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.

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.

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.

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.

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.