Researchers in India have determined that sputum samples can be used to detect early stage lung cancer with high sensitivity and can predict prognoses for nonsmall cell lung cancer (NSCLC). The results were published in the Asian Pacific Journal of Cancer Prevention.
Lung cancer is the leading cause of cancer mortality worldwide; poor survival can be attributed to a diagnosis in the late stages of disease. Currently, sputum cytology has very low sensitivity due to an inadequate number of cells and variability of laboratory processing methods.
This study aimed to identify and characterize premalignant and malignant cells in sputum samples from patients with NSCLC. The research team used the marker proteins minichromosome maintenance proteins (MCM2, MCM5) and cell division cycle protein 6 (CDC6) and to evaluate their potential as biomarkers of lung lesions.
“The assessed markers can be utilized in routine cytopathology laboratories to supplement conventional morphological evaluation so that the sensitivity of sputum cytology can be enhanced,” wrote the investigators, led by VS Veena, MSc, from the Division of Pathology at the Regional Cancer Centre of the Medical College Campus in Thiruvananthapuram, India.
More than 3,000 patients were selected for the study from a cohort with chronic obstructive pulmonary disease or radiologic finding suspicious of malignancy. Sputum samples were matched with bronchoscopic biopsy samples and evaluated for expression of MCM2, MCM5, and CDC6 proteins.
MCM proteins are a good indicator of proliferative potential of cancer tissue because they are more frequently detected in cells from malignant tissues than in normal tissue. In this study, the MCM proteins showed intense expression in atypical and malignant cells, but weak positivity in normal tissue.
When assessing the correlation of clinical and pathological features with protein expression, the researchers found that MCM5 proteins showed significant correlation with tumor state, histologic type of tumor, and metastasis, while the MCM2 proteins correlated with tumor stage only. CDC6 was not evaluated because it had no significant association with clinicopathological features.
Further research is needed to determine if the increase in the expression pattern correlates with progression of the disease.
The scientists also analyzed the sensitivity of proteins in sputum samples as a predictive marker for premalignant and malignant lesions. While all proteins tested had sensitivity for diagnosis of malignancy, CDC6 was highest (58% for MCM2, 66% for MCM5, and 87% for CDC6). When taken together, the sensitivity improved further (93% for combined MCM2/CDC6, and 94% for both MCM2/CDC6 and MCM5/CDC6).
Cytology samples from sputum and tissue samples had the same expression pattern and sensitivity.
The authors state that the study characterized the malignant, metaplastic, and dysplastic cells of respiratory epithelium with MCM and CDC6 proteins, and that these markers could be used to screen for lung cancer.
In addition, the significant association of over-expression of these proteins with the stage of disease and metastasis has a potential application for predicting the clinical behavior of lung lesions.
To read more about this study, click here.