Prognostic significance of the tumor suppressor gene maspin in non-small cell lung cancer.
BACKGROUND
Maspin is a serpin protease inhibitor, which is known to suppress tumor progression in breast cancer and to be regulated by wild-type p53. This study was performed to elucidate the biologic significance of maspin expression in non-small cell lung cancer.


METHODS
To investigate whether maspin is involved in progression, clinicopathologic features, and prognosis of non-small cell lung cancer, we performed an immunohistochemical study using antimaspin antibody and identified the presence of maspin messenger ribonucleic acid in cancerous and noncancerous tissues by reverse transcription-polymerase chain reaction analysis. In addition, we evaluated p53 expression immunohistochemically on the serial sections.


RESULTS
Most adenocarcinoma and squamous cell carcinoma showed cytoplasmic staining pattern. The cytoplasmic positive rate was 77.8% (42 of 54 specimens) for the stage III group, and 36.2% (21 of 58 specimens) for the stage I group (p < 0.0001). Three-year survival rates after operation were 30.8% for the maspin-positive group and 71.1% for the maspin-negative group (p = 0.007). In multivariate analysis, immunohistochemical maspin expression in patients with non-small cell lung cancer was an independent prognostic factor for overall survival. No correlation between maspin and p53 expression in cancer cells could be observed. There was an average fourfold increase in maspin messenger ribonucleic acid levels in cancerous tissues compared with those of noncancerous tissues, and stage III cases exhibited significantly higher maspin messenger ribonucleic acid levels than stage I cases (p = 0.003).


CONCLUSIONS
The results of this study suggest that overexpression of maspin in cytoplasm may be a useful marker of tumor progression and unfavorable prognosis for overall survival in some patients with non-small cell lung cancer. Furthermore, maspin expression in cytoplasm appears to be unaffected by p53.
Hirai
Kyoji
K
Department of Surgery II, Nippon Medical School, Tokyo, Japan. ky-hirai@nms.ac.jp
Koizumi
Kiyoshi
K
Haraguchi
Shuji
S
Hirata
Tomomi
T
Mikami
Iwao
I
Fukushima
Mitsuhiro
M
Yamagishi
Shigeki
S
Kawashima
Tetsuo
T
Okada
Daisuke
D
Shimizu
Kazuo
K
Kawamoto
Masashi
M
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000401:mortality; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000378:metabolism / Q000401:mortality; D003593:Cytoplasm / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D015993:Life Tables; D008175:Lung Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015843:Serpins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C085344:SERPIN-B5; D015843:Serpins; D016159:Tumor Suppressor Protein p53