Adult ; Aged ; Female ; Fibroblast Growth Factor 1 ; genetics ; Fibroblast Growth Factor 2 ; genetics ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; analysis ; Receptor Protein-Tyrosine Kinases ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptors, Fibroblast Growth Factor ; genetics

OBJECTIVETo study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer.

METHODSThe expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared.

RESULTSThe positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups.

CONCLUSIONBreast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.

Adult ; Age Factors ; Aged ; Breast Neoplasms ; chemistry ; pathology ; Female ; Fibroblast Growth Factor 2 ; analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Postmenopause ; Receptor, Fibroblast Growth Factor, Type 1 ; analysis ; Receptors, Estrogen ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

Apert syndrome is an uncommon congenital disorder characterized by malformation of the skull in association with symmetrical syndactyly of both hands and feet. This syndrome is autosornal dominant. The original description was presented by Apert in 1906. Since then more than 200 cases have been reported in the world. Recently, we experienced a case of newhorn male infant with congenital anomalies of the skull and extremities. Molecular biologically, he was found to have Ser252Try mutation in the FGFR2 exonIIIa. A brief review of literature was made.
Acrocephalosyndactylia ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Extremities ; Fibroblast Growth Factors* ; Fibroblasts* ; Foot ; Hand ; Humans ; Infant ; Male ; Receptor, Fibroblast Growth Factor, Type 2* ; Receptors, Fibroblast Growth Factor* ; Skull ; Syndactyly

PURPOSE: The fibroblast growth factor receptor 3 (FGFR3) gene is known to be frequently mutated in noninvasive urothelial carcinomas of the bladder. In this study, we investigated the expression of FGFR3, Ki-67, and p53 in bladder cancers and the effects of expression on tumor recurrence. MATERIALS AND METHODS: Fifty-five cases of primary bladder cancer were examined by immunohistochemistry. The relationship of these markers with various clinicopathological factors, including recurrence, was assessed. RESULTS: Positivity for cytoplasmic FGFR3 (FGFR3-c) was associated with a lower cancer grade (p=0.022) and stage (p=0.011). Recurrence was more frequent in patients with a higher stage, negative FGFR3-c, and high Ki-67 expression. According to univariate analysis, predictors of recurrence-free survival included the following: age, stage, FGFR-c, Ki-67, and p53. However, none of these was independent from the other parameters in multivariate studies. CONCLUSIONS: The immunohistochemical expression of FGFR3 is not only one of the characteristic features of lower-grade and lower-stage urothelial carcinoma but also a possible marker in predicting disease recurrence.
Carcinoma, Transitional Cell ; Cytoplasm ; Fibroblast Growth Factors ; Fibroblasts ; Genes, p53 ; Humans ; Immunohistochemistry ; Receptor, Fibroblast Growth Factor, Type 3 ; Receptors, Fibroblast Growth Factor ; Recurrence ; Urinary Bladder ; Urinary Bladder Neoplasms

The C749G(Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. In this study, the blood of 9 Korean children with non-syndromic craniosynostosis were collected and mutation analyses were performed to screen whether this Pro250Arg mutation is also prevalent in Korean population. The genomic DNA samples were analysed by PCR amplification to amplify exon 7 and flanking intron sequence of FGFR3 (341 bp). Restriction digests were analysed by gel electrophoresis. There were no heterozygous for Pro250Arg mutation. No mutations in restriction enzyme digestion were confirmed by direct DNA sequencing. In this study, only 9 patients with simple craniosynostosis were subjected to mutation detection. Therefore, it is necessary to study a large number of patients in order to understand the proportion of non-syndromic craniosynostosis attributalbe to FGFR3 mutation. The epidemiologic study of this disease should be also combined in addition.
Child ; Craniosynostoses* ; Digestion ; DNA ; Electrophoresis ; Exons ; Fibroblast Growth Factors* ; Fibroblasts* ; Humans ; Introns ; Polymerase Chain Reaction ; Receptor, Fibroblast Growth Factor, Type 3* ; Receptors, Fibroblast Growth Factor* ; Sequence Analysis, DNA

The C749G(Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. In this study, the blood of 9 Korean children with non-syndromic craniosynostosis were collected and mutation analyses were performed to screen whether this Pro250Arg mutation is also prevalent in Korean population. The genomic DNA samples were analysed by PCR amplification to amplify exon 7 and flanking intron sequence of FGFR3 (341 bp). Restriction digests were analysed by gel electrophoresis. There were no heterozygous for Pro250Arg mutation. No mutations in restriction enzyme digestion were confirmed by direct DNA sequencing. In this study, only 9 patients with simple craniosynostosis were subjected to mutation detection. Therefore, it is necessary to study a large number of patients in order to understand the proportion of non-syndromic craniosynostosis attributalbe to FGFR3 mutation. The epidemiologic study of this disease should be also combined in addition.
Child ; Craniosynostoses* ; Digestion ; DNA ; Electrophoresis ; Exons ; Fibroblast Growth Factors* ; Fibroblasts* ; Humans ; Introns ; Polymerase Chain Reaction ; Receptor, Fibroblast Growth Factor, Type 3* ; Receptors, Fibroblast Growth Factor* ; Sequence Analysis, DNA

BACKGROUND: Achondroplasia is the most common form of dwarfism. The achondroplasia class consists of achondroplasia, thanatophoric dysplasia and hypochondroplasia. Clinical symptoms are variable, but the common gene, fibroblast growth factor receptor 3 (FGFR3), could account for these variable conditions. We tried to isolate the molecular defects in Korean patients with achondroplasia and hypochondroplasia. METHODS: The sites frequently mutated (G380R and N540K) of the FGFR3 gene of seventeen Korean patients with skeletal dysplasia (16 cases of achondroplasia and one of hypochondroplasia) were analyzed by PCR-RFLP and confirmed by direct sequencing. RESULTS: Missense mutations, which cause G380R of the FGFR3, were present in 15/16 (93.7%) achondroplasia patients. Among these, G to A transition was found in 14 of the 15 (93.3%) patients, and a G to C transversion in a single (6.6%) patient. One case did not show any mutation of the FGFR3 gene reported in achondroplasia, including G375C. A patient with suspected hypochondroplasia exhibited the common C to G transversion mutation, resulting in N540K. CONCLUSIONS: The mutations at codons 380 and 540 of the FGFR3 gene were also found to be common causative mutations of achondroplasia and hypochondroplasia, respectively, in Koreans. These mutations could be used as the target of molecular diagnosis. Based on this simple molecular study, genetic counseling for skeletal dysplasia and prenatal diagnosis will be possible.
Achondroplasia* ; Codon ; Diagnosis ; Dwarfism ; Fibroblast Growth Factors* ; Fibroblasts* ; Genetic Counseling ; Humans ; Mutation, Missense ; Prenatal Diagnosis ; Receptor, Fibroblast Growth Factor, Type 3* ; Receptors, Fibroblast Growth Factor* ; Thanatophoric Dysplasia

Craniosysostosis syndrome is caused by premature fusion of bones of skull and face during fetal development. It is related to Fibroblast growth factor receptor gene and most common craniosynostosis syndromes are Apert, Pfeiffer and Crouzon. Apert syndrome is one of the severe type of craniosynostosis syndromes which shows mutations in the Fibroblast growth factor receptor 2 (FGFR2) gene. Pfeiffer syndrome is also related with FGFR 1 or 2 gene mutation. We experienced two patients with craniosynostosis syndromes, Apert syndrome and Pfeiffer syndrome. The first baby was a in-born female baby presented with syndactly of the hands and feet and facial dysmorphism including shallow orbit with deep crease above eye brow. Apert syndrome was confirmed by the presence of a mutation in FGFR2. The second patient visited our developmental delay clinic due to developmental delay at seven month old age. He showed facial dysmorphism including cloverleaf-shaped skull, micrognathia, low set ears, low nasal bridge and high-arched palate, but there were no syndactly or limb anomalies. He was suspected of Pfeiffer syndrome, however his FGFR2 gene study was normal. These patients need multidisciplinary team management and regular follow up for visual, auditory, and cognitive development functions Pediatricians have important role on recognizing the patients with facial dysmorphism, planning to evaluate accompanying anomalies and making appropriate decisions about the timing of surgical management to minimize growth and cognitive impairments.
Acrocephalosyndactylia ; Craniosynostoses ; Ear ; Extremities ; Female ; Fetal Development ; Follow-Up Studies ; Foot ; Hand ; Humans ; Orbit ; Palate ; Receptor, Fibroblast Growth Factor, Type 2 ; Receptors, Fibroblast Growth Factor ; Skull

OBJECTIVETo detect the IgH-MMSET fusion gene resulted from t (4;14) translocation in multiple myeloma and illuminate its significance.

METHODSIgH-MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR) assay followed by nested PCR to increase the sensitivity. The purified PCR products were cloned into pGEM-T vector and then sequenced using M13 forward primers. The fragment sequences were compared with that in GenBank to find matched sequences.

RESULTSOnly a 438 base pair long fragment was obtained after RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within the C micro region of IgH gene on chromosome 14 and intron 3 of MMSET gene on chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients through nested PCR assay. The amplified fragments of the 3 patients were 237 base pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on chromosome 4 were identical to that of NCI-H929 cell.

CONCLUSIONSThe formation of IgH-MMSET fusion gene is resulted from t (4;14) translocation in MM. The incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor prognosis.

Adult ; Aged ; Base Sequence ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 4 ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Multiple Myeloma ; genetics ; Oncogene Proteins, Fusion ; genetics ; Protein-Tyrosine Kinases ; Receptor, Fibroblast Growth Factor, Type 3 ; Receptors, Fibroblast Growth Factor ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic

PURPOSE: Genetic variation in fibroblast growth factor receptor 2 (FGFR2) is a newly described risk factor for breast cancer. This study aimed to evaluate the association of four single nucleotide polymorphisms (SNPs) in FGFR2 with breast cancer in Han Chinese women. METHODS: Two hundred three women with breast cancer and 200 breast cancer-free age-matched controls were selected. Four SNPs (rs2981579, rs1219648, rs2420946, and rs2981582) and their haplotypes were analyzed to test for their association with breast cancer susceptibility. The presence of the four FGFR2 SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A statistically significant difference was observed in the frequency of rs2981582 in the FGFR2 gene (p<0.05) between case and control groups. In subjects stratified by menopausal status, rs2981582 TT, rs2420946 AA, and rs1219648 CC were significantly associated with the risk of breast cancer in postmenopausal subjects, but no significant associations between these four SNPs and the risk of breast cancer were identified in premenopausal subjects. Further, there was no significant association between hormone receptor status (estrogen receptor and progesterone receptor) and breast cancer risk. Six common (> 3%) haplotypes were identified. Three of these haplotypes, CGTC (odds ratio [OR], 0.613; 95% confidence interval [CI], 0.457-0.82; p=0.001), TGTC (OR, 6.561; 95% CI, 2.064-20.854; p<0.001), and CATC (OR, 12.645; 95% CI, 1.742-91.799; p=0.001) were significantly associated with breast cancer risk. CONCLUSION: Our findings indicated that the SNP rs2981582 and haplotypes CGTC, TGTC, and CATC in FGFR2 may be associated with an increased risk of breast cancer in Han Chinese women.
Asian Continental Ancestry Group* ; Breast ; Breast Neoplasms ; Case-Control Studies* ; Female ; Fibroblast Growth Factors* ; Fibroblasts* ; Genetic Variation ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Progesterone ; Receptor, Fibroblast Growth Factor, Type 2* ; Receptors, Fibroblast Growth Factor* ; Risk Factors