Healthy tissue aids cancer research in Indianapolis


INDIANAPOLIS (AP) -- Theresa Mathieson slowly opened the cold storage tank and removed a stack of glass slides.

Inside the tank were hundreds of tissue samples donated by women and frozen in liquid nitrogen.

Somewhere in that stack, Mathieson and others at the Indiana University Simon Cancer Center hope to find the cure for breast cancer.

The Susan G. Komen for the Cure Tissue Bank is the only U.S. facility to collect, catalog and analyze healthy breast tissue for research. By comparing these samples to those from women with breast cancer, scientists hope to find out exactly what goes wrong in the cells to cause tumors.

"You can finally have an idea of exactly what is going wrong in a cell," Dr. Susan Clare said. "Before, we were kind of guessing. But now we have enough normals that we can figure out what the range of normal is. If we find something outside that range, we know it's somehow related to cancer."

Clare is one of the tissue bank's main investigators, helping lead the research that comes from the donated tissue samples. Over the course of four years, they have helped provide base samples for cancer researchers all over the world to analyze against cancer cells.

The bank started in 2005 with a mass blood donation at the annual Susan G. Komen Race for the Cure. More than 1,200 samples from healthy women were brought in and stored in the cancer center's bank of freezers.

Researchers wanted to expand the collection to tissue taken directly from the breast. But hospital administrators required convincing before they allowed taking samples from healthy women.

Donation requires women to have a small slice of tissue cut from within their bodies. Though the procedure was simple and took only about 30 minutes, administrators were concerned that women wouldn't volunteer to go through that.

But the response has been overwhelming. So far, more than 1,500 women have donated to the bank.

The samples came from women of all races, body types and ages. But all of them have one thing in common -- they've never exhibited signs of breast cancer.

Since opening in 2007, the bank has scheduled special donation days to bring in as many women as possible to donate.

Every donor must fill out a thorough health evaluation beforehand. The questionnaires ask about each woman's health history, menstrual cycle, how many children they have and their diet.

"The sample becomes exponentially more valuable as we know more about the lady," Clare said. "That way, we can deduce what might be causing potential differences between cancerous and healthy tissue."

Women then are taken to a clinic room, where their breast is sterilized, numbed with local anesthesia and slightly nicked with a scalpel.

Using a needle, the surgeon removes a small specimen from within the breast.

The tissue is placed on dry ice immediately and taken to Mathieson, who then adds it to the bank's freezers. Tissue stored in the bank's liquid-nitrogen tanks is kept around minus 292 degrees.

Flash freezing it and preventing it from thawing keeps the tissue from reacting to the outside conditions and changing in any way, Clare said.

"We want these samples to be as close to what they were in the breast as possible," she said. "We don't want to introduce anything abnormal."

Traci Runge, 43, a Carmel resident, volunteered to donate at one of the bank's first collection events in 2007. She was motivated to give after watching the mother of one of her cheerleading students struggle with the disease. Runge and this mom both had young children.

"I was very bothered. Here she was with an infant, and she was sick. And here I was with an infant, and I was fine," Runge said.

She went through the blood draw and the needle biopsy. The procedure stung but wasn't painful for long, Runge said.

"Up to this point, they've done all kinds of research on the tumors themselves but never really looked at the normal tissue to find out what changes are made," she said. "If I can help save just one life, then it's worth it."

From a research standpoint, Runge might be the most important donor of all, Clare said. In early 2010, she was diagnosed with breast cancer herself. She donated the cancerous tissue, as well as additional healthy tissue from her other breast.

Along with the first healthy sample taken in 2007, Runge presents researchers a preserved before-and-after picture of the molecular changes breast cancer can cause.

"The possibilities of what they can learn is amazing," Runge said. "If I can do this as a way to save someone's life, especially my three little girls, it's what I had to do."

Protecting and preserving every donation that is made falls to Mathieson, the specimen manager for the bank. She is in charge of monitoring the conditions of all the samples, preparing them for shipping and logging all of the information in the database.

Most of the tissue is sent to researchers around the world, so it's vital to record everything from the time of day it was sampled to the temperature at which it was frozen.

"When a researcher requests samples, they know exactly that what they're getting has been collected in a very standardized way," she said. "We know the history, the circumstances in which it was collected, and that can affect the research."

The tissue bank receives about 15 requests for tissue each year. Research teams specify what they're looking for, depending on the types of women or the circumstances in which the tissue was collected.

Researchers can access a database of the bank's samples online and determine if the Indiana University Simon Cancer Center has any tissue that meet their requirements.

After submitting a proposal, each research project is debated by a three-person panel on the validity of the work.

"These are so precious. They're gifts of science, so it's important that we're great stewards with this tissue," Clare said.

So far, the bank has provided samples for close to 60 research projects. Scientists at Harvard University, the National Institutes of Health and the Queensland Institute of Medical Research in Australia have used the bank's tissue to study on the molecular level.

The Mayo Clinic is on the verge of publishing results that compare the typical cells in benign tumors to healthy tissue.

IU Simon Cancer Center researchers have compared healthy samples against those from women with triple negative breast cancer. Triple negative breast cancer doesn't exhibit the three main indicators found in cancer genes.

Doctors have been clueless about what sets these women apart from others who have breast cancer.

They found hundreds of genes that differed between normal tissue and the triple negative tissue. One by one, scientists can examine the genes and possibly determine a new indicator for these cancers, Clare said.

None of the work has been published yet, so Clare was hesitant to release any information about the projects. But she expects the first round of papers to hit medical journals this year.

Clare and the bank's other lead investigator, Dr. Anna Maria Storniola, also are making records of the DNA of each woman who has donated to the tissue bank to see how the genetics of a healthy woman differ from a woman with breast cancer.

A tiny section of every sample is taken to the tissue bank's laboratory for examination. Researchers stain the breast tissue purple, which lets them identify the milk duct cells underneath a high-powered microscope.

A computerized laser cuts the duct cells out of the sample, dropping each in a test tube and sealing it off.

"Cancer starts in the milk duct, so we want to get it away from everything else," Clare said. "When we have it isolated, we can take it to our sequencing center and identify its individual DNA."

Inside the bank's research lab, Diane Doxey worked the microscope, culling a large bank of duct tissue. By using the computerized laser, Doxey and other researchers can catalog dozens of samples each day.

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