Estudi de les alteracions genètiques i moleculars implicades en el carcinoma escatós oral

L’oncogènesi en la cavitat oral és deguda a l’acumulació d’alteracions genètiques, epigenètiques i metabòliques, que ocasionen un procés de transformació gradual des d’una mucosa oral normal a una mucosa displàsica, i posteriorment a un carcinoma escatós invasiu, normalment com a resultat de l’exposició a diversos factors ambientals (begudes alcohòliques, tabac, virus del papil·loma humà, etc.). El nombre d’alteracions cromosòmiques sembla que augmentaria durant la progressió del càncer. S’han descrit diferents alteracions citogenètiques en el carcinoma escatós oral (CEO) que inclouen anormalitats del cromosoma Y, l’activació de proto-oncogens com ciclina D1 (CCND1), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuro/glioblastoma derived oncogene homolov-myc myelocytomatosis viral oncogene homolog (MYC), RAS p21 protein activator (RAS), epidermal growth factor receptor (EGFR) i la inactivació de gens supressors tumorals com cyclin-dependent kinase inhibitor 2A (CDKN2A) i tumor protein p53 (TP53). L’objectiu de l’estudi que presentem és la descripció de les alteracions genètiques i d’expressió proteica de CCND1, MYC, EGFR, CKS1B, ERBB2 i el supressor tumoral TP53 en mostres de CEO i metàstasis ganglionars i comparar-ho amb mucosa oral sana, amb lesions inflamatòries orals (liquen pla oral [LPO]) i lesions pre-malignes com la leucoplàsia oral (LKO).The oncogenesis in the oral cavity is due to the accumulation of genetic, epigenetic and metabolic alterations that cause a gradual transformation from a normal oral mucosa to dysplastic mucosa, and subsequently to invasive squamous cell carcinoma, usually as a result of exposure to various environmental factors (alcohol, tobacco, human papilloma virus). The number of chromosomal abnormalities appears to increase during the progression of the illness. Different cytogenetic abnormalities have been described in oral squamous cell carcinoma (OSCC) that include the activation of proto-oncogenes such as cyclin D1 (CCND1), v-erb-b2 erythroblastic leukemia viral oncogene 2 (ERBB2) , neuro / glioblastoma derived Oncogene homolov-myc myelocytomatosis viral oncogene (MYC), RAS p21 protein activator (RAS), epidermal growth factor receptor (EGFR) and inactivation of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A (CDKN2A) and tumor protein p53 (TP53). The aim of the herein study is the description of the genetic alterations and proteic status of CCND1, MYC, EGFR, CKS1B, ERBB2 and TP53 in OSCC and lymph node metastatic samples, and to compare it with healthy oral mucosa, oral inflammatory lesions (oral lichen planus [OLP]) and pre-malignant lesions such as oral leukoplakia (OLK). Methods We included 108 samples corresponding to 14 biopsies of normal oral mucosa, 51 samples of OSCC, 14 lymph node metastases, 13 OLP and 16 OLK, with which we have constructed two tissue microarrays (TMA). We collected clinical and pathological variables of each case. We performed immunohistochemical stains and fluorescent in situ hybridization (FISH) markers of interest. Results The first paper includes the findings by FISH and immunohistochemistry of the oncogenes and suppressor genes CCDN1, MYC, EGFR, ERBB2 and TP53. We found polisomies and amplifications of the oncogenes and losses of TP53 in a proportion significantly higher in samples of primary and metastatic OSCC, with correlation with the expression of their protein products. The presence of two or more genetic abnormalities in the studied loci was only found in OSCC primary and metastatic samples. The second paper describes the genetic and proteic status of CKS1B. It appears significantly overexpressed in primary and metastatic OSCC samples, which correlates with the infraexpression of p27 and overexpression of SKP2. The study also shows gains by FISH (polisomies and amplifications) of 1q21. Conclusions This study shows that the increased expression of several molecular markers can occur in all stages of oral cancer. The genetic aberrations detected by FISH were frequently observed in malignant lesions, rarely in OLK and iexceptionally rare in benign inflammatory samples. This supports the role of CKS1B, MYC, TP53, CCDN1, ERBB2 and EGFR in the pathogenesis of the CEO. Thus, OSCC samples accumulate more aberrations than pre-malignant and benign samples, both in the genetic and proteic level, which remains in agreement with the literature. This is indicative of the chromosomal instability that characterizes these solid tumors

Estudi de les alteracions genètiques i moleculars implicades en el carcinoma escatós oral

L'oncogènesi en la cavitat oral és deguda a l'acumulació d'alteracions genètiques, epigenètiques i metabòliques, que ocasionen un procés de transformació gradual des d'una mucosa oral normal a una mucosa displàsica, i posteriorment a un carcinoma escatós invasiu, normalment com a resultat de l'exposició a diversos factors ambientals (begudes alcohòliques, tabac, virus del papil·loma humà, etc.). El nombre d'alteracions cromosòmiques sembla que augmentaria durant la progressió del càncer. S'han descrit diferents alteracions citogenètiques en el carcinoma escatós oral (CEO) que inclouen anormalitats del cromosoma Y, l'activació de proto-oncogens com ciclina D1 (CCND1), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuro/glioblastoma derived oncogene homolov-myc myelocytomatosis viral oncogene homolog (MYC), RAS p21 protein activator (RAS), epidermal growth factor receptor (EGFR) i la inactivació de gens supressors tumorals com cyclin-dependent kinase inhibitor 2A (CDKN2A) i tumor protein p53 (TP53). L'objectiu de l'estudi que presentem és la descripció de les alteracions genètiques i d'expressió proteica de CCND1, MYC, EGFR, CKS1B, ERBB2 i el supressor tumoral TP53 en mostres de CEO i metàstasis ganglionars i comparar-ho amb mucosa oral sana, amb lesions inflamatòries orals (liquen pla oral [LPO]) i lesions pre-malignes com la leucoplàsia oral (LKO).The oncogenesis in the oral cavity is due to the accumulation of genetic, epigenetic and metabolic alterations that cause a gradual transformation from a normal oral mucosa to dysplastic mucosa, and subsequently to invasive squamous cell carcinoma, usually as a result of exposure to various environmental factors (alcohol, tobacco, human papilloma virus). The number of chromosomal abnormalities appears to increase during the progression of the illness. Different cytogenetic abnormalities have been described in oral squamous cell carcinoma (OSCC) that include the activation of proto-oncogenes such as cyclin D1 (CCND1), v-erb-b2 erythroblastic leukemia viral oncogene 2 (ERBB2) , neuro / glioblastoma derived Oncogene homolov-myc myelocytomatosis viral oncogene (MYC), RAS p21 protein activator (RAS), epidermal growth factor receptor (EGFR) and inactivation of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A (CDKN2A) and tumor protein p53 (TP53). The aim of the herein study is the description of the genetic alterations and proteic status of CCND1, MYC, EGFR, CKS1B, ERBB2 and TP53 in OSCC and lymph node metastatic samples, and to compare it with healthy oral mucosa, oral inflammatory lesions (oral lichen planus [OLP]) and pre-malignant lesions such as oral leukoplakia (OLK). Methods We included 108 samples corresponding to 14 biopsies of normal oral mucosa, 51 samples of OSCC, 14 lymph node metastases, 13 OLP and 16 OLK, with which we have constructed two tissue microarrays (TMA). We collected clinical and pathological variables of each case. We performed immunohistochemical stains and fluorescent in situ hybridization (FISH) markers of interest. Results The first paper includes the findings by FISH and immunohistochemistry of the oncogenes and suppressor genes CCDN1, MYC, EGFR, ERBB2 and TP53. We found polisomies and amplifications of the oncogenes and losses of TP53 in a proportion significantly higher in samples of primary and metastatic OSCC, with correlation with the expression of their protein products. The presence of two or more genetic abnormalities in the studied loci was only found in OSCC primary and metastatic samples. The second paper describes the genetic and proteic status of CKS1B. It appears significantly overexpressed in primary and metastatic OSCC samples, which correlates with the infraexpression of p27 and overexpression of SKP2. The study also shows gains by FISH (polisomies and amplifications) of 1q21. Conclusions This study shows that the increased expression of several molecular markers can occur in all stages of oral cancer. The genetic aberrations detected by FISH were frequently observed in malignant lesions, rarely in OLK and iexceptionally rare in benign inflammatory samples. This supports the role of CKS1B, MYC, TP53, CCDN1, ERBB2 and EGFR in the pathogenesis of the CEO. Thus, OSCC samples accumulate more aberrations than pre-malignant and benign samples, both in the genetic and proteic level, which remains in agreement with the literature. This is indicative of the chromosomal instability that characterizes these solid tumors

Pruritic nodular secondary syphilis in a 61-year-old man with HIV infection

The typical finding in secondary syphilis stage is a generalized non-pruritic maculopapular eruption. We report a case of secondary syphilis in an HIV-infected patient presenting with pruritic crusted nodules showing numerous eosinophils on the histopathological examinatio

Persistent cutaneous abdominal ulcerations secondary to diffuse dermal angiomatosis: an underestimated sign for severe atherosclerosis: A case report.

BACKGROUND: Diffuse dermal angiomatosis (DDA) is a rare, acquired, reactive vascular proliferation, clinically characterized by livedoid erythematous-violaceous plaques, which frequently evolve to ulceration and necrosis. Histopathologically, it is manifested by a diffuse proliferation of endothelial cells within the full thickness of the dermis. DDA has been mainly associated with severe peripheral atherosclerosis. METHODS: We report a 63-year-old woman who presented with multiple erythematous-violaceous plaques with central deep skin ulcers on thighs, lower abdomen, and perianal area, associated with intermittent claudication, low-grade fever, and weight loss. Initially, the clinical picture along with positive cultures for Klebsiella pneumoniae suggested a multifocal ecthyma gangrenosum; nevertheless, a skin biopsy showed a diffuse dermal proliferation of endothelial cells interstitially arranged between collagen bundles. A computed tomography scan revealed severe aortic atheromatosis with complete luminal occlusion of the infrarenal aorta and common iliac arteries. RESULTS: The diagnosis of DDA secondary to severe atherosclerosis was established. The patient underwent a left axillofemoral bypass surgery with a rapidly healing of the ulcers in the next weeks./nCONCLUSIONS: DDA should be considered in the differential diagnosis of livedoid ischemic lesions. Recognition of DDA as a cutaneous sign of severe peripheral vascular disease is important for both dermatologists and internists. Recognition of risk factors and their management with an early intervention to correct tissue ischemia can be curative

CDC28 protein kinase regulatory subunit 1B (CKS1B) expression and genetic status analysis in oral squamous cell carcinoma

CKS1B is a member of the highly conserved cyclin kinase subunit 1 (CKS1) protein family which interacts with cyclin-dependent kinases and plays a critical role in cell cycle progression. In oral squamous cell carcinoma (OSCC), as in other malignancies, CKS1B overexpression has been correlated with reduced survival. To our knowledge, no studies evaluating the genetic status of CKS1B gene in OSCC have been reported. Herein, genetic and protein status of CKS1B were analyzed by immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) techniques in a series of primary OSCC (n=51) and lymph node OSCC metastases samples (n=14). The observed results were compared with those obtained in either inflammatory (oral lichen planus [OLP]) (n=13) and premalignant oral mucosal lesions (oral leukoplakia) (n=16). A significant CKS1B overexpression was observed in OSCC and lymph node metastases samples than in OLP and oral leukoplakia (mean 70% vs 35%, p<0.001). CKS1B overexpression correlated with p27 loss of expression (p=0.0013) and SKP2 overexpression (p<0.00). FISH study disclosed statistical differences in both gene amplifications and gains between samples corresponding to OSCC and metastases from those of OLP and leukoplakia (p<0.001). Amplifications were present in 53% of OSCC samples and 33% of lymph node metastases vs 14% of oral leukoplakia and 0% of OLP biopsy specimens (p=0.002). Polysomies of chromosome 1 were seen in 46% of OSCC, 33% of ganglionar metastases, 14% of oral leukoplakia and 10% of OLP (p=0.036). Correlation of CKS1B overexpression and gains (both polysomies and amplifications) determined by FISH was statistically significant (p<0.001). Our results indicate that a high CKS1B expression is a common finding in primary OSCC which correlates with p27 low expression and SKP2 overexpression. This phenomenon may be due either to numerical (chromosome 1 polysomy) or structural (amplifications) CKS1B genetic abnormalities. This phenotypical and cytogenetic profile is not observed in premalignant or inflammatory oral mucosal lesions

Monkeypox outbreak in Spain: clinical and epidemiological findings in a prospective cross-sectional study of 185 cases.

Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports. To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak. We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak. In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in men who have sex with men and are strongly associated with high-risk sexual behaviours. Seventy-six per cent of the patients had other sexually transmitted diseases upon screening. The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterization of the epidemiology of this outbreak has implications for control. What is already known about this topic? Monkeypox eruption is described as consisting of pustules. The roles of HIV and previous smallpox vaccination in the prognosis are unknown. The transmission route was initially described as respiratory droplets and was later suggested to be via sexual contact. What does this study add? Initial lesions at the probable inoculation area were homogeneous and papular (pseudopustules). Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common signs included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Well-controlled HIV and previous smallpox vaccination were not associated with severity. No patient died. The data support the hypothesis of transmission via contact during sex. Although this might change, the outbreak is currently limited mostly to men who have sex with men, with high-risk factors for sexually transmitted diseases