Technical and analytical advances have facilitated the application of high-throughput analysis to clinical specimens, a process that has been referred to as "molecular profiling." This term, as applied here, may refer to identifying various "markers," including genomic, proteomic, and epigenomic expression patterns, or a combination thereof. Technologic advances have led to the ability to measure thousands of genes by a variety of validated methods,[1] and analytical models have been developed that facilitate analysis of the voluminous amount of data that are generated.[2]
This technology has enabled "discovery-based research" to be conducted, in which large volumes of data are generated from clinical specimens and analyzed without a specific hypothesis, in contrast to the traditional scientific paradigm of "hypothesis-based research," in which a limited number of genes/proteins are investigated based upon a specific hypothesis and rationale.[3] Discovery-based and hypothesis-based research are not mutually exclusive, however—profiling may also be used to test specific hypotheses that are based upon sound scientific rationale.
Promise and Pitfalls of Gene-Expression Profiling
Evaluation of the genomic expression patterns of clinical specimens that are linked to classical clinicopathologic, treatment, and outcome information has led to the development of several multigene markers that are nicely described in this review by Drs. Henry and Hayes, and which have also been reviewed elsewhere.[4] The authors outline the potential promise and pitfalls of the clinical application of gene-expression profiling for localized-stage breast cancer, with emphasis on its potential for predicting chemotherapy benefit in patients with hormone receptor–positive disease.
The application of genomic profiling may lead to the following scenarios in patients with hormone receptor– positive disease who clearly benefit from hormonal therapy:
• "treatment sparing" in those with a favorable genomic profile who may be adequately treated with hormonal therapy but would have been offered chemotherapy because of unfavorable clinicopathologic features;
• "treatment selection" in those with an unfavorable genomic profile who may be offered chemotherapy in addition to hormonal therapy, but would have been offered hormonal therapy alone based upon favorable clinicopathologic features;
• "treatment direction" in those for whom the genomic profile (whether favorable or unfavorable) provides a clear treatment path despite equipoise about the most appropriate therapy recommendation based upon clinicopathologic features; and
A 48-year-old female presents with complaints of irregular vaginal bleeding and postcoital bleeding. Images from a PET/CT and pelvis MRI reveal characteristic findings. What is your diagnosis?
