Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma.
BACKGROUND
Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma.


METHODS
This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1.


RESULTS
The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor.


CONCLUSIONS
These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.
Yukiue
H
H
Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, 467-8601, Nagoya, Aichi, Japan.
Sasaki
H
H
Kobayashi
Y
Y
Nakashima
Y
Y
Moriyama
S
S
Yano
M
M
Kaji
M
M
Kiriyama
M
M
Fukai
I
I
Yamakawa
Y
Y
Fujii
Y
Y
D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics; D013945:Thymoma / Q000378:metabolism* / Q000473:pathology*; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020782:Matrix Metalloproteinases