Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades.

OBJECTIVE: Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece. PATIENTS AND METHODS: Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened. RESULTS: A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%). CONCLUSION: The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group.

High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

OBJECTIVE: Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. DESIGN AND PATIENTS: Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. MEASUREMENTS AND RESULTS: The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. CONCLUSION: In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece.

Diet, blood lipid profile and physical activity patterns in primary school children from a semi-rural area of Greece.

BACKGROUND: Risk factors for heart disease are becoming increasingly prevalent among young populations. The aim of this study was to assess the cardiovascular risk profile of young adolescents living in a semi-rural area of mainland Greece, Volos. MATERIALS AND METHODS: A total of 198 children (106 females and 92 males) aged 11.6 +/- 0.4 years were randomly recruited. RESULTS: Mean body mass index was 20.4 +/- 3.5 kg m(-2), while 30.3% of children were overweight and 6.7% were obese; no differences were observed between boys and girls. Mean plasma cholesterol (4.93 +/- 0.75 mmol L(-1)), low-density lipoprotein-cholesterol (3.29 +/- 0.64 mmol L(-1)) and triglyceride (0.97 +/- 0.31 mmol L(-1)) concentrations were above age-specific recommended values. On the other hand, mean high-density lipoprotein-cholesterol was acceptable for 92.3% of the children. Self-reported daily energy intake (8.37 +/- 3.06 MJ) was adequate for age, but intake of fat was high (42.0 +/- 9.2% of energy) and that of carbohydrate was relatively low (44.5 +/- 10.0% of energy). Saturated fat consumption was elevated (15.6 +/- 4.3% of energy), while polyunsaturated fat intake fell short (4.8 +/- 1.6% of energy). The study participants spent 9.60 +/- 6.44 h week(-1) on moderate to vigorous physical activities, while they devoted 16.60 +/- 8.81 h week(-1) to sedentary activities. Boys spent significantly more time than girls on both physical (P < 0.001) and sedentary (P = 0.001) activities. No major gender differences were observed in anthropometric, dietary and plasma lipid parameters. CONCLUSION: The findings from the present study support the worrisome trends that have been documented in Greek youngsters elsewhere, and predict an unfavourable cardiovascular risk profile for the Greek population in the foreseeable future.

Role of matrix metalloproteinase-9 in progression of mouse skin carcinogenesis.

Invasion of malignant tumor cells is required for the formation of metastatic colonies. Uncontrolled expression of matrix metalloproteinase (MMP)-2 and MMP-9 is a critical part of the invasive potential of tumor cells and is affected by the balance between the enzymes and the inhibitors secreted by the cell. Here we analyzed the expression and activity of the two gelatinases (MMP-2 and MMP-9) as well as the expression levels of the tissue inhibitor of metalloproteinase (TIMP2)-, in different stages of carcinogenesis using mouse skin cell lines derived from tumors induced by chemical mutagens. Our results suggested that the expression of MMP-9 was implicated in the progression to spindle cell carcinomas in mouse keratinocytes. MMP-2 levels remained steady in all cell lines, whereas levels of TIMP-2 were increased in normal and spindle cells. The AP-1 DNA binding and transcriptional activity on the MMP-9 promoter were increased in the malignant cell lines, indicating the requirement of this binding site for its activation. The results of this study clearly suggested the important role of MMP-9, but not of MMP-2, in the metastatic properties of mouse keratinocytes.

Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer.

BACKGROUND: The levels of matrix metalloproteinases MMP-2 and MMP-9 (type IV collagenases), which degrade the extracellular matrix of the basement membrane, were evaluated as prognostic indicators of metastasis in urothelial carcinoma. MATERIALS AND METHODS: Quantitative gel zymography and immunohistochemistry were used and compared with clinical data at the follow-up period of 36 months. RESULTS: Zymographical analysis of the levels of MMP-9 and active MMP-2 showed a statistically significant increase with tumor grade and invasiveness. This correlation was confirmed by immunohistochemical analysis of MMP-9 expression. However, the correlation between the levels of both gelatinases with recurrence in superficial tumours or progression in invasive tumours was not statistically significant. CONCLUSION: MMPs may have an important role in the invasion mechanism of urothelial cancer and could be useful prognostic markers for patients with bladder carcinoma. The relationship between MMP-2 and MMP-9 expression and the metastatic potential of bladder carcinoma needs further evaluation in subsequent clinical studies.