Researchers from The Rockefeller University and Digilab, using a technique called infrared (IR) spectroscopy, have shown that normal-looking cells taken from women with cervical cancer may actually be abnormal. The findings, published in the Dec. 22 issue of the Proceedings of the National Academy of Sciences, may expand the definition of cancer, and lead to improved diagnostic techniques, such as reading of Pap smears.
"These results show that when cervical cancer develops, the normal-looking cells surrounding those that are visibly abnormal have extensive and measurable changes," says co-author Basil Rigas, M.D., an adjunct faculty member at Rockefeller. "Our findings may lead to improved techniques for diagnosing and treating cancer, by shifting the definition of a cancer cell from the current one-which is based on the morphological features of a cell-to one based on chemical changes picked up by infrared spectra."
Doctors usually depend on the Pap test as a method to detect cervical cancer and precancerous lesions known as dysplasia in women. In the Pap test, cells are taken from the cervix and sent to a laboratory, where technicians look at the cells under the microscope. Samples that contain suspicious cells are then evaluated in detail by specialists. The error rate of the Pap test has been reported to be between 10 and 60 percent, in part attributable to its subjective nature.
In the new study, Rigas and his co-author, Menashi A. Cohenford, Ph.D., of the Digilab Division of Bio-Rad, used IR spectroscopy to look at more than 2,000 individual cervical cells from 22 women. Ten of the women were normal, seven had dysplasia and five had cervical cancer. Half the sample was analyzed by IR and the other half by Pap test, confirming the initial diagnosis.
IR spectra reflect the chemical composition of cells. IR spectroscopic analysis of the so-called normal cells taken from women with dysplasia and cervical cancer showed that the cells, though normal-looking under a microscope, actually produced spectra that were distinctly abnormal. The changes in the spectra mirrored the process of cervical cancer, becoming progressively more pronounced as the cervical samples moved from normal to dysplasia to cancer.
The researchers do not know whether changes in the IR spectra reflect the cause of cancer or are simply a result of it. One of the possibilities considered by the authors is that the changes in spectra may reflect the presence of the human papilloma virus, whose role in cervical cancer is well known.
These findings, when confirmed and expanded by larger studies, could simplify the evaluation of Pap tests. "Because normal-looking cells of cancerous specimens constitute the majority of cells, it may be far easier to assess the status of these cells than to look for the few cells that appear abnormal under the microscope," says Rigas.
IR spectral abnormalities have been observed by Rigas and others in several cancers, although such detailed analysis has been performed only on cervical samples. If changes similar to those observed in the normal-looking cells of the cervix occur in other cancers, cancer treatment may be affected by these findings. For example, for cancers that are surgically removed, doctors cut out the cancerous cells, leaving normal tissue behind. Using IR spectroscopy, surgeons could identify cells that appear normal, but are really abnormal. Removing these additional cells would make the excision of the tumor more effective.
Finally, the authors suggest that their findings could enable physicians to prevent cancer in earlier stages.
"We can envision a situation in which the definition of cancer, currently based mostly on the application of morphological criteria to tissue sections, would involve assessment of these cells by IR spectroscopy," says Rigas. "We expect that this approach will reveal earlier forms of cancer, which could direct the study of cancer to as of yet unrecognizable premalignant forms, representing more preventable stages of cancer."
Rockefeller began in 1901 as The Rockefeller Institute for Medical Research, the first U.S. biomedical research center. Rockefeller faculty members have made significant achievements, including the discovery that DNA is the carrier of genetic information and the launching of the scientific field of modern cell biology. The university has ties to 19 Nobel laureates. Thirty-three faculty members are elected members of the U.S. National Academy of Sciences, including the president, Arnold J. Levine, Ph.D.
Journal
Proceedings of the National Academy of Sciences