MMP7 and YKL-40 expressions in endometrial endometrioid carcinomas

Purpose of investigation: The expressions of YKL-40, MMP-7 and their relations with prognostic factors in endometrioid endometrial carcinomas (EEC) were investigated. Materials and Methods: Paraffin blocks of 50 patients diagnosed with EEC, 27 patients with endometrial hyperplasia, and 26 patients with normal cyclic endometrium were determined and the immunohistochemical staining (IHS) results of MMP-7 and YKL-40 antibodies were obtained. These results were compared with prognostic parameters with statistical evaluation. Results: Score 1 immunostaining was observed in 13 (26%), score 2 in 12 (24%), score 3 in 9 (18%), score 4 in 5 (10%) with MMP-7 in EEC. There was no MMP-7 expression in 9 (% 18) cases in carcinoma group. There was no statistically significant difference in proliferative and secretory phases in normal cycle group (p = 0.527). There was also no statistically significant difference between the non-typical and atypical hyperplasia/EIN cases (p = 0.42). Positive immunostaining was obtained in 15 (58%) of 26 normal cyclic endometrium, in 21 (78%) of 27 hyperplastic endometrium, in 19 (38%) of 50 EEC with YKL-40. The differences of YKL-40 expressions among all the groups were statistically significant (p =0.01)). MMP-7 and YKL-40 expressions were compared with clinicopathologic parameters in the carcinoma group and found no statistical significant difference (p > 0.05). Conclusion: The present findings were limited but suggested that MMP-7 and YKL-40 might play a role in tumor progression.

Endometrioid endometrial carcinoma; YKL-40; MMP-7; Immunohistochemistry

[1] Siegel R, Naishadham D, Jemal A.: “Cancer statistics”. Cancer J. Clin., 2013, 63, 11.

[2] Tuncer A.M. “Türkiyede Kanser Kontrolü”. Ankara: Sağlık Bakanlığı Yayınları, 2009.

[3] Graesslin O., Cortez A., Fauvet R., Lorenzato M., Birembaut P., Darai E. “Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2 expression in normal, hyperplastic and neoplastic endometrium:a clinical-pathological correlation study”. Ann. Oncol., 2006, 17, 637.

[4] Wojtowicz-Praga S.M., Dickson R.B., Hawkins M.J. “Matrix metalloproteinase inhibitors”. Invest. New Drugs., 1997, 15, 61.

[5] Ray J.M., Stetler-Stevenson W.G. “The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis”. Eur. Respir. J., 1994, 7, 2062.

[6] Rodgers W. “Matrix metalloproteinases and carcinogenesis”. Hum. Pathol., 1999, 30, 363.

[7] Mcdonnell S., Nnavre M., Coffey R.J. Jr., Matrisian L.M. “Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas”. Mol. Carcinog., 1991, 4, 527.

[8] Muller D., Breathnach R., Engelman A., Millon R., Mronner G., Mıllon R., Mronner G., Flesch H., et al.: “Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumors”. Int. J. Cancer, 1991, 48, 550.

[9] Knox J.D., Wolf C., Mcdaniel K., Clark V., Lorıot M., Bowden G.T., et al.: “Matrilysin expression in human prostate carcinoma”. Mol. Carcinog., 1996, 15, 57.

[10] Johansen J.S., Williamson M.K., Rice J.S., Price P.A. “Identification of proteins secreted by human osteoblastic cells in culture”. J. Bone Miner. Res., 1992, 7, 501.

[11] Johansen J.S., Jensen H.S., Price P.A. “A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid”. Br. J. Rheumatol., 1993, 32, 949.

[12] Vind I, Johansen J.S., Price P.A., Munkholm P.: “Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease”. Scand. J. Gastroenterol., 2003, 38, 599.

[13] Johansen J.S., Jensen B.V., Roslind A., Nielsen D., Price P.A. “Serum YKL-40, a new prognostic biomarker in cancer patients?” Cancer Epidemiol. Biomarkers Prev., 2006, 15, 194.

[14] Renkema G.H., Boot R.G., Au F.L., Donker-Koopman W.E., Strijland A., Muijsers A.O., et al.: “Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages”. Eur. J. Biochem., 1998, 251, 504.

[15] Fusetti F., Pijning T., Kalk K.H., Bos E., Dijkstra B.W.: “Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39”. J. Biol. Chem., 2003, 278, 37753–37760.

[16] Peng C., Peng J., Jiang L., You Q., Zheng J., Ning X.: “YKL-40 Protein Levels and Clinical Outcome of Human Endometrial Cancer”. J. Int. Med. Res., 2010, 38, 1448.

[17] Prat J.: “Prognostic parameters of endometrial carcinoma”. Hum. Pathol., 2004, 35, 649.

[18] Soini Y., Alarakkola E., Auto-Harmainen H.: “Expression of messenger RNAs for metalloproteinases 2 and 9, type IV collagen, and laminin in nonneoplastic and neoplastic endometrium”. Hum. Pathol., 1997, 28, 220.

[19] Maata M., Soini Y., Liakka A., Autio-Harmainen H.: “Localization of MT1-MMP, TIMP-1, TIMP-2 and TIMP-3 messenger RNA in normal, hyperplastic and neoplastic endometrium. Enhanced expression by endometrial carcinomas is associated with low differentiation”. Am. J. Clin. Pathol., 2000, 114, 402.

[20] Mutter G.L., Boynton K.A., Faquin W.C., Ruiz R.E., Jovanovic A.S.: “Allelotype mapping of instable microsatellites establishes direct lineage continuity between endometrial precancers and cancer”. Cancer Res., 1996, 56, 4483.

[21] Misugi F., Sumi T., Okamoto E., Nobeyama H, Hattori K, Yoshida H., et al.: “Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis”. Int. J. Mol. Med., 2005, 16, 541.

[22] Ueno H., Yamashita K., Azumano I., Inoue M., Okada Y.: “Enhanced Production and Activation of Matrix Metalloproteinase-7 (Matrilysin) in Human Endometrial Carcinoma”. Int. J. Cancer, 1999, 84, 470.

[23] Monaghan H., MacWhinnie N., Williams A.R.W.: “The role of matrix metalloproteinases-2, -7 and -9 and b-catenin in high grade endometrial carcinoma”. Histopathology, 2007, 50, 348.

[24] Goffin F., Munaut C., Frankenne F., Perrier D’Hauterive S., Béliard A., Fridman V., et al.: “Expression pattern of metalloproteinasesand tissue inhibitors of matrix-metalloproteinases in cycling human endometrium”. Biol. Reprod., 2003, 69, 976.

[25] Salamonsen L.A., Zhang J., Hampton A., Lathbury L.: “Regulation of matrix metalloproteinases in human endometrium”. Hum. Reprod., 2000, 15, 112–119.

[26] Wilson C.L., Matrisian L.M.: “An epithelial matrix metalloproteinase with potentially novel functions”. Int. J. Biochem., 1996, 28, 123–136.

[27] Laas E., Ballester M., Cortez A., Gonin J., Canlorbe G., Daraï E., Graesslin O.: “Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia”. Gynecol. Endocrinol., 2015, 31, 282.

[28] Wang F.Q., So J., Reierstad S., Fishman D.A.: “Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase”. Int. J. Cancer, 2005, 114, 19.

[29] Johansen J.S., Schultz N.A., Jensen B.V.: “Plasma YKL-40: a potential new cancer biomarker”. Future Oncol., 2009, 5, 1065.

[30] Liu X., Zhang Y., Zhu Z., Ha M., Wang Y.: “Elevated pretreatment serum concentration of YKL-40: an independent prognostic biomarker for poor survival in patients with colorectal cancer”. Med. Oncol., 2014, 31, 85.

[31] Tschirdewahn S., Reis H., Niedworok C., Nyirady P., Szendröi A., Schmid K.W., et al.: “Prognostic effect of serum and tissue YKL-40 levels in bladder cancer”. Urol. Oncol., 2014, 32, 663.

[32] Schultz N.A., Christensen I.J., Werner J., Giese N, Jensen BV, Larsen O, et al.: “Diagnostic and prognostic impact of circulating YKL-40, IL-6, and CA 19.9 in patients with pancreatic cancer”. PLoS One, 2013, 8, e67059.

[33] Fan J.T., Li M.J., Shen P., Xu H., Li D.H., Yan H.Q.: “Serum and tissue level of YKL-40 in endometrial cancer”. Eur. Gynecol. Oncol., 2014, 35, 304.

[34] Shao R., Cao Q.J., Arenas R.B., Bigelow C., Bentley B., Yan W. “Breast cancer expression of YKL-40 correlates with tumour grade, poor differentiation, and other cancer markers”. Br. J. Cancer, 2011, 105, 1203.