c-Fos/ c-Jun transcription factors in non-small cell lung carcinoma.

During lung carcinoma development, progression and metastasis, a variety of gross (chromosome) and specific (gene) genomic alterations are detected in dysplastic, neoplastic, and progressively malignant transformed epithelia as early or late genetic events. Oncogenes' overactivation combined with suppressor genes silence are crucial genetic events in malignant and pre-malignant epithelia. Especially, deregulation of crucial signalling transduction pathways that interact with strong transcription factors - such as c-Fos and c-Jun - leads to an aberrant expression of other critical genes responsible for cell homeostasis. Upregulation of c-Fos and c-Jun leading to other oncogenes overactivation seems to be correlated with aggressive biological behaviour in non-small cell lung carcinomas (NSCLCs). In the current special molecular article we explored the role of c-Fos/c-Jun complex deregulation in NSCLC based on their interactions with other genes that demonstrate modified expression profiles.

Replication Protein A (RPA1, RPA2 and RPA3) expression in gastric cancer: correlation with clinicopathologic parameters and patients' survival.

PURPOSE: Replication Protein A (RPA) consists of three subunits (RPA1, RPA2 and RPA3) essential for all major DNA metabolic pathways. Although RPA seems to be a promising therapeutic target, its role in human cancers has not been fully elucidated. This is the first study investigating the expression of all the three RPA subunits in a series of 74 resected gastric carcinomas and analyzing the possible correlations with clinicopathologic parameters (histological type, grade, lymphovascular invasion, lymph node status and disease stage), Ki-67 proliferative index, Topoisomerase IIa expression and patients' survival. METHODS: Immunohistochemistry using monoclonal antibodies. Univariate and multivariate statistical analysis. RESULTS: All the three subunits showed widespread nuclear expressions in gastric carcinomas with significant associations among their expressions. RPA2 demonstrated higher expression levels in low grade carcinomas and a gradual significant decrease from N0 to N3 and from stage I to stage IV carcinomas. All the three subunits were statistical significantly more abundant in lymph node negative and earlier stage (stage I & II) gastric carcinomas. No associations were established among RPAs and the proliferative marker Ki-67. In patients with positive lymph nodes and advanced tumor stage, RPA1 expression seemed to predict a better overall survival implying a probable predictive role. CONCLUSIONS: The widespread expression of RPA(1-3) suggests one or more roles in gastric cancer. Their presence in earlier stage tumors probably offers an opportunity for early targeted therapy. Their probable predictive value in node positive and advanced stage tumors needs further investigation with respect to specific chemotherapeutic treatments.