Emi Machida

Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non-small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease.

A Complete Response Case of Liver Metastasis from Primary Lung Cancer by Hepatic Arterial Infusion Chemotherapy

症例は64歳の男性で, 左肺上葉原発扁平上皮癌に対して上葉切除術を行った.術前の腹部CT検査で肝に孤立性の腫瘤陰影を認め, 術後4週の再検査で増大していたため, 肝転移と診断して肝動注化学療法 (MMC 2mg/日, VDS1mg/日, CDDP20mg/日を3円連続投与し1サイクルとした) を行った.3サイクル施行後には腫瘤は消失し, 6サイクルで終了した.肺癌手術2年5カ月後に行われた早期胃癌手術時の術中超音波検査では, 肝に腫瘤は認めなかった.肺切除後3年10カ月を経た現在, 肝のみならず胸腔内や他臓器への再発の徴候は認めず健在である.原発性肺癌肝転移に対して, 肝動注化学療法は本例のように有効な症例もあり, 可能ならば試みるべき方法と考える.