Spectrum Medical Group’s Pathology Division has expanded the molecular laboratory diagnostic menu to include an important new technology that provides highly specific genetic information in a variety of settings. Referred to as fluorescent in situ hybridization (FISH), the technique allows for rapid analysis and detection of tumor-related genetic alterations that may be related to the specific diagnosis or prognosis of many tumors.

The underlying basis for FISH techniques is that single strands of specific DNA segments (probes) will bond (anneal) tightly with other single strands of DNA to produce the typical double stranded DNA helix. The probes are produced to have a genetic sequence that will be highly specific for genetic sequences in the tumor cells. The probes are labeled with fluorescent markers that provide a strong visual signal that can be detected under a simple light microscope. The “target cells” (tumor cells that presumably harbor an important genetic abnormality to be detected) undergo denaturation of their DNA (DNA double helix separation) allowing the probe to anneal to its target DNA sequence. When viewed under the microscope the location and number of probes (for a mixture of probes) can be visualized. FISH techniques have the added advantage of preserving cellular morphology so that in many instances probe distribution can be compared in normal and neoplastic cell populations.

Although the technology has very broad diagnostic applications, its current usage at Maine Medical Center is limited to a select number of tests that are frequently ordered. The most common is detection of the oncogene HER-2/neu in breast cancer. Overamplification (excessive amounts) of copies of this gene predicts response to a certain biologic therapy and may be prognostic in advanced stage tumors. Another application is in detection of the Philadelphia chromosome that characterizes most cases of chronic myelogenous leukemia. This abnormality results from a genetic translocation between chromosomes 9 and 22 that results in the transfer of the c-abl oncogene to a site adjacent to the breakpoint cluster (bcr) on chromosome 22 that is easily detected by FISH. FISH technology produces a highly accurate result in a much more rapid turn around time than traditional tissue culture cytogenetics. Finally, the current categorization of many soft tissue tumors is aided substantially by the detection of characteristic cytogenetic abnormalities that are rapidly detected by FISH.

Continued expansion of this technology will allow for the rapid incorporation of highly specific genetic information into routine diagnostic pathology reports as the understanding of the molecular basis of disease merges with the traditional light microscopic interpretations.