Sputum Sampling May Provide Genetic Signs of Lung Cancer

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Sputum Sampling May Provide Genetic Signs of Lung Cancer

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nalysis of molecular genetic markers in biological fluids has often been proposed as a potential tool for cancer diagnosis.

Markers are needed for lung cancer in particular because the disease is notorious for presenting late in its course. Patients with new-onset lung cancer may be asymptomatic for months or even years before a persistent cough, shortness of breath, hemoptysis, or hoarseness motivates them to seek medical help.

In a new study published in Clinical Cancer Research by Li and colleagues at the University of Maryland School of Medicine,

the genetic signatures in primary non—small cell lung cancer have been characterized in detail. The investigators sought to determine whether genetic changes can be used as markers in sputum specimens for the early detection of lung cancer. Specifically, genetic aberrations in the genes HYAL2, FHIT, and SFTPC were evaluated in paired tumors and sputum samples

from 38 patients with stage I non—small cell lung cancer and in sputum samples from 36 cancer-free smokers and 28 healthy nonsmokers by using fluorescence in situ hybridization.

The results were impressive. HYAL2 and FHIT were deleted in 84% and 79% tumors and in 45% and 40% of paired sputum samples, respectively. SFTPC was deleted exclusively in tumor tissues (71%). There was concordance of HYAL2 or FHIT deletions in matched sputum and tumor tissues from lung cancer patients (P = 0.04 and P = 0.03, respectively), suggesting that the genetic changes in sputum could indicate the presence of the same genetic aberrations in lung tumors. Moreover, abnormal cells were found in 76% of sputum samples from cancer patients by detecting combined HYAL2 and FHIT deletions, and only in 47% of sputum samples from cancer patients analyzed by cytology. Hence, detecting the combination of HYAL2 and FHIT deletions had greater sensitivity than that of sputum cytology for establishing a diagnosis of lung cancer. In addition, HYAL2 and FHIT deletions in sputum were associated with a smoking history in both the cancer patients and the cancer-free smokers (both P < 0.05).

The investigators concluded that smoking-related HYAL2 and FHIT deletions in sputum may constitute diagnostic markers for early-stage lung cancer. If their hypothesis is supported by more definitive research, clinicians may one day have a valuable

tool with which to detect early lung tumors and, hopefully, be more likely to offer curative options to afflicted patients.

According to Feng Jiang, MD, PhD, a coinvestigator of the study, “Most heavy smokers never develop lung cancer, even though cells in their airways show genetic damage. The trick is to find the genes that are only cancer related.”

Jiang added, “There is an urgent need to develop reliable early diagnostic biomarkers for lung cancer that can be detected

noninvasively, and these two genes look to be great candidate markers for such a test. We need to validate our findings, of course, but we have shown that the genetic aberrations seen in sputum reflect the same genetic aberrations found in lung tumors, and that these molecular changes occur before any morphological changes can be seen in a cytology test.”