Edit Nádasi

Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer

To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER‐2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.

Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion

The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.

Oncogene and tumor suppressor gene expression changes in the peripheral blood leukocytes of patients with colorectal cancer

Aims and background The mortality of colorectal cancer continues to stagnate despite the development of new therapeutic approaches. Therefore, identifying high-risk population groups could contribute to the prevention of a considerable part of deaths caused by colorectal tumors. Methods Fifty patients with colon cancer and 50 patients with other, nonmalignant diseases were selected for the study. Expression of the c-myc, Ha-ras and p53 genes was determined in the peripheral leukocytes of the participants. Results Marked elevations of the expression of all three investigated genes were seen in the colon cancer patients when compared to the controls. Conclusions Our investigations showed that increases in the expression of c-myc, Ha-ras and p53 genes can be demonstrated in the peripheral leukocytes of colon cancer patients. By applying our method to clinical investigations, individuals with a high risk of having developed colon cancer may be identified and early diagnosis may be established.