Expression of Matrix Metalloproteinases in Patients With Uterine Smooth Muscle Tumors: An Immunohistochemical Analysis of MMP-1 and MMP-2 Protein Expression in Leiomyoma,Uterine Smooth Muscle Tumor of Uncertain Malignant Potential,and Leiomyosarcoma

Abstract

Objective: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis. We compared the expression of MMP-1 and MMP-2 protein in patients with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS).

Methods: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS.

Results: MMP-1 was expressed in 92% of leiomyomas, in 83% of STUMP, and in 86% of LMS, whereas MMP-2 was expressed in 12% of leiomyomas, in 17% of STUMP, and in 48% of LMS. A statistically significant difference regarding the frequency of MMP-2 expression was observed between LMS and STUMP (P = .025) as well as between LMS and leiomyoma (P = .006), but not between STUMP and leiomyoma (P > .05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma (P = .025), but no statistical significant difference was observed between LMS and STUMP (P > .05) and between STUMP and leiomyoma (P > .05).

Conclusion: The stronger MMP-2 expression in patients with LMS compared with STUMP and leiomyoma indicates that this protein might be a marker for tumor invasion or metastasis in patients with uterine LMS. Furthermore, MMP-2 seems to be a useful immunohistochemical parameter to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline. Further studies including larger numbers of patients are necessary to establish MMP-2 as a routine marker for tumor invasion and progression.

Keywords

Uterine leiomyosarcoma uterine smooth muscle tumor of uncertain malignant potential leiomyoma MMP-1 MMP-2 expression

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References

1. Djonov V , Cresto N , Aebersold DM , et al. Tumor cell specific expression of MMP-2 correlates with tumor vascularisation in breast cancer. Int J Cancer 2002;21(1):25-30.

2. Stetler-Stevenson WG . Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix. Am J Pathol 1996;148:1345-1350.

3. Jones JL , Walker RA . Control of matrix metalloproteinase activity in cancer. J Pathol 1997;183:377-379.

4. Kikkawa F , Nawa A , Shibata K , et al. The different stimulatory effect of normal tissues on the secretion of matrix metalloproteinases and their inhibitors of human ovarian cancer cell lines. Anticancer Res 1998;18:4323-4328.

5. Brummer O , Böhmer G , Hollwitz B , Flemming P , Petry K , Kühnle H . MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation—An immunhistochemical study. Gynecol Oncol 2002;84:222-227.

6. Vegh GL , Tuncer ZS , Fulop V , Genest DR , Mok SC , Berkowitz RS . Matrix metalloproteinases and their inhibitors in gestational throboblastic disease and normal placenta. Gynecol Oncol 1999;75:248-253.

7. Zhai YL , Nikaido T , Toki T , Shiozwawa A , Orii A , Fijii S . Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus. Br J Cancer 1999;80(10):1658-1664.

8. Mittal K , Demopoulos RI . MIB-1 (KI-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Hum Pathol 2001;32(9):984-987.

9. Clement PB . The pathology of uterine smooth muscle tumors and mixed endometrial stromal smooth muscle tumors: A selective review with emphasis on recent advances. Int J Gynecol Pathol 2000;19:39-55.

10.

10. Zaloudek CJ , Norris HJ . Mesenchymal tumors of the uterus. In: Kurman RJ , ed. Blaustein's pathology of the female genital tract. New York: Springer Verlag, 1994:849-914.

11.

11. Vollenhoven BJ , Lawrence AS , Healy DL . Uterine fibroids: A clinical review. Br J Obstet Gynecol 1990;97:285-298.

12.

12. Bodner-Adler B , Bodner K , Kimberger O , Czerwenka K , Leodolter S , Mayerhofer K . MMP-1 and MMP-2 expression in uterine leiomyosarcoma and correlation with different clinico-pathologic parameters. J Soc Gynecol Investig 2003;10:443-446.

13.

13. Bell SW , Kempson RL , Hendrickson MR . Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Pathol 1994;18(6):535-558.

14.

14. Zucker S , Lysik RM , Zarrabi MH , Moll U . M(r) 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer Res 1993;53:140-146.

15.

15. Herbst H , Wege T , Milani S , et al. Tissue inhibitor of metallo-proteinases -1 and -2 expression in rat and human liver fibrosis. Am J Pathol 1997;150:1647-1659.

16.

16. Huhtala P , Chow LT , Tryggvason K . Structure of human type IV collagenase gene. J Biol Chem 1990;265:11077-11082.

17.

17. Dou Q , Tarnuzzer RW , Williams RS , Schultz GS , Chegini N . Differential expression of matrix metalloproteinases and their tissue inhibitors in leiomyomata: A mechanism for gonadotrophin hormone agonist-induced tumor regression. Mol Hum Reprod 1997;3:1005-1014.

18.

18. Sozen I , Arici A . Interactions of cytocines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata. Fertil Steril 2002;78(1):1-12.