Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer.

The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrP(C)-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression. We have previously reported that expression levels of PRNP may have a prognostic value in CRC, suggesting a role for the prion protein in CRC. The aim of this study was to investigate retrospectively the possible role of M129V and PrP(C) expression in patients with CRC. The M129V single nucleotide polymorphism was genotyped by real time polymerase chain reactions in 110 patients with CRC and 124 healthy donors. Moreover, protein expression was assessed by immunohistochemistry in 68 patients with CRC. Allele frequencies were similar in patients and healthy controls indicating that the M129V polymorphism is not a risk factor for CRC. Furthermore, it did not correlate with any clinicopathological parameters. By contrast, PrP(C) expression was highly elevated in neoplastic compared to normal tissue and differed depending on the primary site. Interestingly, protein levels were correlated with disease recurrence (P = 0.007). Conclusively, PrP(C) overexpression may constitute a prognostic marker for disease recurrence and potentially a new target for anticancer therapy. However, further studies are needed to evaluate prospectively the role of PrP(C) expression in patients with CRC.

Early-Stage Breast Cancer in the Elderly: Confronting an Old Clinical Problem.

Breast cancer generally develops in older women and its incidence is continuing to increase with increasing age of the population. The pathology and biology of breast cancer seem to be different in the elderly, often resulting in the undertreatment of elderly patients and thus in higher rates of recurrence and mortal-ity. The aim of this review is to describe the differences in the biology and treatment of early breast cancer in the elderly as well as the use of geriatric assessment methods that aid decision-making. Provided there are no contraindications, the cornerstone of treatment should be surgery, as the safety and efficacy of surgical resection in elderly women have been well documented. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant setting. The role of chemotherapy is limited to patients who test negative for hormone receptors and demonstrate an aggressive tumor profile. Although the prognosis of breast cancer patients has generally improved during the last few decades, there is still a demand for evidence-based optimization of therapeutic interventions in older patients.

Altered expression of NFY-C and RORA in colorectal adenocarcinomas.

NFY-C, a subunit of the transcription factor NFY, binds to the promoters of several eukaryotic genes, including cell cycle-related genes. RORA is a steroid hormone receptor implicated in a range of important cellular processes. We evaluated the expression of NFY-C and RORA in colorectal adenocarcinomas and normal colonic tissue. NFY-C expression was elevated in adenocarcinomas. Moreover, NFY-C mRNA levels correlated with time to disease progression, while NFY-C protein expression was significantly higher in metastatic disease. RORA expression was downregulated in CRC adenocarcinomas compared to normal controls and correlated with time to disease progression. The role of NFY-C and RORA in CRC merits further investigation.

NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although our knowledge on the pathobiology of the disease has increased in the last decades, the prognosis of lung cancer patients has hardly changed. Many signaling pathways are implicated in lung carcinogenesis, but the role of the alternative pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung cancer pathogenesis and progression has not been investigated. The aim of our study was to investigate the role of this pathway in non-small cell lung cancer (NSCLC) patients. NF-κB2 and RelB protein expression was retrospectively assessed by immunohistochemistry in tissue samples from 109 NSCLC patients. RelB and NF-κB2 protein levels differed between tumors and adjacent nonneoplastic lung parenchyma. Cytoplasmic immunoreactivity of NF-κB2 and RelB was correlated with tumor stage (p = 0.03 and p = 0.016, respectively). In addition, cytoplasmic NF-κB2 levels were related to tumor grade (p = 0.046). Expression of RelB in the cytoplasm was tumor histologic type-specific, with squamous cell carcinomas having the highest protein levels. Nuclear expression of RelB and NF-κB2 differed between tumor and nonneoplastic tissues, possibly indicating activation of the alternative pathway of NF-κB in cancer cells. Moreover, lymph node metastasis was related to nuclear NF-κB2 expression in tumor cells. The deregulation of the alternative NF-κB pathway in NSCLC could play a role in the development and progression of the disease.

VEGF polymorphisms may be associated with susceptibility to colorectal cancer: a case-control study.

The vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis. VEGF levels appear to be influenced by single nucleotide polymorphisms (SNPs) of the VEGF gene. The aim of this study was to assess the importance of four VEGF SNPs in modulating susceptibility to colorectal cancer. We have genotyped 223 patients with colorectal cancer and 264 healthy individuals for the -2578C>A, -1498C>T, -634G>C and +936C>T VEGF SNPs using Taqman probes in polymerase chain reactions. The -2578 A, -1498 C and -634 G alleles were more frequently detected in CRC patients compared to healthy controls. Moreover, the haplotype -2578C/-1498T was less frequent in CRC patients while the -2578A/-1498C haplotype was significantly more frequent in patients compared to healthy controls. VEGF -2578C>A and -1498C>T SNPs and -2578/-1498 haplotypes appear to be associated with susceptibility to CRC.

Association of FOXP3 expression with non-small cell lung cancer.

BACKGROUND/AIM: Lung cancer is rarely cured by current therapeutic approaches. Although numerous studies have implicated FOXP3 positive regulatory T-cells in cancer pathogenesis, the role of FOXP3 in lung cancer pathogenesis remains unkown. MATERIALS AND METHODS: Using immunohistochemistry FOXP3 expression was determined in 44 NSCLC tissue specimens, 20 samples from adjacent non neoplastic lung parenchyma and 5 normal lung tissue specimens. RESULTS: FOXP3 immunostaining was always nuclear in both tumor and non-neoplastic adjacent tissues. FOXP3 was also detected at lower levels in normal bronchial epithelium. Moreover, FOXP3 expression in cancer cells correlated with lymphocytic FOXP3-immunopositivity and the presence of lymph node metastasis. FOXP3 lymphocytic expression was also negatively associated with the age of the patients. CONCLUSION: FOXP3 is overexpressed in NSCLC cells and tumor-infiltrating lymphocytes. This study provides evidence that lymphocytic FOXP3 expression may be age related and that tumor FOXP3 expression is correlated with lymph node metastasis.

The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival.

BACKGROUND: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386 C/T and -31 G/C polymorphisms were investigated. METHODS: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR. RESULTS: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the -31 G/C snp may be related to CRC development and improved overall survival. CONCLUSION: Our results support a role of survivin in colorectal carcinogenesis while the -31 G/C snp may constitute a marker of survival.

The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival.

BACKGROUND: survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and -31G/C polymorphisms were investigated. METHODS: quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR. RESULTS: expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the -31G/C snp may be related to CRC development and improved overall survival. CONCLUSION: our results support a role of survivin in colorectal carcinogenesis while the -31G/C snp may constitute a marker of survival.