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Determining whether a mole is a potentially life-threatening melanoma is tricky business, leading to both under- and overdiagnosis. Now, researchers at Weill Cornell Medical College have designed, developed and studied a new diagnostic staining test they say can provide a novel measure of whether a mole is clearly cancerous or benign with the potential for expanded use across all cancers.

In the Nov. 21 issue of the Archives of Dermatology, the researchers say the new test, which relies on the soluble adenylyl cyclase (sAC) expression pattern, provides objective results — if sAC is present in the nucleus of cells from a skin biopsy then, melanoma is present. If the nucleus is not positive, the sample is benign. Most diagnostic stains in use today highlight a specific cell in the biopsy; where the stain is more intense, it is more likely it is to be melanoma. However, how "intense" something stains is a subjective measurement.

"The sAC stain is either positive or negative in the cell's nucleus. Other stains require an interpretation of staining intensity, which means that a diagnosis of melanoma can rest on a pathologist's opinion," says senior author Dr. Jonathan Zippin, an assistant professor of dermatology at Weill Cornell Medical College.

"As a clinical dermatologist, this uncertainty is difficult to deal with," continues Dr. Zippin, who sees patients at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "No one wants to miss a true diagnosis of melanoma, but telling someone they have melanoma, when they may not, changes his or her life."

Diagnosing melanoma in a patient means that the skin lesion, and an area of healthy tissue around it, must be removed — surgery that can be disfiguring. Additionally, patients diagnosed with melanoma now have the added worry that they may develop another cancer, Dr. Zippin says, since patients diagnosed with a melanoma are at a higher risk for developing another cancer.

The study's lead author, Dr. Cynthia Magro, professor of pathology and laboratory medicine at Weill Cornell Medical College and a pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, suggests that the sAC stain should be used in conjunction with other diagnostic tests, such as light microscopy and the other three stains now available.

"What I hope is that five years down the line, this and other stains will help pathologists remove any uncertainty as to whether a biopsy is worrisome," says Dr. Zippin.

Dr. Magro says, however, that sAC provides one benefit that no other stain does. "The greatest practical application of sAC is using it to determine the cancer-free margins of a lentigo maligna that needs to be removed," she says. "This is a common melanoma in situ, usually found on the face, that does not show invasive growth. But until the development of sAC, it was very difficult to tell where the cancerous lesion ended." The sAC stain, which she uses on many patients, "is vastly superior to any other test we have now to determine margins."

The new stain is a monoclonal antibody that binds to sAC, which is a signaling molecule, says Dr. Zippin, who has long researched the molecule. "sAC senses changes in the interior of cells, such as pH and metabolism, and responds by regulating gene expression, metabolism and growth," he says.

Dr. Lonny Levin and Dr. Jochen Buck, both professors of pharmacology at Weill Cornell Medical College, discovered the sAC protein and developed the antibody that Dr. Zippin and Dr. Margo used to develop the diagnostic test. Based on the promise of this research, the four doctors created a company called CEP Biotech, Inc. to share the antibody with the scientific community. Currently, they are scientific advisers to the company and have no fiscal role.

"Because the sAC protein is expressed in all tissues of the body, and appears to be linked to processes important for the development of cancer, we predict this immunostain will be useful for the diagnosis of many other cancers and diseases," Dr. Zippin says.

While a diagnostic stain does not need FDA approval, the researchers say CEP Biotech, Inc. is planning on seeking federal approval of the sAC antibody as a diagnostic test.

Co-authors of the study include Dr. A. Neil Crowson of the University of Oklahoma and St. John Medical Center and Regional Medical Laboratory — both in Tulsa, Okla.; and Dr. Garrett Desman of the Laboratory of Dermatopathology in Port Washington, N.Y.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.