The detection of peripheral lung cancer by MAGE A1-6 RT-nested PCR in bronchial washing specimens.
BACKGROUND
With expansion of lung cancer screening by computed tomography (CT) and increased incidence of adenocarcinoma, we encountered more peripheral nodules to be identified. We evaluated detection rates of the melanoma antigen genes (MAGE) RT-nested PCR using a common MAGE A1-6 primer in bronchoscopic washing samples from patients with bronchoscopically invisible peripheral nodules, and compared with those of conventional cytology and percutaneous needle aspiration biopsy (PCNB).


METHODS
Forty-two patients with bronchoscopically invisible peripheral lung nodules were studied. Bronchoscopic washing specimens were collected by instilling 20ml of normal saline into a tumor bearing segment and retrieving samples. Samples were split and analyzed by MAGE RT-PCR and conventional cytology. A PCNB was performed in all but two patients. Twenty-eight lesions were diagnosed as lung cancers and 14 as benign lung diseases. We evaluated MAGE A1-6 RT-nested PCR, cytology, and PCNB results and analyzed them according to histologic cell types and tumor sizes.


RESULTS
In bronchial washing samples, the detection rates of MAGE A1-6 RT-nested PCR (67.9%) were higher than that of conventional cytology (21.4%, p=.04) and similar to that of PCNB (73.1%, p=.45) in 28 cancer patients. In terms of histologic types, the detection rates of MAGE A1-6 RT-nested PCR, conventional cytology, and PCNB were 78.6%, 21.4% and 64.3% in adenocarcinoma, 70%, 20% and 77.8% in squamous cell carcinoma, respectively. The sensitivity of conventional cytology was significantly lower than that of MAGE RT-nested PCR or PCNB regardless of tumor histology p=.04, p=.025, respectively, in adenocarcinoma; p=.035, p=.04, respectively, in squamous cell carcinoma). In terms of tumor size, the corresponding detection rates were 73.3%, 6.7% and 73.3% for tumors smaller than 3cm (N=15), and 61.5%, 38.5% and 72.7% for tumors larger than 3cm (N=13).


CONCLUSIONS
MAGE A1-6 RT-nested PCR showed higher detection rates in the bronchial washes of peripheral lung cancer patients than conventional cytology testing. This method is simple and robust, and it could be effectively utilized as a peripheral lung cancer detection tool in clinical laboratories.
Kim
Hyeong Ryul
HR
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South Korea.
Kim
Tae Hun
TH
Chung
Jin-Haeng
JH
Yoon
Ho Il
HI
Lee
Choon Taek
CT
Kang
Chang Hyun
CH
Jheon
Sanghoon
S
Sung
Sook Whan
SW
Kim
Joo Hyun
JH
Jeon
Changho
C
D000951:Antigens, Neoplasm / Q000032:analysis*; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D055088:Early Detection of Cancer; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C095203:MAGEA6 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins