Immunohistochemical diagnosis of methylthioadenosine phosphorylase (MTAP) deficiency in non-small cell lung carcinoma.
Methylthioadenosine phosphorylase (MTAP) is involved in the metabolism of purines and converts methylthioadenosine (MTA) to adenine. It is abundant in all normal tissues but is deficient in various tumors. Here, we investigated MTAP deficiency in clinical samples of lung cancer using immunohistochemistry (IHC), and compared these results with those obtained by real-time PCR. Seventy-five samples were obtained from patients who underwent operations for non-small cell lung cancer (NSCLC). MTAP genetic analysis, using real-time PCR, and IHC were carried out on the samples. Methylation-specific primers were used to analyze methylation of the MTAP promoter, using DNA treated with sodium bisulfite. Sixty-nine of 75 samples were compared using both IHC and real-time PCR. The IHC results were consistent with those of real-time PCR in 56 samples. Of 62 positive samples tested by real-time PCR, only 49 (79%) were MTAP-positive by IHC. Seven samples were MTAP-negative by real-time PCR and IHC. In 13 samples of PCR (+) and IHC (-), six samples showed that the promoter region of MTAP was methylated. IHC is an accurate and useful diagnostic method for detecting MTAP deficiency in NSCLC, and the frequency of MTAP deficiency was found to be relatively high. The metabolic alterations diagnosed by IHC could be exploited for selective chemotherapy.
Department of Thoracic and Cardiovascular Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Fumiaki
F
Watanabe
Motoshi
M
Takao
Kentarou
K
Inoue
Junji
J
Nishioka
Tsutomu
T
Nobori
Taizo
T
Shiraishi
Masanori
M
Kaneda
Takashi
T
Sakai
Isao
I
Yada
Hideto
H
Shimpo
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000235:genetics*
D000911:Antibodies, Monoclonal; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase