Sep 29 2004
Two types of thyroid cancer that are closely related and sometimes difficult to distinguish can be readily identified by differences in only a few genes, new research shows.
The study, by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, used microarray analysis to show that papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) differ in the expression of only four or five genes.
Distinguishing between the two cancers is important because the malignancies behave differently and require different treatment. The research should also help scientists better understand the origins of the two diseases. The study is published in the a recent issue of the Journal of Clinical Oncology.
“This finding suggests a potentially very useful diagnostic aid in those rare instances where the pathologist cannot distinguish between FTC and PTC,” says study leader Dr. Charis Eng, the Dorothy E. Klotz Chair of Cancer Research and director of Ohio State's clinical cancer genetics program.
Thyroid cancer represents one percent of all cancers in the United States and is the most common cancer of the endocrine hormone system. Over the last few years, thyroid cancer has risen at an alarming rate, Eng says. An estimated 23,600 new cases of thyroid cancer are expected this year, nearly two-thirds of which will occur in women, and 1,460 Americans are expected to die from the disease. PTC represents about 80 percent of all thyroid cancers, with FTC representing about 10 percent of cases.
Eng and her colleagues have shown that two distinct groups of genes are either over-active or under-active in PTC cells compared with normal thyroid cells. Genes that were inactive or under-active were more typical of FTC cells.
They further found that five genes could distinguish the two tumor types.
The researchers used microarray analysis, which reveals the activity levels of tens of thousands of genes at one time, to compare gene activity in cells from six PTC tumors, nine FTC tumors and 13 samples of normal thyroid tissue.
The PTC cells showed over-expression of genes known as CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6). It also showed no change in two genes, caveolin-1 (CAV-1) or caveolin-2 (CAV-2). FTC cells, on the other hand, showed no expression by CLDN10 and low activity by IGFBP6 and/or by CAV1 and CAV2.
If verified in a larger number of tumors, these genes, in combination with other known genetic changes in thyroid cancer cells, form the basis for a valuable diagnostic tool, says Eng, a recipient of the Doris Duke Distinguished Clinical Scientist Award.
“Our work begins to elucidate the fundamental differences and similarities between these two types of thyroid cancer, which should help in the future to develop new therapies,” Eng says.
Clinical testing for the genetic differences can be done using polymerase chain reaction (PCR) technology, which is far more available and far less costly than microarray analysis.
Other Ohio State researchers involved in the study were first author Micheala A. Aldred, Sandya Liyanarachchi, Natalia S. Pellegata, Sissy Jhiang, Ramana V. Davuluri and Albert de la Chapelle.
Funding from the National Cancer Institute, and a gift from the Brown family, in memory of Welton D. Brown, supported this research.