Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation
1Cancer Registry of Norway, Oslo, Norway
2Department of Gynecological Oncology, Rikshospitalet - Radiumhrnpitalet Medical Center, Oslo, Norway
3Department of Tumor Biology, Rikshospitalet - Radiumhospitalet Medical Center, Oslo, Norway
4Faculty of Medicine, University of Oslo, Norway
5Department of Pathology, Rikshospitalet - Radiumhospitalet Medical Center, Oslo , Norway
*Corresponding Author(s): T. Paulsen E-mail:
Objective: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants.
Methods: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry.
Results: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups.
Conclusions: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.
MMP-2, MMP-14, TIMP-2, VEFG, VEGFR-1, VEGFR-2; Ovarian neoplasm; Borderline tumor; Population-based; Epithelial; Noninvasive implants
T. Paulsen,A.H. Ree,J. Kærn,K. Kjærheim,A. Bassarova,A. Berner,T. Haldorsen,C. Trope,J.M. Nesland. Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation. European Journal of Gynaecological Oncology. 2007. 28(5);356-363.
[1] Sherman M.E., Berman J., Birrer M.J. et al.: "Current challenges and opportunities for research on borderline ovarian tumors" Hum. Pathol., 2004, 35, 961.
[2] Cancer in Norway 2004. Cancer Registry of Norway 2006.
[3] Paulsen T., Kaern J., Kjaerheim K. et al.: "Symptoms and referral of women with epithelial ovarian tumors". Int. J. Gynaecol. Ohstet., 2005, 88, 31.
[4] Eichhorn J.H., Bell D.A., Young R.H. et al.: "Ovarian serous borderline tumors with micropapillary and cribriform patterns: a study of 40 cases and comparison with 44 cases without these patterns". Am. J. Surg. Pathol., 1999, 23, 397.
[5] Prat J.: "Serous tumors of the ovary (borderline tumors and carcinomas) with and without micropapillary features". Int. J. Gynecol Pathol., 2003, 22, 25.
[6] Stetler-Stevenson W.G., Aznavoorian S., Liotta L.A.: "Tumor cell interactions with the extracellular matrix during invasion and metastasis". Annu. Rev. Cell. Biol., 1993, 9541.
[7] Turpeenniemi-Hujanen T.: "Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers". Biochimie, 2005, 87 (3-4), 287.
[8] Reuben P.M., Cheung H.S.: "Regulation of matrix metalloproteinase (MMP) gene expression by protein kinases". Front Biosci., 2006, 111199.
[9] Barnhill R.L., Piepkorn M.W., Cochran A.J. et al.: "Tumor vascularity, proliferation, and apoptosis in human melanoma micrometastases and macrometastases". Arch. Dermatol., 1998, 134, 991.
[10] Udagawa T., Fernandez A., Achilles E.G. et al.: "Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy". FASEB J., 2002, 16, 1361.
[11] Van den Steen P.E., Dubois B., Nelissen I. et al.: "Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9)". Crit. Rev. Biochem. Mol. Biol., 2002, 37, 375.
[12] Allan J.A., Docherty A.J., Barker P.J. et al.: "Binding of gelallnases A and B to type-I collagen and other matrix components" Biochem. J., 1995, 309 (Pt 1), 299.
[13] Murphy G., Crabbe T.: "Gelatinases A and B". Meth. Enzymol., 1995, 248470.
[14] Strongin A.Y., Collier I., Bannikov G. et al.: "Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease". J. Biol. Chem., 1995, 270, 5331.
[15] Bjorklund M., Koivunen E.: "Gelatinase-mediated migration and invasion of cancer cells". Biochim. Biophys Acta, 2005, 1755, 37.
[16] Woessner J.F. Jr.: "Matrix metalloproteinases and their inhibitors in connective tissue remodeling". FASEB J., 1991, 5, 2145
[17] Lehti K., Lohi J., Valtanen H. et al.: "Proteolytic processing of membrane-type-I matrix metalloproteinase is associated with gelatinase A activation at the cell surface". Biochem. J., 1998, 334 (Pt 2), 345.
[18] Nakayama K., Takebayashi Y., Nam如T. et al.: "Comprehensive allelotype study of ovarian tumors of low malignant potential: potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma". Int. J. Cancer, 2001, 94 (4), 605.
[19] Gadducci A., Viacava P., Cosio S. et al.: "Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma". Anticancer Res., 2003, 23 (3C), 3001.
[20] Ramakrishnan S., Subramanian I.V., Yokoyama Y. et al.: "Angiogenesis in normal and neoplastic ovaries". Angiogenesis, 2005, 1.
[21] Bamberger E.S., Perrett C.W.: "Angiogenesis in epithelian ovarian cancer". Mot. Pathol., 2002, 55, 348.
[22] Wu M., Xu G., Xi L. et al.: "Down-regulation of MTl-MMP expression suppresses tumor cell invasion in metastatic human SW626 ovarian cancer cells". Oneal. Rep., 2006, 15, 501.
[23] Tumors of the Ovaries and Peritoneum. In: Tavassoli F.A., Devilee P. (eds.). Pathology & Genetics Tumours of the Breast and Female Genital Organs. I" edition, Lyon: I ARC Press, 2003, 113.
[24] Seidman J.D., Soslow R.A., Vang R. et al.: "Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images". Hum Pathol., 2004, 35 (8), 918.
[25] Ortiz B.H., Ailawadi M., Colitti C. et al.: "Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors". Cancer Res., 2001, 61, 7264.
[26] Gu J., Roth L.M., Younger C. et al.: "Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential". J. Natl Cancer Inst., 2001, 93, 1147.
[27] Shih I.,Kurman R.J.: "Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis". Am. J. Pathol., 2004, 164, 1511.
[28] Shih I., Kurman R.J.: "Molecular pathogenesis of ovarian borderline tumors: new insights and old challenges". Clin. Cancer Res., 2005, 11, 7273.
[29] Gotlieb W.H., Chetrit A., Menczer J. et al.: "Demographic and genetic characteristics of patients with borderline ovarian tumors as compared to early stage invasive ovarian cancer". Gynecol. Oncol., 2005, 97, 780.
[30] Makar A.P.,B aekelandt M.,T rope C.G. et al.: "The prognostic significance of residual disease,F IGO substage,t umor histology,and grade in patients with FIGO Stage III ovarian cancer". Gynecol. Oncol., 1995, 56, 175.
[31] Bell K.A., Smith S.A., Kurman R.J.: "Refined diagnostic criteria for implants associated with ovarian atypical proliferative serous tumors (borderline) and micropapillary serous carcinomas". Am. J. Surg. Pathol., 2001, 25, 419.
[32] Altman D.G.: "Practical Statistics for Medical Research". 1" edition, London: Chapman & Hall, 1991.
[33] Sounni N.E., Devy L., Hajitou A. et al.: "MTl-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression". FASEB J., 2002, 16, 555.
[34] Belotti D., Paganoni P., Manenti L. et al.: "Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation". Cancer Res., 2003, 63, 5224.
[35] Ogawa S., Kaku T., Kobayashi H. et al.: "Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma". Cancer Lett., 2002, 176, 111.
[36] Maatta M., Santala M., Soini Y. et al.: "Matrix metalloprotemases 2 and 9 and their tissue inhibitors in low malignant potential ovarian tumors". Tumour Biol., 2004, 25, 188.
[37] Garzetti G.G., Ciavattini A., Lucarini G. et al.: "Expression of vascular endothelial growth factor related to 72-kilodalton metalloproteinase immunostaining in patients with serous ovarian tumors". Cancer, 1999,8 5, 2219.
[38] Davidson B., Goldberg I., Gotlieb W.H. et al.: "High levels of MMP-2, MMP-9, MTI-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma". Clin. Exp. Metastasis, 1999, 17, 799.
[39] Davidson B., Goldberg I., Gotlieb W.H. et al.: "The prognostic value of metalloproteinases and angiogenic factors in ovarian carcinoma". Mol. Cell. Endocrinol., 2002, 187, 39.
[40] Lengyel E., Schmalfeldt B., Konik E. et al.: "Expression of latent matrix metalloproteinase 9 (MMP-9) predicts survival in advanced ovarian cancer". Gynecol. Oncol., 2001, 82, 291.
[41] Wu X., Li H., Kang L. et al.: Acti .: "Activated matrix metalloproteinase- 2-a potential marker of prognosis for epithelial ovarian cancer". Gynecol. Oneal., 2002, 84, 126.
[42] Monig S.P., Baldus S.E., Hennecken J.K. et al.: "Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma". Histopathology, 2001, 39, 597.
[43] Mendes 0., Kim H.T., Stoica G.: "Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model". Clin. Exp. Metastasis, 2005, 22, 237.
[44] Davidson B., Konstantinovsky S., Nielsen S. et al.: "Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression". Clin. Cancer Res., 2004, 10, 7335.
[45] Sier C.F., Kubben F.J., Ganesh S. et al.: "Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma". Br. J. Cancer, 1996, 74,413.
[46] Wollina U., Hipler U.C., Knoll B. et al.: "Serum matrix metalloproteinase-2 in patients with malignant melanoma". J. Cancer Res. Clin. Oncol., 2001, 127, 631.
[47] Singer G., Oldt R. III, Cohen Y. et al.: "Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma". J. Natl. Cancer Inst., 2003, 95, 484.
[48] Gilks C.B.: "Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases". Int. J. Gynecol. Pathol., 2003, 22, 29.
[49] Zanetta G., Rota S., Chiari S. et al.: "Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study". J. Clin. Oncol., 2001, 19, 2658.
[50] Matrisian L.M., Sledge G.W. Jr., Mohla S.: "Extracellular proteolysis and cancer: meeting summary and future directions". Cancer Res., 2003, 63, 6105.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top