Immunoradiometric and Immunohistochemical Analysis of Cathepsin D in Ovarian Cancer: Lack of Association with Clinical Outcome

Overview

Journal Br J Cancer

Specialty Oncology

Date 1998 Dec 23

PMID 9862578

Citations 3

Authors

G Ferrandina

G Scambia

A Fagotti

G DAgostino

P Benedetti Panici

A Carbone

S Mancuso

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to analyse the clinical significance of Cathepsin D (Cath D) content as determined by an immunoradiometric assay in a series of primary untreated ovarian cancers from 162 patients. In addition, immunohistochemical analysis of Cath D was also performed on a subset of 86 tumours. Cath D levels were distributed in an asymmetrical way and were skewed towards the lower values (median value 20.8 pmol mg(-1) protein, range 2.0-99.0 pmol mg(-1) protein). No correlation was found between Cath D levels and clinicopathological parameters. However, the percentage of Cath D positivity was significantly higher in oestrogen receptor-positive (57%) compared with oestrogen receptor-negative (36%) cases (P= 0.01). The percentage of Cath D-positive staining was not significantly different for both epithelial (27%) and stromal components (40%). Immunoradiometrically detected Cath D levels were not different according to Cath D stromal immunostaining (P= 0.18), while higher Cath D levels were measured in Cath D-positive than in Cath D-negative tumour epithelial cells (P = 0.027). Survival analysis was conducted on 161 primary untreated ovarian cancer patients. The 5-year overall survival rate was 57% and 55% in Cath D-positive and Cath D-negative patients respectively (P = 0.69). As far as time to progression was concerned, there was no significant difference in the survival rate of patients with either high or low Cath D content (P = 0.56). Similar results have been obtained in the subset of patients in which Cath D was analysed by immunohistochemistry. In conclusion, Cath D measurement in tumour extracts appears to have a limited usefulness in improving the prognostic characterization of ovarian cancer patients.

Citing Articles

The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer.

Pranjol M, Gutowski N, Hannemann M, Whatmore J Biomolecules. 2015; 5(4):3260-79.

PMID: 26610586 PMC: 4693277. DOI: 10.3390/biom5043260.

The role of the tumor stroma in ovarian cancer.

Davidson B, Trope C, Reich R Front Oncol. 2014; 4:104.

PMID: 24860785 PMC: 4026708. DOI: 10.3389/fonc.2014.00104.

Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications.

Leto G, Tumminello F, Crescimanno M, Flandina C, Gebbia N Clin Exp Metastasis. 2004; 21(2):91-106.

PMID: 15168727 DOI: 10.1023/b:clin.0000024740.44602.b7.

References

Mantel N . Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966; 50(3):163-70. View

Ferrandina G, Scambia G, Bardelli F, Benedetti Panici P, Mancuso S, Messori A . Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br J Cancer. 1997; 76(5):661-6. PMC: 2228021. DOI: 10.1038/bjc.1997.442. View

Hsu S, RAINE L, FANGER H . Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981; 29(4):577-80. DOI: 10.1177/29.4.6166661. View

Imort M, Zuhlsdorf M, Feige U, Hasilik A, von Figura K . Biosynthesis and transport of lysosomal enzymes in human monocytes and macrophages. Effects of ammonium chloride, zymosan and tunicamycin. Biochem J. 1983; 214(3):671-8. PMC: 1152302. DOI: 10.1042/bj2140671. View

Vignon F, Capony F, Chambon M, Freiss G, Garcia M, ROCHEFORT H . Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein. Endocrinology. 1986; 118(4):1537-45. DOI: 10.1210/endo-118-4-1537. View

ROCHEFORT H, Capony F, Garcia M, Cavailles V, Freiss G, Chambon M . Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis?. J Cell Biochem. 1987; 35(1):17-29. DOI: 10.1002/jcb.240350103. View

Johnson M, Westley B, May F . Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells. Br J Cancer. 1989; 59(5):727-38. PMC: 2247210. DOI: 10.1038/bjc.1989.153. View

Spyratos F, Maudelonde T, Brouillet J, Brunet M, Defrenne A, Andrieu C . Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet. 1989; 2(8672):1115-8. DOI: 10.1016/s0140-6736(89)91487-6. View

Garcia M, Derocq D, Pujol P, ROCHEFORT H . Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency. Oncogene. 1990; 5(12):1809-14. View

10.

Scambia G, Benedetti P, Ferrandina G, Battaglia F, Baiocchi G, Mancuso S . Cathepsin D assay in ovarian cancer: correlation with pathological features and receptors for oestrogen, progesterone and epidermal growth factor. Br J Cancer. 1991; 64(1):182-4. PMC: 1977323. DOI: 10.1038/bjc.1991.266. View

11.

Altman D . Categorising continuous variables. Br J Cancer. 1991; 64(5):975. PMC: 1977443. DOI: 10.1038/bjc.1991.441. View

12.

Capony F, Maudelonde T, ROCHEFORT H . Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. J Clin Endocrinol Metab. 1992; 75(6):1497-502. DOI: 10.1210/jcem.75.6.1464654. View

13.

Isola J, Weitz S, Visakorpi T, Holli K, Shea R, Khabbaz N . Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer. J Clin Oncol. 1993; 11(1):36-43. DOI: 10.1200/JCO.1993.11.1.36. View

14.

Chalbos D, Philips A, Galtier F, ROCHEFORT H . Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells. Endocrinology. 1993; 133(2):571-6. DOI: 10.1210/endo.133.2.8344199. View

15.

Henzen-Logmans S, Fieret E, Berns E, van der Burg M, Klijn J, Foekens J . Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D. Int J Cancer. 1994; 57(4):468-72. DOI: 10.1002/ijc.2910570405. View

16.

Simon R, Altman D . Statistical aspects of prognostic factor studies in oncology. Br J Cancer. 1994; 69(6):979-85. PMC: 1969431. DOI: 10.1038/bjc.1994.192. View

17.

Eng Tan P, Benz C, Dollbaum C, Moore 2nd D, Edgerton S, Zava D . Prognostic value of Cathepsin D expression in breast cancer: immunohistochemical assessment and correlation with radiometric assay. Ann Oncol. 1994; 5(4):329-36. DOI: 10.1093/oxfordjournals.annonc.a058836. View

18.

Roger P, Montcourrier P, Maudelonde T, Brouillet J, Pages A, Laffargue F . Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages: correlation with cytosolic assay. Hum Pathol. 1994; 25(9):863-71. DOI: 10.1016/0046-8177(94)90004-3. View

19.

Scambia G, Panici P, Ferrandina G, Salerno G, DAgostino G, DiStefano M . Clinical significance of cathepsin D in primary ovarian cancer. Eur J Cancer. 1994; 30A(7):935-40. DOI: 10.1016/0959-8049(94)90118-x. View

20.

Kuhn W, Pache L, Schmalfeldt B, Dettmar P, Schmitt M, Janicke F . Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy. Gynecol Oncol. 1994; 55(3 Pt 1):401-9. DOI: 10.1006/gyno.1994.1313. View