[ca] 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).

[en] 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.