Tumor Protein May Offer Potential for Early Diagnosis of LC

[Christine]

By Charles Bankhead, Staff Writer, MedPage Today

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

ATLANTA, Sept. 20 -- A protein expressed by virtually all lung cancers offers the potential for a serum biomarker that could lead to early diagnosis of more patients, investigators reported here.

Detectable serum levels of human aspartyl (asparaginyl) β-hydroxylase (HAAH) were identified in 99% of a group of lung cancer patients, but none were seen in a cancer-free control group, Mark Semenuk reported at a molecular diagnostics conference sponsored by the American Association for Cancer Research.

A serum test for HAAH "has great promise as an additional diagnostic tool for lung cancer, having the practicality and cost-effectiveness of conventional serologic screening," said Semenuk. "Elevated serum HAAH in conjunction with CT scanning may greatly facilitate early diagnosis of lung cancer at a stage in which cure rates are significantly higher and thus may contribute to increased patient survival."

Patients with lung cancer have a five-year survival of 15%. However, survival increases to 50% with early diagnosis. Unfortunately, only about 15% of lung cancer cases are diagnosed at earlier, more curable stages with current diagnostic methods.

A major obstacle to achieving better survival is the lack of a lab test for early diagnosis. X-ray and CT scanning are commonly used to diagnose lung cancer, but both imaging techniques have low sensitivity and higher cost compared with serologic techniques, Semenuk noted.

HAAH is elevated in a variety of cancers, including lung cancer. Laboratory studies have shown the enzyme is present in more than 99% of tumor specimens but absent in adjacent normal tissues. The protein's near-ubiquitous association with tumors made it attractive for evaluation as a lung cancer biomarker.

Semenuk and colleagues measured serum levels of HAAH in 160 patients with lung cancer, a control group of 93 people with no evidence of cancer, and 50 smokers with no evidence of cancer. Consistent with previous studies, HAAH was detected in serum samples from 99% of the lung cancer patients but none of the control group. Presence of the enzyme was associated with all cancer stages.

The average serum HAAH level was 0 ng/mL in the smokers. Four smokers had serum levels exceeding the diagnostic threshold of 3 ng/mL, although they were not known to have cancer. The assay had a 90% specificity in the smokers.

"We were encouraged by the low false-positive rate in smokers," said Semenuk. "Other serum cancer markers, such as CEA, are often elevated in smokers, leading to a high rate of false-positives."

Although the test is not yet available, physicians can submit samples and get test results for free. Instructions for submitting samples are available online at www.panacea-labs.com.

"Elevated levels of HAAH cannot confirm whether a person has lung cancer but can be used as a routine screening test for recommending further diagnostic evaluation," Semenuk emphasized.

Work has already begun to determine the utility of HAAH as a diagnostic test for prostate cancer. Such a test might be used as a follow-up lab assessment of men who have elevated PSA levels, Semenuk suggested. A positive HAAH test might then identify patients who should be biopsied.

Looking beyond the diagnostic potential of HAAH, Semenuk said the enzyme "has a lot of biology associated with it. It's not simply a marker that has no meaning other than being associated with cancer. The enzyme system is doing something in cancer cells, it could be subject to targeting for therapy."

Semenuk is an employee of Panacea Pharmaceuticals in Gaithersburg, Md., developer of the assay for HAAH.