RESUMEN
Unknown primary tumors (UPTs) represent an entity of great clinical and biological interest, whose origin cannot be determined even after medical workup. To better understand their pathogenesis by outlining their genetic composition, 20 UPTs were investigated by G-banding, supplemented with Fluorescence In Situ Hybridization and Comparative Genomic Hybridization analyses. The data obtained were sufficient to reach a diagnosis in five cases-four lymphomas and one Ewing sarcoma-demonstrating that in a subset of UPTs, cytogenetics can be an adjunct for differential diagnosis. In the remaining 15 UPTs, an aggressive cytogenetic pattern was revealed. The most frequently rearranged chromosome regions were 1q21, 3p13, 6q15-23, 7q22, 11p12-5, and 11q14-24, pinpointing gene loci probably associated with the peculiar pathogenesis of UPTs. The preferential involvement of 4q31, 6q15, 10q25, and 13q22 in adenocarcinomas (whereas 11q22 is involved in the rest of the carcinomas)-in addition to the marked divergence in the mean average of chromosomal changes, 16 and 3, respectively-demonstrates genotypic differences between the two histologic subgroups. Furthermore, the significantly shorter survival in cases displaying massive chromosome changes compared with those having a few changes indicates that the cytogenetic pattern might be used as a tool to assess prognosis in UPTs, even without the detection of their primary site.
Asunto(s)
Adenocarcinoma/genética , Aberraciones Cromosómicas , Bandeo Cromosómico , Hibridación Fluorescente in Situ , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/genética , Hibridación de Ácido Nucleico , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Adolescente , Adulto , Anciano , Citogenética , Diagnóstico Diferencial , Femenino , Humanos , Interfase , Cariotipificación , Masculino , Metafase , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/patología , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
The coding region determinant-binding protein (CRD-BP) is an RNA binding protein that recognizes c-myc and IGF-II leader 3 mRNAs as well as the oncofetal H19 RNA. CRD-BP exhibits an oncofetal pattern of expression and has been detected in the majority of colon (81%), breast (58.5%) and sarcoma (73%) tumors. The study of CRD-BP expression was extended in brain tumors and Non small cell lung (NSCL) carcinomas and 12/24 malignant, 2/5 benign neuroepithelial tumors and 4/15 of NSCL carcinomas were found positive. All normal matching tissues tested were found negative. The highest frequency (60%) of CRD-BP positive tumors was observed in meningiomas, either benign (11/18) or atypical (3/3). These findings confirm that CRD-BP expression is restricted in tumors; the frequency of its de novo expression may vary according to tumor type and appears to be an early event in the transformation process.