Expression of H IF21 and MM P22 in va sculogen ic m im icry of ovar ian cancer. Su M in 1,

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1 H IF21 MMP22 3 1, 133, 2, 2, 3, 1 (1. ; 2. ; 3., ) :H IF21MMP22 (VM ) : , H IF21 MMP22,CD34 PAS VM,H IF21 MMP22 VM : H IF21( r = , P = ) ( r = , P = ),MMP22( r = , P = ) VM ( P = ), VM VM H IF21 ( P = ), VM MMP2 2( P = ) : VM, H IF21 MMP2 2 VM 1 ; 2; ; : R : A : (2011) Expression of H IF21 and MM P22 in va sculogen ic m im icry of ovar ian cancer. Su M in 1, Zhang Yuquan 1, Huang Hua 2, et al. 1. D epartm ent of O bstetrics and Gynecology; 2. D epartm ent of Pathology, the A ffiliated Hospital of N angtong U n iversity, N antong Abstract O bjective: To investigate the relationship between exp ression of hypoxia in2 duced factor21 ( H IF21 ), matrix metallop roteinase22 (MMP22 ) and vasculogenic m im icry (VM ). M ethods: 81 paraffin2embedded sections of ovarian tumor were studied. Exp ression of H IF21 and MMP22 were detected by immunohistochem ical staining. The p resence of VM was observed by histochem ical double staining of CD34 and PAS. Relationship between exp ression of H IF21,MMP22 and VM were discussed. Results: Positive exp ressions of H IF21 and MMP2 2 p rotein were detected in ovarian cancer. Vasculogenic m im icry, when PAS was positive but CD34 was negative, appeared in some cases of ovarian cancer. Positive correlation was observed between tumor grade and VM ( P = ). Positive relationship was found between exp ression of H IF21 and clinical stage ( r = , P = ), grade ( r = , P = ). Positive re2 lationship was also found between exp ression of MMP22 and grade ( r = , P = ). Ex2 p ression of H IF21 ( P = ) and MMP22 ( P = ) in ovarian cancer with VM were in2 creased significantly than those w ithout VM. Conclusion:Vasculogenic m im icry exists in ovari2 an cancer, especially in the lower grade. Exp ression of H IF21 and MMP22 are associated with tumor grade and form ation of vasculogenic m im icry. Key wordshypoxia induced factor21 ; Matrix metallop roteinase22; Ovarian neo2 p lasm s; Vasculogenic m im icry (No: S ) ; (No: ) jsnt_zhangyuquan@ yahoo. com. cn 83

2 ( vasculogenic m im icry, VM ) [ 1 ],,,, Maniotis [ 2 ] PAS,,,, PAS CD34 /CD31 VM [ 3 ], H IF21 VM [ 3 ] H IF21, H IF21, H IF21 [ 4 ],H IF21 [ 5 ] 2 (MMP22) [ 6 ],MMP2 2 VM [ 3 ],CD34 PAS VM,H IF21MMP22,H IF21 MMP22 VM, H IF21 MMP22VM ( + ) VM ( - ) , 13 81, 52 : ; ; ; WHO, 24,22, 26, 9 ( F IGO) 2000, 35 13, 18, 4 ;, ( G 1 ) 4, ( G 2 ) 17, ( G 3 ) CD34, H IF21 MMP22 (), (DAKO), ABC ( ) PAS H IF21MMP m,,, 3% H 2 O 2,, 10%, H IF21MMP22 2h, 30m in, DAB,, H IF2 1, MMP22,, Formwitz, 5, : 5% 0, 25% 1, 50% 2, 75% 3, > 75% 4 : 0, 1, 2, 3 : 0 ( - ) ; 1 4( + ) ; 5 8 ( + + ) ; 9 12( ) CD34 /PAS CD34 ( PAS) VM CD34 DAB,,, 0. 5% 8 10m in, Schiff 10m in,,, PAS CD34,, PAS, CD34,, VM :, ( 400) SPSS16. 0, 2, wilcoxon, Spearman s Kap lan2meier,log2rank H IF21 MMP22 H IF21 MMP22,1Fisher s, H IF21 MMP22 ( 2 = , P = ; 2 = , P = ), 81, H IF21 40, 49. 4% H IF % (29 /35) 45. 5% (10 /22) 4. 2% (1 /24), H IF21 ( F = , P < 0. 01), SN K,( P < 0. 05) 81 MMP22 50, 61. 7% H IF21

3 74. 3% (26 /35) 63. 6% (14 /22) 41. 7% ( 10 / 24), MMP22 ( F = , P = ) ; SN K, MMP22 ( P < 0. 05), MMP22, ( P > 0. 05) 1 Spearman, H IF21( r = , P = ) ( r = , P = ) ;MMP22 ( r = , P = ), ( r = , P = ) 1 1H IF21 MMP22 n H IF P MMP P < G G G CD34 /PAS VM, PAS,, PAS, CD34,,,;,2 VM 46. 2% ( 6 /13 ) 38. 9% ( 7 /18 ) 50. 0% ( 2 /4 ), W ilcoxon, VM ( z = , P = ) G 1 G 2 G 3 VM 0. 0% (0 / 4) 35. 3% (6 /17) 64. 3% (9 /14), W ilcoxon, VM ( z = , P = ), VM 2. 3 H IF21 MMP22 VM VM H IF21, 78. 9% ; VM6225 H IF21, 40. 3% ;, VMH IF21 VM ( 2 = , P = ), VMH IF21 ( 2 = , P = ), VMH IF21 ( 2 = , P = ) VM MMP22, 89. 5% ; VM62 33, 53. 2% ;, MMP22 VM( 2 = , P = ), VM MMP22( 2 = , P = ), VM MMP22 ( 2 = , P = ) 2 2 H IF21 MMP22VM n H IF21 MMP22 VM VM Spearman, VM H IF21 ( r = , P = ) ; VM MMP22 ( r = , P < 0. 01) VM H IF21 MMP22 VM,3 85

1 H IF21 MMP22 (DAB 400) A: H IF21; B:MMP22 2 VM CD34 /PAS ( 400) : VM; : 3 VM VM H IF21

4 H IF21 MMP22 VM ( + ) VM ( - ) 35,2010 5 VM15 39 (31. 426 46. 574), VM20 68 (52. 661 83.

01 ),4 Kap lan2meier : VM ( + ), H IF21 MMP22 ( P > 0. 05) ; VM ( - ), H IF21 MMP22 ( P > 0.

4 1 H IF21 MMP22 (DAB 400) A: H IF21; B:MMP22 2 VM CD34 /PAS ( 400) : VM; : 3 VM VM H IF21 MMP22(DAB 400) A: VM H IF21 ; B: VM H IF21 ; C: VM MMP22 ; D: VM MMP H IF21 MMP22 VM ( + ) VM ( - ) 35, VM15 39 ( ), VM20 68 ( ); Kap lan2meier VM VM, Log2rank, ( P < ),4 Kap lan2meier : VM ( + ), H IF21 MMP22 ( P > 0. 05) ; VM ( - ), H IF21 MMP22 ( P > 0. 05) VM VM Kap lan2meier 3. 1 VM VM,,,,,PAS,, CD34,VM,,, VM, VM, VM, VM,, VM, VM VM,,, 3. 2 H IF21 VM,, H IF21 H IF, (H IF21 ) ( H IF21 ) H IF21, H IF21O 2,, VEGF,

5 [ 7 ], H IF21, [ 8 ] H IF21, H IF21,, VEGF, H IF21,,,H IF21 VEGF, VM [ 9 ], H IF21, H IF21,H IF2 1, VM, H IF21 VM VM H IF21,VM H IF21 VM, SunVM H IF21 [ 3 ] H IF21 H IF21,,,,,,, VM 3. 3 MMP22VM MMP22,,,,,MMP22, VM VM,MMP22 VM [ 3 ] Anil [ 10 ], MMP21, MMP22, MMP29, MT12MMP,MMP VM MMP22, VM MMP22,MMP22 VM MMP22,,,, VM VM, VM VM,MMP22 H IF21,, VM, H IF21 MMP22,, H IF21 MMP22 VM VM,H IF21 MMP22 VM, [ 1 ] Scavelli C, N ico B, Cirulli T, et al. Vasculogenic m im icry by bone marrow macrophages in patients with multip le myeloma[ J ]. Oncogene, 2008, 27 ( 5) : [ 2 ] Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic m im icry[ J ]. Am J Pathol, 1999, 155 ( 3) : [ 3 ] Sun BC, Zhang DF, Zhang SW, et al. Hypoxia influences vasculogenic m im icry channel formation and tumor inva2 sion2related p rotein exp ression in melanoma [ J ]. Cancer Letters, 2007, 249 ( 6) : [ 4 ] Daponte A, Ioannou M,Mylonis I, et al. Prognostic signifi2 cance of hypoxia2inducible factor 1 alpha ( H IF21 alpha) exp ression in serous ovarian cancer: an immunohistochem2 ical study[ J ]. BMC Cancer, 2008, 16 (8) : 335 [ 5 ] Yao LQ, Feng YJ, D ing JX, et al. D ifferentiation of vascu2 lar endothelial cells2like derived from ep ithelial ovarian cancer cells induced by hypoxia[ J ]. Int J Oncol, 2007, 30 (5) : [ 6 ] Zheng H, Takahashi H,Murai Y. Exp ressions of MMP22, MMP29 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [ J ]. An2 ticancer Res, 2006, 26 (5A) : [ 7 ] Zhang S, Gun H, Zhang D, et al. M icrocirculation patterns in different stages of melanoma growth [ J ]. Oncol Rep, 2006, 15 (1) : [ 8 ] PhaniMG, Theresa LW, CheungW, et al. Cytokine regula2 tion of H IF21 alpha in ovarian cancer[ J ]. Proc Am A ssoc Cancer Res, 2006, 47 (6) : [ 9 ] Su M, Yao LQ, Feng YJ, et al. Plasticity of ovarian cancer cell and vasculogenic m im icry in vivo [ J ]. Int J Gynecol Cancer, 2008, 18 (3) : [ 10 ] Anil KS,Mavis S, Fletcher MD, et al. Functional role of matrix metallop roteinases in ovarian tumor cell p lasticity [ J ]. Am J Obstet Gynecol, 2004, 190 (4) : ( ) :(19762),, : 87

Medical Journal of National Defending Forces in North China, Dec. 2008, Vol. 20, No. 6

2008 12206 Medical Journal of National Defending Forces in North China, Dec. 2008, Vol. 20, No. 6 23 1, 2, 2 (11, 215300; 21, 226001) [] : (OPN)23 (MMP23) :Eliviion 54 OPN MMP23, 34, 10,10 ; OPN MMP23