The Principles of Clinical Cytogenetics - Extra Materials - Springer

Fluorescence In Situ Hybridization 477
Fig. 14. FISH for rearrangement of the SYT locus in a synovial sarcoma. Probes on the telomeric and centromeric
sides of SYT are detected with FITC (green) and Texas Red, respectively. One pair of green–red probe
signals is split apart in each cell as a result of the rearrangement of the SYT gene.
genes that play a role in the pathophysiology of solid tumors are identified, it is likely that clinical
FISH applications for these neoplasms will be developed and marketed.
HER2 and Breast Cancer
Amplification of the HER2 (Her-2/neu) gene and/or overexpression of the protein product, which
has been demonstrated in approximately 25% of breast cancers, has been associated with poor
prognosis, increased risk for recurrence, and shortened survival in breast cancer patients (68,69).
HER2 assessment is useful for prognosis, chemotherapy responsiveness, and selection for targeted
monoclonal antibody therapy (Herceptin ® ) (69). FISH is the most sensitive and specific Food and
Drug Administration (FDA)-approved methodology for HER2 detection (70). FISH with a probe
for the HER2 gene (17q11.2) and, usually, an α-satellite probe for the centromere of chromosome
17 (in a second color) are hybridized to 4-micron sections of paraffin-embedded tumor samples
that have been identified by a pathologist. The invasive component of the cancer is scored for the
number of signals, and a HER2 : 17 centomere ratio is calculated. A ratio of 2.0 indicates HER2
gene amplification (see Fig. 15). These results are used in conjunction with clinical findings to
guide treatment options for the patients.
Bladder Cancer Screening
Bladder cancer is a relatively common cancer that has a greater than 70% chance of tumor recurrence
(71). A multi-target FISH assay has been developed for diagnosis and for monitoring recurrence
of bladder cancer in conjunction with cystoscopy (UroVysion, Vysis, Downers Grove, IL). A
panel of probes, consisting of α-satellite probes for chromosomes 3, 7, and 17 and a locus-specific
probe for 9p21 (see Fig. 16), are used to detect chromosomal aberrations that are commonly associated
with bladder cancer (72). The probes are hybridized to cells from voided urine or bladder washing
samples and are used to detect aneuploidy for chromosomes 3, 7, and 17 and homozygous loss of
the 9p21 locus. The overall specificity is estimated to be greater than 94% in patients without bladder
cancer and the sensitivity is approximately 71%, which is considerably better than the standard cytology
testing that has an estimated 40% overall sensitivity. The FISH methodology has been shown to
be particularly useful for the detection of transitional cell carcinoma in cytologically equivocal and
negative urine samples, often providing the earliest measure of bladder cancer recurrence (anticipatory
positives) (73).