•There is a probably underestimation of the malignant transformation potential of OLP.•Epithelial dysplasia should not be considered as an exclusion criterion for the diagnostic of OLP.•The most ...concerns aspects related with the risk of OSCC development in OLP patients are atrophic-erosive lesions in tongue.•Patients affected for OLP should be following for long periods, probably full life.•Tobacco, alcohol and HCV infection increase the risk of malignant transformation in OLP patients.
To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development.
We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses.
Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84–1.49), 1.88% for OLLs (95% CI = 0.15–4.95) and 1.71% for LRs (95% CI = 0.00–5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21–2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40–6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28–3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14–4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98–20.22, p = 0.053).
The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.
Programmed cell death‐ligand 1 (PD‐L1) is a transmembrane protein that acts as a co‐inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD‐1), is found on immune ...cells, where binding to PD‐L1 can reduce the proliferation of PD‐1‐positive cells, inhibit their cytokine secretion and induce apoptosis. PD‐L1 in immune‐privileged tissue plays a crucial role in peripheral tolerance. PD‐L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD‐1:PD‐L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD‐L1, including its structure, function and regulation. We also review studies on the overexpression of PD‐L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.
The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some ...candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin‐dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone‐dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.
Using a combination of genomic and metabolomic profiling strategies, the CAMKK2 kinase is identified as a critical downstream target of the androgen receptor. CAMKK2 regulates anabolic flux, and represents an attractive therapeutic target for prostate cancer treatments.
Background
To evaluate published evidence on the predictive value of CCND1 amplification/cyclin D1 overexpression as malignant transformation risk markers in potentially malignant disorders (PMDs) of ...the head and neck.
Material and Methods
We searched PubMed, Embase, Web of Science, and Scopus for studies published before June 2018. We conducted a meta‐analysis to quantify the impact of CCND1/cyclin D1 amplification/overexpression on malignant transformation of head and neck PMDs.
Results
Nine studies met inclusion criteria. Quantitative evaluation indicated strong statistically significant association between CCND1/cyclin D1 amplification/overexpression and the progression of head and neck PMD to head and neck squamous cell carcinoma (risk ratio RR = 2.04, 95% confidence interval CI = 1.37‐3.03, P < .001, and RR = 2.27, 95% CI = 1.32‐3.91, P = .003, respectively). We observed moderate heterogeneity among studies (I2 = 40.7%), and we cannot rule out small‐study effects such as publication bias. The oral cavity subgroup showed the strongest association between CCND1/cyclin D1 amplification/overexpression and progression to cancer.
Conclusion
CCND1/cyclin D1 amplification/overexpression is important to predict the malignant transformation risk of head and neck PMDs, especially oral PMDs.
Background
To evaluate the prognostic significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma (HNSCC).
Material and methods
We searched PubMed, Embase, Web of Science, and ...Scopus for studies published before May 2018. We conducted a meta‐analysis to quantify the impact of CTTN/cortactin alterations on clinicopathological and survival variables.
Results
Eighteen studies (1633 patients) met inclusion criteria. Quantitative evaluation revealed a strong association of CTTN/cortactin alterations with N+ status (P < .001), higher T status (P < .001), advanced clinical stage (P < .001), high histological grade (P = .001), and lower overall survival (OS) (P < .001). We found heterogeneity in T status, histological grade, and OS and observed small‐study effects on N status and OS. In subgroup analyses, a significant association of CTTN amplification and cortactin overexpression with the above variables was preserved. The strongest association between CTTN/cortactin alterations and a worse outcome was observed in the subgroups of Asian patients and pharyngolaryngeal squamous cell carcinomas.
Conclusions
CTTN/cortactin alterations should be evaluated to predict the HNSCC prognosis.
Background
The association between low bone mineral density (BMD) and periodontitis in perimenopausal women is controversial. The purpose of this study was to determine whether osteoporosis or ...osteopenia is associated with periodontal disease in a population of adult women.
Methods
A sample of over‐45‐year‐old women with or without low BMD underwent lumbar spine and hip bone densitometry and a complete periodontal examination. The extent/severity or absence of periodontal disease was noted using two different case definitions. Data were gathered on socio‐economic status, medication history, systemic co‐morbidities, alcohol or tobacco use as well as serum levels of calcium and vitamin D.
Results
One hundred seventy three women aged between 45 and 72 years old were recruited with a mean age of 57.8 years. One hundred and three had decreased BMD (61 with osteoporosis and 42 with osteopenia) and 70 were healthy. Moderate or severe periodontitis was present in 52.6% of the women. Multivariate analysis showed a clear association between low BMD and periodontitis, but only in women above 58 years old and independent of tobacco consumption or oral hygiene.
Conclusion
In this sample of generally healthy perimenopausal women, low BMD was associated with clinical attachment level (CAL). Women over 58 years old with decreased BMD presented with a higher mean percentage of sites with CAL ≥ 4 mm as well as CAL ≥ 6 mm when compared to controls, independent of active smoking status or poor oral hygiene.
•We analyzed the prognostic value of CD1 in 31 studies and 2942 patients with OSCC.•CD1 overexpression is associated with poor survival, T and N status, clinical stage, and histological grade.•CD1 ...overexpression has greater prognostic impact on patients with tongue SCC.•The ideal cutoff point for the evaluation of CD1 overexpression is ≥10% CD1-positive tumor cells.•Current evidence indicates that CD1 may be used as prognostic biomarker in OSCC.
To evaluate the prognostic significance of cyclin D1 (CD1) overexpression in OSCC.
We searched studies published before August 2017 (Pubmed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (Quality in Prognosis Studies QUIPS tool). The impact of CD1 overexpression on overall survival and disease-free survival, T status, N status, stage, and histological degree was meta-analyzed. We analyzed heterogeneity among studies, conducted sensitivity analyses, analyzed small-study effects, and conducted subgroup analyses.
31 studies (2942 patients) met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that CD1 overexpression had a strong statistical association with worse overall survival (HR = 2.00, 95% CI = 1.59–2.51, p < 0.001), worse disease-free survival (HR = 1.46, 95% CI = 1.13–1.87, p = 0.003), higher T status (OR = 1.51, 95% CI = 1.07–2.13, p = 0.02), N+ status (OR = 2.16, 95% CI = 1.60–2.92, p < 0.001), advanced stage (OR = 1.44, 95% CI = 1.15–1.81, p = 0.002), and high histological grade (OR = 1.60, 95% CI = 1.12–2.29, p = 0.010). We observed heterogeneity in all parameters except for disease-free survival and clinical stage. We found effect of small studies on T and N status. The tonguel SCC subgroup showed the strongest association between CD1 overexpression and worse development. In addition, application of a cutoff point ≥10% tumor cells with nuclear CD1 expression maintained most of the significant associations reported.
These findings indicate that immunohistochemical assessment of CD1 overexpression may be useful as a prognostic biomarker for OSCC.
Cortactin is a protein encoded by the CTTN gene, localized on chromosome band 11q13. As a result of the amplification of this band, an important event in oral carcinogenesis, CTTN is also usually ...amplified, promoting the frequent overexpression of cortactin. Cortactin enhances cell migration in oral cancer, playing a key role in the regulation of filamentous actin and of protrusive structures (invadopodia and lamellipodia) on the cell membrane that are necessary for the acquisition of a migratory phenotype. We also analyze a series of emerging functions that cortactin may exert in oral cancer (cell proliferation, angiogenesis, regulation of exosomes, and interactions with the tumor microenvironment). We review its molecular structure, its most important interactions (with Src, Arp2/3 complex, and SH3‐binding partners), the regulation of its functions, and its specific oncogenic role in oral cancer. We explore the mechanisms of its overexpression in cancer, mainly related to genetic amplification. We analyze the prognostic implications of the oncogenic activation of cortactin in potentially malignant disorders and in head and neck cancer, where it appears to be relevant in the development of lymph node metastasis. Finally, we discuss its usefulness as a therapeutic target and suggest future research lines.
We have previously reported that the negative signaling regulator Similar Expression to FGF (hSef) is downregulated in prostate cancer and its loss is associated with clinical metastasis. Here, we ...explored the mechanistic basis of this finding. We first confirmed our clinical observation by testing hSef manipulation in an in vivo metastasis model. hSef stable expressing cells (PC3M‐hSef) or empty vector controls (PC3M‐EV) were injected subcutaneously into the lateral thoracic walls of NOD‐SCID gamma mice and lungs were harvested at autopsy. In this model, 6/7 PC3M‐EV xenografts had definitive lung micro‐metastasis whilst only 1/6 PC3M‐hSef xenografts exhibited metastasis recapitulating the clinical scenario (p = 0.03). Gene expression studies revealed key perturbations in genes involved in cell motility and epithelial to mesenchymal transition (EMT) along with alterations in cognate signaling pathways. These results were validated in an EMT specific PCR array whereby hSef over‐expression and silencing reciprocally altered E‐Cadherin expression (p = <0.001) amongst other EMT markers. Immunohistochemistry of excised tumors from the xenografts also confirmed the effect of hSef in suppressing E‐Cadherin expression at the protein level. Phosphokinase arrays further demonstrated a role for hSef in attenuating signaling of not only ERK‐MAPK but also the JNK and p38 pathways as well. Taken together, these data suggest evidence that loss of hSef may be a critical event facilitating tumor dissemination of prostate cancer through alteration of EMT. Detection of downregulated hSef, along with other negative regulators, may therefore be a useful biomarker heralding a transition to a metastatic phenotype and warrants further exploration in this context.
What's new?
The loss of negative signaling regulators may be implicated in prostate cancer metastasis, but the underlying mechanisms remain unclear. Here, by using a combination of xenograft, gene expression microarray, phosphokinase array and quantitative PCR techniques, the authors provide first evidence that the negative regulator hSef plays a key role in regulating epithelial to mesenchymal transition (EMT) in prostate cancer, which in turn results in changes in the metastatic ability of tumor cells. The results support the notion that the expression levels of hSef and other negative signaling regulators may be key biomarkers for the identification of triggers for metastasis.
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