Neurofibromin Expression is Associated with Aggressive Disease and Poor Outcome in Colorectal Carcinoma

Abstract

Abstract. Aim: To assess the predictive and prognostic value of neurofibromin (NF) expression in colorectal carcinoma (CRC). Materials and Methods: The present series consists of archival samples from 191 patients with stage I, II, III, or IV CRC treated between 1981 and Colorectal cancer (CRC) is the third most common cancer in the world, also ranking as the third most common cause of cancer-related deaths (1). Despite the fact that most CRC patients undergo potentially curative surgery and adjuvant chemotherapy administered, approximately 50% of all patients initially considered curable by surgery, will subsequently relapse and die of their disease (2).The etiology of CRC remains open and the overall outcome is poor (3). However, some fundamental advances in our understanding of the biology and genetics of CRC have been made recently (4-5).CRC arises from progressive accumulation of genetic and epigenetic changes (e.g. chromosomal instability, microsatellite instability and methylation pathway that cause the transformation of normal colon mucosa cells into adenocarcinoma (6, 7).Alterations in NF1 gene mutations and neurofibromin (NF) expression have been found in colon adenocarcinoma, myelodysplastic syndrome, anaplastic astrocytoma and small-cell lung carcinoma (8-9). NF, the protein encoded by NF1 gene, is a cytoplasmic protein predominantly expressed in neurons, Schwann cells, oligodendrocytes and leucocytes (10). It functions as a GTPase, activating protein (GAP) for Ras by accelerating the conversion of active Ras-GTP to inactive 12). NF acts as a negative regulator of the Ras/mitogen-activated protein kinase signaling pathway via suppression of active Ras (13). Therefore, the negative regulation of Ras activity classifies NF1 gene as a tumor suppressor gene.To date, little is known about the role of tumor suppressor NF in CRC, and data on its potential prognostic value in these tumors are lacking. In this study, we examined the expression of NF in 191 CRCs using immuno-histochemistry 5301

Comparative Analysis of Putative Prognostic and Predictive Markers in Neuroblastomas: High Expression of PBX1 Is Associated With a Poor Response to Induction Therapy

“…As all the patients in our cohort were diagnosed with high-risk NBL, all of our results on NF1 correspond to the hypothesis on the relationship between NF1 overexpression associated with aggressive tumor behavior. Similar findings were recently published for colorectal carcinoma (29).…”

oss of CDX2 and high COX2 (PTGS2) expression in metastatic colorectal cancer

“…Similar to their CRC samples, we had nearly 80% of the samples with moderate (score 2) to strong (score 3) staining intensity (Figure 3). While in other series, COX2 expression was not significantly different among tumour grades [12,47], a significant enrichment of poorly differentiated tumours was observed among COX2-negative samples in our study. Different studies reported higher OS rates among CRC patients whose tumours are negative for COX2 protein [24,28,30,36,47,59].…”

Inflammatory gene mRNA expression in human peripheral blood and its association with colorectal cancer

“…Prostaglandins (PGs) play a predominant role in cancer development through promoting cell proliferation, invasion, angiogenesis and immunosuppression. 10 The COX-2-regulated synthesis of PGs, particularly PGE-2, causes various types of cancers including CRC. 11 COX-2 gene is highly expressed in 85% of adenocarcinoma cases with a poor survival rate.…”