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Modern Pathology : An Official Journal... Oct 2022Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic...
Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.
Topics: Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; ErbB Receptors; Humans; In Situ Hybridization, Fluorescence; Nuclear Proteins; Proto-Oncogene Proteins p21(ras); Salivary Gland Neoplasms; Trans-Activators; Transcription Factors
PubMed: 35871081
DOI: 10.1038/s41379-022-01100-z -
The Oncologist Oct 2023HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes.
METHODS
A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses.
RESULTS
Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates.
CONCLUSIONS
While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.
Topics: Humans; Antibodies, Monoclonal; Colorectal Neoplasms; Retrospective Studies; ErbB Receptors; Panitumumab; Colonic Neoplasms; Rectal Neoplasms; Proto-Oncogene Proteins p21(ras); Antineoplastic Combined Chemotherapy Protocols
PubMed: 37463037
DOI: 10.1093/oncolo/oyad200 -
World Journal of Clinical Oncology Jan 2020Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different...
BACKGROUND
Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.
AIM
To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors.
METHODS
An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed.
RESULTS
Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E.
CONCLUSION
The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
PubMed: 31976308
DOI: 10.5306/wjco.v11.i1.31 -
Critical Reviews in Oncology/hematology Nov 2021Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common mutations with tumour budding.
METHODS
A systematic review of studies relating to tumour budding and genetic mutation in CRC was performed. The relationship between mutational status and tumour budding was evaluated using meta-analysis.
RESULTS
A total of 6153 patients from 17 articles were included. According to the meta-analysis, high-grade tumour budding was significantly associated with KRAS mutation (OR = 1.52, 95 %CI: 1.13-2.02, P = 0.005) and MSS/pMMR (OR = 2.06, 95 %CI: 1.42-2.97, P = 0.0001).
CONCLUSION
The significant association between high-grade tumour budding and mutated KRAS or MSS/pMMR may suggest a role of these mutations in the development of the tumour budding phenotype and be useful for stratifying patient outcome in CRC.
Topics: Colorectal Neoplasms; Humans; Mutation; Phenotype; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34619332
DOI: 10.1016/j.critrevonc.2021.103490 -
Diagnostics (Basel, Switzerland) Mar 2023Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type.... (Review)
Review
Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.
PubMed: 36980495
DOI: 10.3390/diagnostics13061187 -
Medicina (Kaunas, Lithuania) Mar 2023Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of... (Review)
Review
Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.
Topics: Humans; Becaplermin; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Intercellular Signaling Peptides and Proteins; Furcation Defects
PubMed: 37109634
DOI: 10.3390/medicina59040676 -
Arquivos Brasileiros de Cirurgia... 2019Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial.
AIM
To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk.
METHODS
The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR.
RESULTS
A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall.
CONCLUSIONS
The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.
Topics: Genetic Predisposition to Disease; Hirschsprung Disease; Humans; Polymorphism, Genetic; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Sensitivity and Specificity
PubMed: 31644668
DOI: 10.1590/0102-672020190001e1448 -
The Oncologist Nov 2023A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically...
PURPOSE
A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC).
DESIGN
Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC.
RESULTS
A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm.
CONCLUSION
Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Prevalence; Colorectal Neoplasms; Neoplasm Recurrence, Local; Mutation; Lung Neoplasms
PubMed: 37432264
DOI: 10.1093/oncolo/oyad138 -
Medicina (Kaunas, Lithuania) Jun 2022Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic... (Meta-Analysis)
Meta-Analysis Review
Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic invasion and distant metastases, resulting in poor prognosis. To date, there is still a lack of consensus on the genetic etiology underpinning this cancer subtype. This study aimed to clarify the molecular associations of SC by using meta-analysis and a systematic review. Methods: PubMed, Embase, and Cochrane Library were searched for studies evaluating the KRAS, BRAF, P53 statuses, and microsatellite instability (MSI) in CRC patients with different histological subtypes, including SC. The diagnosis of SC is defined as the signet ring cells comprising ≥50 percent of the tumor mass. By dividing the studies into subgroups based on the composition of control groups, such as classic adenocarcinoma (AC; no SC components) and non-SC (including those with SC components < 50%), the relative risk (RR) of molecular alterations for SC in each study were pooled using a random-effects model. Two reviewers identified trials for inclusion, assessed quality, and extracted data independently. Results: Data from 29 studies consisting of 9366 patients were included in this analysis. SC was associated positively with MSI (RR 1.78, 95% CI 1.34 to 2.37; 95% CI 0.77 to 4.15; p = 0.0005), BRAF mutation (RR 1.99, 95% CI 1.21 to 3.26; 95%CI 0.68 to 5.82; p = 0.0146), and negatively with KRAS mutation (RR 0.48, 95% CI 0.29 to 0.78; 95% CI 0.09 to 2.49; p = 0.0062). No association was found between SC and P53 expression (RR 0.92, 95% CI 0.76 to 1.13; 95%CI 0.61 to 1.39; p = 0.3790). Moreover, it was associated negatively with P53 gene mutations (RR 0.92, 95% CI 0.77 to 1.09; 95% CI 0.46 to 1.82; p = 0.1568), and P53 protein (RR 0.93, 95% CI 0.58 to 1.49; 95% CI 0.40 to 2.17; p = 0.6885). Conclusions: The molecular etiology of SC may be associated with the BRAF and MSI pathways. Its features, such as the high frequency of BRAF mutation, could partly explain its less favorable outcomes and limited effects of traditional chemotherapy.
Topics: Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Humans; Microsatellite Instability; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Tumor Suppressor Protein p53
PubMed: 35888555
DOI: 10.3390/medicina58070836 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0