Fibroid tumors affecting many American women lack a key protein helps hold tissues together

Fibroid tumors — the sometimes painful uterine growths affecting many American women — lack a key protein that plays a role in holding tissues together, according to a study by researchers from the Uniformed Services University of the Health Sciences (USUHS) and the National Institute of Child Health and Human Development of the National Institutes of Health.

"This finding is a major step in understanding the nature of fibroids and may prove useful in efforts to devise more effective treatments for them," said Duane Alexander, M.D., Director of the NICHD.

The study has been published on line at http://www3.interscience.wiley.com/cgi-bin/jhome/38250 and will appear in the July 2004 issue of Genes, Chromosomes and Cancer.

Specifically, the researchers discovered that fibroids have low levels of the protein dermatopontin. The protein is a key component of the extracellular matrix — the elastic meshwork of collagen and other proteins that keeps cells in place. Moreover, the researchers learned that another type of growth, keloids, also lack dermatopontin. Keloids are an overgrowth of thick scar tissue that can form on the skin after a cut or other wound heals. Both keloids and fibroids disproportionately affect African Americans.

Fibroids, also known as leiomyomas, are noncancerous growths that develop in the myoemetrium, the smooth muscle tissue of the uterus, explained William Catherino, M.D., Ph.D, of NICHD's Pediatric and Reproductive Endocrinology Branch.

Women with fibroids may experience painful menstrual periods, pain during sexual intercourse, infertility, urinary and fecal incontinence, and bowel obstruction, Dr. Catherino said. They are also more likely to go into labor prematurely and to experience a miscarriage.

Dr. Catherino added that it's difficult to know exactly how many women in the United States have fibroids, because in many cases fibroids do not cause symptoms, he said. Some studies using ultrasound have indicated that 70 to 80 percent of women may have the growths but do not experience any problems from them. About one out of every 2 to 4 women will have symptoms from fibroids at some point during their reproductive years. For women who experience severe symptoms, treatment often involves surgery. In one form of surgery, myomectomy, the fibroids are removed from the wall of the uterus. In many cases, the fibroids return after surgery or their removal results in the formation of painful scar tissue.

In other cases, the number of fibroids is so great that hysterectomy (removal of the uterus) must be performed. According to the Centers for Disease Control and Prevention, fibroids are the single greatest reason for hysterectomy, accounting for 27 percent of the 650,000-675,000 hysterectomies performed in the United States each year.

In the study, researchers used a technique known as microarray analysis to determine the activity levels of genes in fibroid tumors. They examined both fibroid tissue and normal uterine tissue from 11 women who underwent hysterectomy as a treatment for fibroid symptoms. They also examined samples of keloid tissue provided by another lab.

The researchers found that the fibroid tissue had lower levels of dermatopontin than did the normal uterine tissue. They also discovered that keloid tissue had low levels of dermatopontin. Both the fibroid tissue and the keloid tissue contained disorganized, unstructured strands of collagen, Dr. Catherino said. In normal tissues, collagen forms discrete strands.

Dr. Catherino and his colleagues suspect that fibroid tumors have a genetic basis. Moreover, the same genetic factors that may predispose African American women to develop fibroids may also play a role in African Americans' predisposition toward keloids. He and his coauthors wrote that African American women are 3.3 times more likely to develop fibroids than are Caucasian American women and 3 times more likely to develop keloids than are Caucasian American women.

Other evidence also points to a genetic basis for fibroids. Women whose mothers, sisters or daughters have fibroids are more likely to have fibroids themselves. Similarly, women with the genetic disorders Alport Syndrome and Reed Syndrome are more likely than other women to have fibroids.

Dr. Catherino hypothesizes that dermatopontin plays a role in preventing the muscle cells of the uterus — known as myometrial cells — from developing into another type of cell. Dermatopontin appears to react with the integrin receptor on myometrial cells. Like a key fits into a lock, molecules interact with cell receptors to bring about changes in the cell. The integrin receptor and molecule appear to be important for influencing the type of cell that a cell will become.

Dr. Catherino suspects that a failure of dermatopontin to interact with the integrin receptor results in the cell losing its function as a myometrial cell and becoming more like a fibroblast — a type of skin cell that produces collagen. In fact, the individual cells in fibroids are referred to as myofibroblasts, because they have characteristics of both myometrial cells and fibroblasts.

Additional information about fibroids is available from the NICHD publication, Uterine Fibroids. This publication, along with other NICHD publications, is available on the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; e-mail [email protected].