High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas

Contains fulltext : 80487.pdf (publisher's version ) (Open Access)BACKGROUND: The diagnosis of benign renal oncocytomas (RO) and chromophobe renal cell carcinomas (RCC) based on their morphology remains uncertain in several cases. METHODS: We have applied Affymetrix GeneChip Mapping 250 K NspI high-density oligoarrays to identify small genomic alterations, which may occur beyond the specific losses of entire chromosomes, and also Affymetrix GeneChip HG-U133 Plus2.0 oligoarrays for gene expression profiling. RESULTS: By analysing of DNA extracted from 30 chRCCs and 42 ROs, we have confirmed the high specificity of monosomies of chromosomes 1, 2, 6, 10, 13, 17 and 21 in 70-93% of the chRCCs, while ROs displayed loss of chromosome 1 and 14 in 24% and 5% of the cases, respectively. We demonstrated that chromosomal gene expression biases might correlate with chromosomal abnormalities found in chromophobe RCCs and ROs. The vast majority genes downregulated in chromophobe RCC were mapped to chromosomes 2, 6, 10, 13 and 17. However, most of the genes overexpressed in chromophobe RCCs were located to chromosomes without any copy number changes indicating a transcriptional regulation as a main event. CONCLUSION: The SNP-array analysis failed to detect recurrent small deletions, which may mark loci of genes involved in the tumor development. However, we have identified loss of chromosome 2, 10, 13, 17 and 21 as discriminating alteration between chromophobe RCCs and ROs. Therefore, detection of these chromosomal changes can be used for the accurate diagnosis in routine histology

Antioxidants and breast cancer risk- a population-based case-control study in Canada

<p>Abstract</p> <p>Background</p> <p>The effect of antioxidants on breast cancer is still controversial. Our objective was to assess the association between antioxidants and breast cancer risk in a large population-based case-control study.</p> <p>Methods</p> <p>The study population included 2,362 cases with pathologically confirmed incident breast cancer (866 premenopausal and 1,496 postmenopausal) and 2,462 controls in Canada. Intakes of antioxidants from diet and from supplementation as well as other potential risk factors for breast cancer were collected by a self-reported questionnaire.</p> <p>Results</p> <p>Compared with subjects with no supplementation, 10 years or longer supplementation of zinc had multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of 0.46 (0.25-0.85) for premenopausal women, while supplementation of 10 years or longer of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc had multivariable-adjusted ORs (95% CIs) of 0.74 (0.59, 0.92), 0.58 (0.36, 0.95), 0.79 (0.63-0.99), 0.75 (0.58, 0.97), and 0.47 (0.28-0.78), respectively, for postmenopausal women. No significant effect of antioxidants from dietary sources (including beta-carotene, alpha-carotene, lycopene, lutein and zeaxanthin, vitamin C, vitamin E, selenium and zinc) or from supplementation less than 10 years was observed.</p> <p>Conclusions</p> <p>This study suggests that supplementation of zinc in premenopausal women, and supplementation of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc in postmenopausal women for 10 or more years may protect women from developing breast cancer. However, we were unable to determine the overall effect of total dose or intake from both diet and supplement.</p

Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome

Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. The NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. In a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype–phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment