Numeric aberrations of HER-2 and chromosome 17 detected by fluorescence in situ hybridization in urine-exfoliated cells from patients with urothelial carcinoma.
OBJECTIVE
To elucidate the clinical significance of the HER-2 gene alterations in urine-exfoliated cells detected by fluorescence in situ hybridization (FISH) in patients with urothelial transitional cell carcinoma.


METHODS
The relative increase of HER-2 (RI-HER2) and gain of chromosome 17 (G-17) in urine-exfoliated cells were examined using DNA probes for HER-2 and the chromosome 17 centromere in 103 patients. In addition, FISH analysis was performed using corresponding paraffin-embedded tissue sections from 45 cases to compare the results obtained using urine-exfoliated cells and those obtained using paraffin-embedded tissue.


RESULTS
RI-HER2 and G-17 was found in 23 (22.3%) and 46 (44.6%) of 103 patients, respectively. RI-HER2 was significantly more frequent in tumors with two or more recurrences (40.7% versus 15.8%, P = 0.010) and in those with carcinoma in situ (CIS) (35.4% versus 15.9%, P = 0.029). G-17 was more frequent in high-grade tumors (69.1% versus 16.7%, P = 0.032), invasive tumors (63.6% versus 14.3%, P < 0.001), and in patients with CIS (77.1% versus 29.0%, P < 0.001). The positive rate for FISH (presence of RI-HER2 and/or presence of G-17) tended to be more frequent in FISH than in cytology. A comparison of the analyses using urine-exfoliated cells and paraffin-embedded tissue showed identical results in 36 (80.0%) of 45 cases.


CONCLUSIONS
Numeric alterations of the chromosome 17 centromere in urine-exfoliated cells detected by FISH may reflect the malignant potential of urothelial carcinoma. In addition, a relative increase in HER-2 was associated with the number of recurrences and the presence of CIS.
Inoue
Takamitsu
T
Department of Urology, Akita University School of Medicine, Akita City, Japan.
Sato
Kazunari
K
Tsuchiya
Norihiko
N
Matsuura
Shinobu
S
Iinuma
Masahiro
M
Habuchi
Tomonori
T
Kato
Tetsuro
T
D000368:Aged; D000782:Aneuploidy; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology / Q000652:urine; D002503:Centromere / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016612:Paraffin Embedding; D014556:Urine / Q000166:cytology*; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000652:urine