03/19/08

 

BY AMY ADAMS

	Courtesy of Mauna Kea Technologies
	The Cellvizio GI uses a miniaturized microscope to peer inside the colon and look for telltale spots of cancerous cells.

Doctors may one day be able to detect early stages of colon cancer without a biopsy, using a technique from researchers at the School of Medicine.

The imaging technology is one of many new ways of detecting cancers in the body in real time, said Christopher Contag, PhD, associate professor of pediatrics and of microbiology and immunology, who led the study. Contag hopes it might be one of the first used routinely for early detection of cancer.

"Detecting colon cancers is just the first step," said Contag. He predicted similar techniques will be able to find a wide range of cancers, monitor treatment and deliver chemotherapy directly to cancer cells in the colon, stomach, mouth and skin. The study was published online March 16 in Nature Medicine.

Colon cancer is the third most common cancer with about 150,000 people diagnosed each year. Although colonoscopy isn't perfect, it's currently the best way of finding colon cancers when they are still at the most treatable stage.

If doctors find suspicious growths during a routine colonoscopy, they take a sample, called a biopsy, and send it to a pathology lab to screen for cancer. That step takes time and not all people have ready access to a nearby pathologist. What's more, doctors biopsy only cancers that form easily visible growths, or polyps. Early stage cancers that are flat aren't detected.

The trick to detecting cancer without biopsy is to find a way to see cancerous cells while still in the body. That's what Contag and his group succeeded in doing.

The group found a short protein that stuck to colon cells in the early stages of cancer. Before screening a person, they sprayed the short protein attached to a fluorescent beacon into the colon. The protein glommed onto any cancerous cells and created an easily visible fluorescent patch. They then used a miniaturized microscope called Cellvizio GI, developed by Paris-based Mauna Kea Technologies and loaned to Contag, to peer inside the colon and look for those telltale spots.

The researchers not only saw fluorescent patches, they made out individual cancerous cells. That fine resolution allowed doctors to pick up the earliest cancers. Contag said it could also be a useful research tool for studying the small number of cancer stem cells that are thought to establish the eventual tumor.

In the initial trial of 15 patients, the technique detected 82 percent of the polyps that were considered cancerous by a pathologist. Contag said the next step is to work with some of the additional small proteins they've found that also attach to cancerous cells. He thinks that a combination of those proteins will make the technique highly accurate.

Once the screen is ready for widespread use, Contag said it could bring accurate cancer detection to people in remote locations who don't have access to pathology labs. "A doctor could send a video in real time via the Internet to someone trained to analyze the living cell images," Contag said. This could help people begin the appropriate therapy when the cancer is still at an early stage.

	Christopher Contag

Contag thinks this technique, developed in part through the cancer imaging program at the Stanford Cancer Center, could be adapted to detect cancers in the mouth, esophagus and stomach. Also, real-time screening could be used to assess whether a chemotherapy regimen is working. Contag said that if a tumor responds to a given chemotherapy, changes in the cells might be visible immediately. That response could allow doctors to switch patients to a new, more effective treatment if the first one results in no improvement. Currently people go through several rounds of chemotherapy before the first screen to find out if the treatment helps, a delay that keeps people from moving quickly to an effective treatment.

The work was funded by the National Institutes of Health, the Doris Duke Charitable Foundation, the School of Medicine Dean's Fellowship and the John and Cynthia Fry Gunn Research Fund.

Additional researchers who contributed to the study were postdoctoral scholar Pei-Len Hsiung, PhD; Jonathan Hardy, PhD, research associate; assistant professors of medicine Shai Friedland, MD, and Roy Soetikno, MD; Christine Du, research assistant; Amy Wu, MD, medical student at that time; Peyman Sahbaie, MD, scientist at the Molecular Research Institute in Palo Alto; Anson Lowe, MD, associate professor of medicine, and Thomas Wang, MD, PhD, former clinical instructor of medicine who is now at the University of Michigan.