative therapeutic approaches tailored specifically to the older patients are required. Colorectal cancer (CRC) has a high incidence in older individuals and is the third leading cause of cancer death globally. Anti-hypertensives are used by a large proportion of older patients and some studies have pointed to a positive impact of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on CRC outcomes. As we have previously shown in a mouse model, lung metastases express ACE and contain many infiltrating myeloid-derived suppressor cells (MDSC); particularly high levels of MDSC are also present in the blood of older patients with CRC and other cancers, and are associated with disease severity. In this Commentary, we hypothesize that one mechanism responsible for the positive impact of ACEi or ARB on the outcome of CRC is the modulation of myeloid cells contributing to their maturation to non-suppressive neutrophils/monocytes and diverting them away from retaining an immature MDSC phenotype.

IMMUNOEXPRESSION OF DEK AND PHOSPHO-P38 PROTEINS IN RECTAL CANCER BEFORE CHEMORADIATION THERAPY.

BACKGROUND: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. OBJECTIVE: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. METHODS: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. RESULTS: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). CONCLUSION: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.

NONINVASIVE BREATH TESTS FOR DIAGNOSIS OF SIBO AND LACTOSE INTOLERANCE IN PATIENTS ON CHEMOTHERAPY TREATMENT FOR COLORECTAL AND GASTRIC CÂNCER.

BACKGROUND: Worldwide, colorectal cancer (CRC) and gastric cancer (GC) are the third and the fifth most prevalent, respectively. Diarrhea is a common symptom in patients on chemotherapy or radiotherapy treatment and can reduce treatment tolerance. Surgical resections and chemotherapy change the intestinal microbiota that can lead to lactose intolerance, small intestinal bacterial overgrowth (SIBO). OBJECTIVE: The aim of the study was to evaluate the frequency of diarrhea in patients with CRC and GC on chemotherapy with SIBO or intolerance of lactose. METHODS: This is a descriptive and observational study with patients of both sexes, over 18 years old, in treatment in the Gastro-Oncology outpatient clinic of the Federal University of São Paulo. Patients with a confirmed diagnosis of CRC or GC during chemotherapy treatment were included. To detect bacterial overgrowth and lactose intolerance, breath hydrogen test with lactulose and lactose was done. Number and aspects of the evacuations and toxicity degree were collected. For the nutritional assessment, weight and height were performed to calculate the BMI. and the Patient Generated Subjective Global Assessment (PG-SGA). RESULTS: A total of 33 patients were included, 29 with CRC and 3 with GC. Most of them were male (57.57%), mean age of 60.03±10.01 years and in chemotherapy with fluoropyrimidine and oxaliplatin (54.5%). Diarrhea was present in 57.6% and 30.3% had toxicity grade 2. According to the BMI, 78.9% were eutrophics, obese or overweight, but according to PG-SGA, 84.9% had moderate or severe nutritional risk grade. Between patients, 45% had lactose intolerance and 9% SIBO. Diarrhea grade 2-3 was observed in 66.6% of patients with SIBO and 66.7% of that with lactose intolerance. No statistical difference was observed between patients with SIBO or lactose intolerance and grade of diarrhea. CONCLUSION: Diarrhea was a frequent symptom in chemotherapy patients with gastric or colorectal cancer independent of the presence of SIBO or lactose intolerance. Surgery and chemotherapy treatment impacted in the intestinal habit of patients. Diagnosis of other causes of diarrhea may contribute to a better tolerance to treatment and quality of life.

RNAM EXPRESSION AND DNA METHYLATION OF DKK2 GENE IN COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

BACKGROUND: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. AIM: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. METHODS: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. CONCLUSION: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.

p53, Cyclin-D1, ß-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria.

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, ß-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. OBJECTIVE: To study the expression of p53, Cyclin D1, ß-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. PATIENTS AND METHODS: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, ß-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. RESULTS: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. CONCLUSIONS: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.
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Label-free peptide quantification coupled with in silico mapping of proteases for identification of potential serum biomarkers in gastric adenocarcinoma patients.

OBJECTIVES: We aimed to identify serum level variations in protein-derived peptides between patients diagnosed with gastric adenocarcinoma (GAC) and non-cancer persons (control) to detect the activity changes of proteases and explore the auxiliary diagnostic value in the context of GAC physiopathology. METHODS: The label-free quantitative peptidome approach was applied to identify variants in serum levels of peptides that can differentiate GAC patients from the control group. Peptide sequences were submitted against Proteasix tool predicting proteases potentially involved in their generation. The activity change of proteases was subsequently estimated based on the peptides with significantly altered relative abundance. In turn, activity change prediction of proteases was correlated with relevant protease expression data from the literature. RESULTS: A total of 191 peptide sequences generated by the cleavage of 36 precursor proteins were identified. Using the label-free quantification approach, 33 peptides were differentially quantified (adjusted fold change ≥ 1.5 and p-value < 0.05) in which 19 were up-regulated and 14 were down-regulated in GAC samples. Of these peptides, fibrinopeptide A was significantly decreased and its phosphorylated form ADpSGEGDFLAEGGGVR was upregulated in GAC samples. Activity change prediction yielded 10 proteases including 6 Matrix Metalloproteinases (MMPs), Thrombin, Plasmin, and kallikreins 4 and 14. Among predicted proteases in our analysis, MMP-7 was presented as a more promising biomarker associated with useful assays of clinical practice for GAC diagnosis. CONCLUSION: Our experimental results demonstrate that the serum levels of peptides were significantly differentiated in GAC physiopathology. The hypotheses built on protease regulation could be used for further investigations to measure proteases and their activity levels that have been poorly studied for GAC diagnosis.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

BACKGROUND: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. AIM: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. METHODS: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. CONCLUSION: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.

E-cadherin and metalloproteinase-1 and -7 polymorphisms in colorectal cancer.

PURPOSE: E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). EXPERIMENTAL DESIGN: A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95% CI: 2.02-20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95% CI: 1.27-9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95% CI: 0.93-9.47, p=0.098). CONCLUSIONS: The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.

High-resolution melting for detecting KRAS mutations in colorectal cancer.

Colorectal cancer is a leading cause of cancer that may metastasize. KRAS gene sequence of exon 2 should be examined for identification of patients that can be treated with anti-EGFR. The aim of the present study was to evaluate the efficacy of high-resolution melting (HRM) to detect KRAS mutations in colorectal cancer (CRC) tumors. The exon 2 of KRAS was amplified from 47 adenocarcinoma CRC tissues. The tumors were subjected to high-resolution melt using quantitative PCR to identify wild-type and mutant subgroups. The results were compared to the mutations detected by next-generation sequences (NGS). The study included 47 patients, with a mean age of 62 years, of whom 24 patients were male. Most of the patients had stage II or stage III tumors. The mean melting temperatures for the wild-type and mutated group at exon 2 were 78.13˚C and 77.87˚C, respectively (P<0.001, 95% CI = 0.11-0.4). The sensitivity and specificity of high-resolution melting were 83.3 and 96.6%, respectively, with a high concordance between the NGS and HRM methods for detecting KRAS mutation in exon 2 (ĸ = 0.816; P=0.625). Thus, HRM could be used as an alternative method for detecting KRAS mutations in colorectal cancer tissue.