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Simple Summary: The incidence of cutaneous melanoma is increasing worldwide, currently responsible for 287,723 new cases and 60,712 deaths per year (GLOBOCAN, IARC, WHO). It should be also highlighted that some less frequent subtypes of melanomas—i.e., acral, uveal, and mucous melanoma—are responsible for significant morbidity associated with metastasis, responding typically worse to newer therapies. Therefore, new biomarkers are needed to improve the prognosis in individual patients. In this sense, the present study showed that CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion on cutaneous primary melanomas. Furthermore, immunohistochemical cyclin D1 overexpression strongly predicted a higher Breslow thickness, currently considered the most relevant prognostic factor in individual patients with melanomas. Finally, special attention should be paid to the CCND1/cyclin D1 complex in mucosal melanomas, whose upregulation was strikingly altered. Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 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 immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23–3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40–0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01–2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification. [ABSTRACT FROM AUTHOR]

The objective was to assess the global oral lichen planus prevalence. We searched PubMed, EMBASE, Web of Science, and Scopus for studies published before September 2019. We evaluated the quality of studies and carried out several meta‐analyses. The global pooled prevalence was 1.01%, with a marked geographical difference (p <.001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco‐associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40 years, the prevalence increases significantly and progressively (OR = 3.43, 95% CI = 2.48–4.73, p <.001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%, p =.03), although the application of the WHO criteria (year 1978‐2007) does not increase the ability to diagnose the disease compared with other criteria (p =.11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%; p <.001). In conclusion, we propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta‐analysis. [ABSTRACT FROM AUTHOR]

Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aims to evaluate the clinicopathological and prognostic significance of FADD upregulation in HNSCC. We searched studies published before February 2020 through PubMed, Embase, Web of Science, Scopus and Google Scholar. We evaluated the quality of the studies included using the QUIPS tool. The impact of FADD upregulation on survival and clinicopathological variables was meta-analysed. We explored heterogeneity and their sources, conducted sensitivity analyses and investigated small-study effects. Thirteen studies (1,923 patients) met inclusion criteria. FADD immunohistochemical overexpression was statistically associated with worse overall survival (hazard ratio [HR] = 1.52, 95% confidence intervals [CI] = 1.28–1.81, p < 0.001), disease-specific survival (HR = 2.52, 95% CI = 1.61–3.96, p < 0.001), disease-free survival (HR = 1.67, 95% CI=1.29–2.15, p < 0.001), higher clinical stage (odds ratio [OR] = 1.72, 95% CI = 1.17–2.51, p = 0.005) and a large magnitude of effect with N+ status (OR = 2.36, 95% CI = 1.85–3.00, p < 0.001). FADD phosphorylation in ser-194 demonstrated no prognostic value, while no conclusive results can be drawn for FADD gene amplification. In conclusion, our findings indicate that immunohistochemical assessment of FADD overexpression could be incorporated into the prognostic evaluation of HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate current evidence in relation to the prognostic and clinicopathological significance of oral squamous cell carcinomas arising in patients with oral lichen planus (OLP-OSCC).Material and Methods: We searched PubMed, Embase, Web of Science and Scopus for studies published before May-2019. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objective. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity and subgroup analyses.Results: Inclusion criteria were met by 27 studies (10,505 patients with OLP, of whom 205 developed a total of 247 OSCCs). The combined 5-year mortality rate was 15.48% for OLP-OSCC (95%CI  =  7.34-25.19), clearly lower than the 34.70-50.00% mortality rate for conventional oral cancer communicated in previous official reports. Also, 14.67% (95%CI  =  6.34-24.81) of OLP-OSCC developed N+ status, compared to 47.00% of conventional oral carcinomas. Likewise, most of the OSCCs in the study were T1/T2 (93.57%, 95%CI  =  82.20-99.88) and presented at stage I/II (81.51%, 95%CI = 68.32-92.38) at the time of diagnosis, which contrasts with 50.00% of conventional carcinomas diagnosed in stages I/II. Furthermore, most of the cases were grade I (well differentiated OSCC) (67.79%; 95%CI = 43.50-88.65), in comparison to conventional OSCCs, which present typically in grade II in 90.00% of cases. Our results also show an 11.21% of the OLP-OSCC patients in this study developed multiple tumors.Conclusions: Oral squamous cell carcinomas that developed in oral lichen planus show favorable prognostic parameters, especially with regard to the mortality rate. Around 11% of OLP-OSCC patients develop multiple tumors, which confirms that OLP can lead to field cancerization. [ABSTRACT FROM AUTHOR]