HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up

Objective: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up.

Methods: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival.

Results: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients.

Conclusion: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Ovarian cancer; Heat shock protein 27; HSP27; Survival

[1] Jemal A., Murray T., Samuels A., Ghafoor A., Ward E., Thun M J.: "Cancer Statistics, 2003". CA Cancer J. Clin., 2003, 53, 5.

[2] Parkin D. M., Pisani P., Feraly J.: "Global cancer statistics". CA Cancer J. Clin., 1999, 49, 33.

[3] Ritossa F. M.: "A new puffing pattern induced by heat shock and DNP in Drosophilia". Experientia, 1962, 18, 571.

[4] Tissieres A., Mitchell H.K., Tracy U. M.: "Protein synthesis in salivary glands of Drosophilia melanogaster: relation to chromosome puffs". J. Mot. Biol., 1974, 84, 389.

[5] Ritossa F. M.: "A new puffing pattern induced by heat shock and DNP in Drosoph山a". Experientia, 1962, 18, 571.

[6] Tissieres A., Mitchell H.K., Tracy U. M.: "Protein synthesis in salivary glands of Drosophilia melanogaster: relation to chromosome puffs". J. Mol. Biol., 1974, 84, 389.

[7] Schlesinger M. J.: "Heat-shock proteins". J. Biol. Chem., 1990, 265, 12111.

[8] Devaja O., King R. J.B., Papadopoulos A., Raju K. S.: "Heatshock protein (HSP27) and its role in female reproductive organs" Eur. J. Gynaecol. Oncol., 1997, 18, 16.

[9] Geisler J. P., Geisler H. E., Tammela J., Wiemann M. C., Zhou Z., Miller G. A., Crabtree W.: "Heat shock protein 27: an independent prognostic indicator of survival in patients with epithelial ovarian carcinoma". Gynecol. Oncol., 1998, 69, 14.

[10] Devaja O., King R. J.B., Papadopoulos A., Raju K. S.: "Heatshock protein (HSP27) and its role in female reproductive organs" Eur. J. Gynaecol. Oncol., 1997, 18, 16.

[11] Ciocca D.R., Stati A. 0., Amprino de Castro M. M.: "Colocalization of estrogen and progesterone receptors with an estrogenregulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue". Breast Cancer Res. Treat., 1990, 16, 243.

[12] McGuire W. L., Dressler L. G., Sledge G. W., Ramzy I., Ciocca D. R.: "An estrogen-regulated protein in normal and malignant endometrium". J. Steroid. Biochem., 1986, 24, 155.

[13] Arrigo A. P.:'Tumor necrosis factor induces the rapid phosphorylation of the mammalian heat-shock protein hsp28". Mot. Cell Biol., 1990, 10, 1276.

[14] Kaur P.. Welch W. J., Saklatvala J.: "Interleukin I and tumor necrosis factor increase phosphorylation of the small heat-shock protein. Effects in trophoblasts, Hep G2 and U937 cells". FEES Lett., 1989, 258, 269.

[15] Ciocca D. R., Adams D. J., Bjercke R. J., Edwards D. P., McGmre W. L.: "Immunohistochemical detection of an estrogen regulated protein by monoclonal antibodies". Cancer Res., 1982, 42, 4256.

[16] Ciocca D.R., Adams D. J., Edwards D. P., Bjercke R. J., McGuire W. L.: "Distribution of an estrogen-induced protein with a molecular weight of 24,000 in normal and malignant human tissues and cells". Cancer Res., 1983, 43, 1204.

[17] F raser D., Pad wick M. L., Whitehead M., Coffer A., King R. J "Presence of an oestradiol receptor-related protein in the skin· changes during the normal menstrual cycle". Br. J. Obstet Gynaecol., 1991, 98, 1277.

[18] King R. J., Finley J. R., Coffer A. I., Millis R.R., Rubens R. D "Characterization and biological relevance of a 29-kDa, oestrogen receptor-related protein". J. Ster. Biochem., 1987, 27, 471.

[19] Tabanelli S., Tang B., Gurpide E.: "In vitro decidualization of human endometrial stromal cells". J. Ster. Biochem. Mot. Biol., 1992, 42, 337.

[20] Cano A., Serra V., Rivera J., Monmeneu R., Marzo C.: "Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause". Ferri/. Steril., 1990, 54, 1058.

[21] Coffer A. L., Lewis K. M., Brockas A. J., King R. J.: "Monoclonal antibodies against a component related to soluble estrogen receptor". Cancer Res., 1985, 45, 3686.

[22] Adams J. D., McGuire W. L.: "Quantitative enzyme-linked immunosorbent assay for the estrogen-regulated M 24,000 protein in human breast tumors: correlation with estrogen and progesterone receptors". Cancer Res., 1985, 45, 2445.

[23] McGuire W. L., Dressler L. G., Sledge G. W., Ramzy I., Ciocca D R.: "An estrogen-regulated protein in normal and malignant endometrium". J. Steroid. Biochem., 1986, 24, 155.

[24] Geisler J. P., Geisler H. E., Tammela J., Wiemann M. C., Zhou Z., Miller G. A., Crabtree W.: "A study of heat shock protein 27 in endometrial carcinoma". Gynecol. Oncol., 1999, 72, 347.

[25] Langdon S. P., Rabiasz G. J., Hirst G. L., King R. J.B., Hawkins R. A., Smith J. F., Miller W. R.: "Expression of the heat shock protein HSP27 in human ovarian cancer". Clin. Cancer Res., 1995, 1, 1603.

[26] Schneider J., Jimenez E., Marenbach K., Marx D., Meden H. "Co-expression of the MDR I gene and HSP27 in human ovarian cancer". Anticancer Res., 1998, 18, 2967.

[27] Germain I., Tetu B., Brisson J., Mondor M., Cherian M. G.: "Markers of chemoresistance in ovarian carcinomas: an immunohistochemical stndy of 86 cases". Int. J. Gynecol. Pathol., 1996, 15, 54.

[28] Langdon S. P., Rabiasz G. J., Hirst G. L., King R. J. B., Hawkins R. A., Smith J. F., Miller W.R.: "Expression of the heat shock protein HSP27 in human ovarian cancer". Clin. Cancer Res., 1995, 1, 1603.

[29] Arts H.J. G., Hollema H., Lemstra W., Willemse P. H. B., de Ynes E. G. E., Kampinga H. H., van der Zee A. G. J.: "Heat-shockprotein- 27 (HSP27) expression in ovarian carcinoma: relation in response to chemotherapy and prognosis". Int. J. Cancer, 1999, 84, 234.

[30] Forsdyke D.R.: "Heat shock proteins as mediators of aggregation implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cells". Cell Stress. Chap., 1999, 4, 205.