Novel RET mutations in macedonian patients with medullary thyroid carcinoma: genotype-phenotype correlations.

Medullary thyroid carcinomas (MTCs) are rare neoplasms comprising 2-10% of all thyroid malignnancies. More than 75% are sporadic tumors and the remainder is familial and MEN2 related. Both sporadic and syndromic MTCs frequently show mutations in the RET proto-oncogene. It has been noted that some MTC cases present an indolent, and some an aggressive clinical course. Ki-67 expression is generally low, with documented exceptions, whereas high expression of Bcl-2 has been reported in majority of the cases. Some studies have shown that Ki-67 and Bcl-2 expressions have prognostic value, as well as RET mutational status. We analyzed 20 unrelated MTC cases for Ki-67, Bcl-2 expression and RET mutations and tested their intercorrelations, correlations to the morphologic features and stage of the tumors, as well as their influence on survival. In 13 of the 20 analyzed cases we found 23 sequence changes distributed in exons 8, 10-13 and 16. There were 11 different missense mutations, single nucleotide deletion with frameshift, and 8 different synonymous mutations. Only 4 of the sequence changes have been previously published. Twelve patients (60%) had tumors expressing one or more missense mutations or single nucleotide deletion and 7 of them (35%) had at least one damaging or possibly damaging RET mutation. Most of the tumors had low Ki-67 expression (mean 6.48% of cells) and high Bcl-2 expression (mean 68.3%). Significantly better survival was observed in cases with low Ki-67 (< 6.5%; p < 0.05), high Bcl-2 expression (> 68.3%; p < 0.01) and younger age at diagnosis (< 51 years; p < 0.05).

N-terminal-proB natriuretic peptide in patients with stable coronary artery disease evaluated for ischemia with myocardial perfusion imaging.

BACKGROUND: Natriuretic peptides have emerged in the last years as useful diagnostic and prognostic biomarkers in patients with stable CAD. Myocardial ischemia per se might increase NT-proBNP levels. OBJECTIVES: The aim of the present study was to determine whether NT-proBNP levels in patients with stable CAD and preserved left ventricular function are elevated and second, to compare NT-proBNP in patients with verified ischemia on myocardial perfusion imaging (MPI) to non-ischemic subjects with known CAD. METHODS: 117 patients were prospectively included, divided in two groups: group A (26 patients)--with normal MPI and without known CAD and group B (91 patients)--with abnormal MPI or known CAD. Patients from group B were further divided according to the presence of ischemia on MPI in non-ischemic (29 pts) and ischemic (62 pts) subgroup. RESULTS: Levels of NT-proBNP in group B were significantly higher compared to group A (median 53 vs 21 pg/ ml, p = 0.012). End diastolic and end systolic volumes were higher, and ejection fraction after stress and at rest was lower in group B (63% vs 71%, p = 0.0004 and 69% vs 75%, p = 0.008). No significant difference in NT-pro BNP levels (median 48 vs 62 pg/ml, p = 0.5) and functional parameters between the ischemic and nonischemic subjects was found. CONCLUSION: Our data show that patients with stable coronary artery disease and preserved left ventricular function have elevated levels of NT-proBNP. We could not demonstrate that the presence of myocardial ischemia per se was an additional factor leading to increase of the natriuretic propeptide (Tab. 4, Ref. 12).