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Cancers Aug 2023The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can... (Review)
Review
The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can be upregulated or decreased in different tumors. The literature research was conducted manually by the authors using the PubMed database by searching articles published before 2023 with the combination of several nectin-related keywords. A total of 43 studies were included in the main section of the review. Nectins-1-3 have different expressions in tumors. Both the loss of expression and overexpression could be negative prognostic factors. Nectin-4 is the best characterized and the most consistently overexpressed in various tumors, which generally correlates with a worse prognosis. New treatments based on targeting nectin-4 are currently being developed. Enfortumab vedotin is a potent antibody-drug conjugate approved for use in therapy against urothelial carcinoma. Few reports focus on hepatocellular carcinoma, which leaves room for further studies comparing the utility of nectins with commonly used markers.
PubMed: 37568798
DOI: 10.3390/cancers15153983 -
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 -
Pathology, Research and Practice Aug 2023Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16 has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16 immunohistochemical expression and the risk of malignization of OPMDs.
MATERIAL AND METHODS
After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16 expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests.
RESULTS
Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier.
CONCLUSION
Pooled analysis showed that p16 assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16 overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.
Topics: Humans; Cyclin-Dependent Kinase Inhibitor p16; Biomarkers, Tumor; Prognosis; Precancerous Conditions; Mouth Neoplasms
PubMed: 37406376
DOI: 10.1016/j.prp.2023.154656 -
Archives of Pathology & Laboratory... Sep 2023To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2)...
PURPOSE.—
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.
METHODS.—
The Update Panel conducted a systematic literature review to identify signals for updating recommendations.
RESULTS.—
The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations.
RECOMMENDATIONS.—
The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.
DISCUSSION.—
HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.
Topics: Humans; Female; Breast Neoplasms; In Situ Hybridization, Fluorescence; Receptor, ErbB-2; In Situ Hybridization; Biomarkers, Tumor
PubMed: 37303228
DOI: 10.5858/arpa.2023-0950-SA -
Cureus May 2023Heat shock proteins (HSPs) are expressed in a variety of cancers in human beings and are correlated with differentiation, proliferation, and metastasis. Head and neck... (Review)
Review
Heat shock proteins (HSPs) are expressed in a variety of cancers in human beings and are correlated with differentiation, proliferation, and metastasis. Head and neck squamous cell carcinomas, like other tumors, are exposed to environmental stress, and lack of oxygen and nutrients, and in such situations, hypoxic inducible factor (HIF) initiates the expression of genes causing angiogenesis, invasion, and metastasis. Extracellular heat shock proteins 90 alpha (eHSP90α) are overexpressed in cancers leading to tumor progression and metastasis. Hence, this review will focus on the role of eHSP90α in the metastasis of oral squamous cell carcinomas (OSCC). Different online databases were scoured for relevant articles from October 2000 to October 2022. A total of 342 articles along with duplicates were excluded. The retrieved 45 articles were studied and 39 of them were found to be not eligible as they lacked intervention and their outcome measures did not match with the present review. The final qualitative evaluation included four articles that fulfilled the eligibility criterion. A definitive expression of HSP90 was implicated, as seen in three studies, suggesting its probable role as a prognostic marker for OSCC, but no conclusive evidence was found. The present review suggests that eHSP90α plays a significant role in OSCC. Though a positive association was found between HSP90 expression and its possible correlation with metastasis, affirmative evidence can only be derived with the conduction of many more research studies and their subsequent synthesis of results.
PubMed: 37273315
DOI: 10.7759/cureus.38514 -
Asian Pacific Journal of Cancer... May 2023This study aimed to investigate the level of PD-L1 protein expression in patients with BCs who were of Asian descent. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to investigate the level of PD-L1 protein expression in patients with BCs who were of Asian descent.
METHODS
Three databases were conducted on this article up to August 10th, 2022. The reference lists of the publications were examined for further studies, and in cases of duplicates, a study with a larger sample size was added. In survival analysis, the hazard ratio (HR) was applied to the circumstances characterized by the frequency of occurrences, and for the clinicopathological characteristic, the best-adjusted odds ratio (OR) with a 95% confidence interval (CI) was employed. The Newcastle-Ottawa Scale (NOS) was utilized to evaluate selection criteria, comparison, and exposure to establish the quality of the technique in the under-consideration studies. The Z test determined the association analysis of OS, DFS, and clinicopathological characteristics with PD-L1 expression.
RESULT
All eight trials for OS and six for DFS were considered, with 4.111 and 3.071 participants, respectively. Overexpression of PD-L1 was linked to a reduced OS compared to individuals with undetectable expression (HR= 1.58, 95% CI 1.04-2.40; P=0.03). We analyzed clinicopathological features, and it elevated in individuals with histological grade III (OR=2.39, 95% CI 1.26-4.54; P=0.008) and positive node (OR=0.68, 95% CI 0.48-0.97; P<0.05).
CONCLUSION
Overexpression of PD-L1 was associated with a shorter OS in BCs patients. High PDL1 was higher in persons with nodal positivity and histological grade III.
Topics: Female; Humans; B7-H1 Antigen; Breast Neoplasms; Prognosis; Proportional Hazards Models; Survival Analysis
PubMed: 37247264
DOI: 10.31557/APJCP.2023.24.5.1453 -
Journal of Oral and Maxillofacial... 2023Odontogenic keratocyst (OKC) is an aggressive odontogenic lesion that has been the subject of continuous dispute about its biological activity and classification.... (Review)
Review
Odontogenic keratocyst (OKC) is an aggressive odontogenic lesion that has been the subject of continuous dispute about its biological activity and classification. 'Numerous studies are being conducted to see how much more or lower expression of the tumour-suppressing p53 protein is in the odontogenic cyst than in the dentigerous cyst (DC) or ameloblastic tumours. The aim was to find immunohistochemistry studies reporting on OKCs, DCs and ameloblastomas (AMBs); we searched MEDLINE, WEB of Science and SCOPUS. Effects may be shown to exist when the risk difference (RD) between lesions overexpressing and those without the p53 protein was a value of less than 0.05. A total of 129 records were returned in the first hit. After the elimination of duplicates, there were 89 items, of which 18 were deemed eligible for inclusion. According to a meta-analysis of 13 studies including OKCs, DCs and AMB, the chance of p53 expression in OKCs is assessed to be 23 per cent higher ( = 0.003) than in DCs, whereas the probability is predicted to be 4 per cent lower ( = 0.028) than in AMBs. OKCs appear to act more like cancers than odontogenic sores as far as p53 articulation, and the order of this illness into the keratocystic odontogenic tumour (KCOT) ought to be rethought.
PubMed: 37234299
DOI: 10.4103/jomfp.jomfp_58_22 -
Annals of Medicine Dec 2023We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.
MATERIALS AND METHODS
We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR).
RESULTS
A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], < .001; ≥5%: 0.62 [0.52, 0.74], < .001; ≥10%: 0.42 [0.30, 0.59], < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], = .02), with liver metastases (OS: 1.16 [1.02,1.32], = .02) and antibiotics (OS: 3.13 [1.25,7.84], < .001; PFS: 2.54 [1.38, 4.68], = .003).
CONCLUSION
The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Randomized Controlled Trials as Topic
PubMed: 37212453
DOI: 10.1080/07853890.2023.2215543 -
Critical Reviews in Oncology/hematology Jul 2023Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The... (Meta-Analysis)
Meta-Analysis Review
Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms
PubMed: 37210016
DOI: 10.1016/j.critrevonc.2023.104021 -
Diagnostic Pathology Apr 2023Hypoxia is a characteristic of many solid tumours and an adverse prognostic factor for cancer therapy. Hypoxia results in upregulation of carbonic anhydrase IX (CAIX)... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Hypoxia is a characteristic of many solid tumours and an adverse prognostic factor for cancer therapy. Hypoxia results in upregulation of carbonic anhydrase IX (CAIX) expression, a pH-regulating enzyme. Many human tissue studies have examined the prognostic value of CAIX expression in breast cancer but have yielded inconsistent results. Therefore, a systematic review and meta-analysis was undertaken to assess the prognostic value of CAIX expression for breast cancer patients.
METHODS
The electronic databases were systematically searched to identify relevant papers. The clinical outcomes included disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) in breast cancer patients. Review Manager version 5.4 was employed to analysis data from 23 eligible studies (containing 8390 patients).
RESULTS
High CAIX expression was associated with poorer RFS [HR = 1.42, 95% CI (1.32-1.51), p < 0.00001], DFS [HR = 1.64, 95% CI (1.34-2.00), p < 0.00001], and OS [HR = 1.48, 95% CI (1.22-1.80), p < 0.0001]. Heterogeneity was observed across the studies. There was an effect of the CAIX antibody employed, scoring methods, and tumour localisation on CAIX expression.
CONCLUSION
CAIX overexpression was significantly associated with poorer RFS, DFS, and OS in breast cancer patients. However, further work in high quantity tissue cohorts is required to define the optimal methodological approach.
Topics: Humans; Female; Carbonic Anhydrase IX; Breast Neoplasms; Carbonic Anhydrases; Biomarkers, Tumor; Antigens, Neoplasm; Prognosis; Hypoxia
PubMed: 37061698
DOI: 10.1186/s13000-023-01325-9