Prognostic significance of f ascin expression in endometrioid carcinoma

Purpose of investigation: Actin bundling protein fascin has been previously associated with tumor progression in human cancers. We evaluated whether fascin also plays a role in endometrioid carcinomas.

Methods: Cases of 28 proliferative and hyperplastic endometrium and 43 endometrioid carcinomas were examined by immunohistochemistry using antihuman fascin antibody.

Results: Weak fascin expression in glandular epithelium was observed in 39% of non-neoplastic samples and various degrees of fascin expression were observed in 74% of neoplastic samples. The number of positively stained samples and intensity of epithelial staining were significantly higher in endometrioid carcinoma compared to the non-neoplastic group (p < 0.001). The number of posilively stained samples and total fascin scores of stroma were significantly higher in proliferative and hyperplastic endometrium biopsies compared to the endometrioid carcinoma (p < 0.001). Higher grade endometrioid carcinoma cases had significantly increased total epithelial fascin scores (.042, p < 0.05). There was also a significant difference between tumor grade and patient survival (.040, p <0.05). There was a significant correlation between microvessel count and disease-free survival (r =.412, p = .006). In the proliferative and hyperplastic endometrial biopsies microvessels stained homogeneously in all cases (28/28), but in the endometrioid carcinoma group eight out of 43 cases showed heterogeneous fascin staining of microvessels. The difference was significant (.019, p < 0.05).

Conclusions: Our study supported the dynamic role of actin bundling protein fascin in generating and maintaining endometrial neoplasms. It also showed that in the development of neoplasia, stromal fascin expression decreases but epithelial fascin expression up-regulates.

Endometrium; Endometrioid carcinomas; Fascin; Angiogenesis; Prognosis

[1] Adams J.C., Clelland J.D., Collet G.D.M., Matsumura F., Yamashiro S., Zhang L.: " Cell-matrix adhesions differentially regulate fascin phosphorylation". Mal. Biol. Cell, 1999, 10, 4177

[2] Cohan C.S., Welnhofer E.A., Zhao L., Matsumura F., Yamashiro S.: "Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia". Cell Motil. Cytoskeleton, 2001, 48, 109.

[3] Duh F.M., Latif F., Weng Y. et al.: "cDNA cloning and expression of the human homolog of the sea urchin fascin and Drosophila signed genes which actin-bundling protein". DNA Cell Biol., 1994, 13, 821.

[4] Ishikawa R., Yamashiro S., Kohama K., Matsumura F.:'·Regulation of actin binding and actin bundling activities of fascin by caldesmon coupled with tropomyosin". J. Biol. Chem., 1998, 273, 26991.

[5] Grothey A., Hashizume R., Ji H. et al.: "c-erbB-2/Her-2 upregulates fascin, an actin-bundling protein associated with cell motility, in human breast cancer cell lines". Oncogene, 2000, 19, 4864.

[6] Guvakova M.A., Boettiger D., Adams J.C.: "Induction of fascin spikes in breast cancer cells by activation of the insulin-like growth factor- I receptor". Int. J. Biochem. Cell Biol., 2002, 34, 685.

[7] Hu W., McCrea P.D., Deavers M., Kavanagh J.J., Kudelka A.P., Verschraegen C.F.: "Increased expre对on of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors". Clin. Exp. Metastasis, 2000, 18, 83.

[8] Maitra A., Iacobuzio-Donahue C., Rahman A. et al.: "Tmmunohistochemical validation of a novel epithelial and a novel stroma marker of pancreatic ductal adenocarcinoma identified by global express microarrays: sea urchin fascin homolog and heat shock protein 47". Am. J. Clin. Pat ho/., 2002, 118, 52.

[9] Pelosi G., Pa、torino U., Pasini F. et al.: "Independent prognostic value of fascin immunoreactivity in Stage I non small cell lung cancer". Br. J. Cancer, 2003, 88, 537.

[10] Pelosi G., Barisella M., Pasini F. et al.: "CD 117 immunoreactivity in Sage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients". Mod. Pathol., 2004. 17, 711.

[11] Pelosi G., P心ini F., Sonzogni A. et al.: "Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I non small cell lung carcinoma". Cancer, 2003, 97, 2487.

[12] Kempf W., Levi E., Kamarashev J. et al.: "Fascin expression in CD30-positive cutaneous lymphoproliferative disorders·. J. Cutan. Pathol., 2002, 29, 295.

[13] Goncharuk V.N., Ross J.S., Carlson J.A.: "Actin-binding protem fascin expression in skin neoplazi". J. Cutan. Pathol., 2002, 29, 430.

[14] Mutch D.G. Uterine cancer. In: Scott J.R.. Gibbs R.S., Karlan B.Y., Haney A.F. (ed,.), Danforth's Obstetrics and Gynecology, Philadelphia: Lippincott Williams &Wilkins, 2003, 951.

[15] Yen S.S.C.: "Neuroendocrinology and reproduction". In: Straus J.F. Ill, Barbieri R.L. (eds.), Yen and Jaffe's Reproductive Endocrinology. Philadelphia: Elsevier Saunders, 2004, 3.

[16] Silverberg S.G., Sasano N.. Yajima A.: "Endometrial carcinoma in Miyagi Prefecture, Japan: histopathologic analysis of a caner registry-based series and comparison with samples in American women·. Cancer, 1982, 49, 1504.

[17] Dundar E., Tel N., Ozalp S.S., Tsiksoy S., Kabukcuoglu S., Bal C ''The significance of local cellular immune response of women 50 years of age and younger with endometrial carcinoma". Eur. J. Gynaecol. Oneal., 2002, 23, 243.

[18] Puius YA., Mahoney N.M., Almo S.C.: "The modular structure of actin regulatory proteins". Curr. Opin. Cell Biol., 1998, 10. 23

[19] Schlosshauer P.W., Ellenson L.H., Soslow R.A.:β－catenin and Ecadherin expression patterns in high grade endometrial carcinoma are associated with histological subtype". Mod. Pathol., 2002, 75, 1032.

[20] Palacios J., Catasus L., Moreno-Bueno G.M., Matias-Guiu X., Prat J., Gamallo C.: "β-and y-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability". Virchows Arch., 200 I, 438, 464.

[21] Moreno-Bueno G.. Gamallo C., Perez-Gallego L., de Mora J.C., Suarez A., Palacios J.:β－catenin expression pattern, y-catenin gene mutations and microsatellite instability in endometrioid ovarian carcinomas and synchronous endometrial carcinomas''. Diag. Mol. Pathol., 2001, 10, 116.

[22] Jawhari A.U.. Buda A.. Jenkins M. et al.: "Fascin. an actin bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro". Am. J. Path., 2003, 162. 69.

[23] Wong V., Ching D., McCrea P.D., Firestone G.L.: "Glucocorticoid down-regulation of fascin protein expression is required for steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells". J. Biol. Chem., 1999, 274, 5443

[24] Guan Y., Woo P.L.. Rubenstein N.M.. Firestone G.L.:'Transforming growth factor-a abrogates the glucocorticoid stimulation of tight junction formation and reverses the steroid-induced downregulation of fascin in rat mammary epithelial tumor cells by a Ras-depentent pathway''. Exp. Cell Res., 2002. 273, 1.

[25] Shonukan O.T., Bagayogo I., McCrea P.D., Chao M., Hempstead B.: "Neurotropin-induced melanoma cell migration is mediated through actin-bundling protein fascin". Oncogene, 2003, 22, 3616.

[26] Miiller M., Kramer P.H.: "Integrated cell function: apoptosis". In Arias T.M., Boyer J.L., Chisari F.V., Fausto N., Schachter D ..Shafritz D. (eds.). The Liver Biology and Pathobiology, Philadelphia: Lippincott Williams & Wilkins, 200 I, 187.

[27] Wagatsuma S.. Konno R., Sato S., Yajima A.: Tumor ang1ogenesis, hepatocyte growth factor, and c-Met Expression in endomerial carcinoma. Cancer, 1998, 82, 520.

[28] Ozalp S., Yalcin O.T., Acikalin M., Tanir H.M., Oner U., Akkoyunlu A.: "Microvessel density (MVD) as a prognosticator in endometrial carcinoma". Eur. J. Gynaecol. Oncol., 2003, 24, 305.