Serum sICAM-1 (soluble intercellular adhesion molecule-I) and M-CSF (macrophage colony-stimulating growth factor) throughout monitoring of 34 non-serous ovarian cancers

Purpose: Evaluation of serum ICAM-1 (soluble intercellular adhesion molecule-1) and M-CSF (macrophage colony-stimulating growth factor) determinations for monitoring patients with non-serous ovarian cancers.

Methods: ELISA assay of sICAM-1 (cut-off 235 ng/ml) and M-CSF (cut-off 450 pg/ml) in 190 blood samples from 34 patients.

Results: In pre-treatment sera (n=17), sICAM-1 was over the cut-off in 12/17 (70.6%), M-CSF in 14/17 (82.4%) and CA 125 in 12/16 (75%). sICAM-1 was related only to age at diagnosis (p=0.0008). M-CSF was positively correlated to FIGO stage (p=0.04) CA 125 was elevated in 90.9% of adenocarcinomas (p=0.033 vs other). None of the 3 biological markers were related to other clinico-pathological criteria. Among disease-free patients, higher median concentrations of sICAM-1 and M-CSF were recorded under adjuvant treatment than without (p=0.014, and p=0.08, respectively). After relapse, the highest levels of sICAM-1, M-CSF and CA 125 were observed in progressive disease (46/53, 86.8% (p=0.014), 51/53 96.2% (p=0.008) and 46/52 88.5% (p>0.05), respectively).

Conclusion: In non-serous ovarian cancers, sICAM-1 although elevated in most cases, is not useful for monitoring. Serum M-CSF is a valuable marker when ovarian tumours do not express CA 125.

ICAM-1; M-CSF (CSF-1); Ovarian cancer

[1] Santin A. D.,R ose G. S.,H iserodt J. C.,F ruehaurf J.. Eck L. M., Garcia R. I. et al.: "Effects of cytokines combined with high-dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule-] in human ovarian cancers". Int. J. Cancer, 1996, 65, 688.

[2] Takizawa K., Kamijo R., Ito D.,H atori M., Sumitami K., Nagumo M.: "Synergistic induction of ICAM-1 by cisplatin and 5-fluorouracil in a cancer cell line via a NF-KB independent pathway". Br. J. Cancer, 1999, 80, 954.

[3] Banks R. E., Gearing A. J. H., Hemingway I. K., Norfolk D.R., Peren T. J., Selby P. J.: "Circulating intercellular adhesion molecule-1 (ICAM-1), E-Selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies". Br. J. Cancer, 1993, 68, 122.

[4] Giavazzi R., Nicoletti M. I., Chirivi R. G. S., Hemingway I., Bernasconi S.,A llavena P. et al.: "Soluble intercellular adhesion molecule-I (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts". Eur. J. Cancer, 1994, 3OA, 1865.

[5] Ferdeghini M., Gadducci A., Frontera C., Annichiardo C., Gagetti O., Bianchi M. et al.: "Preoperative serum intercellular adhesion molecule-I (ICAM-1) and E-selectin (endothelial cell leukocyte adhesion molecule ELAM-I) in patients with epithelial ovarian cancer". Anticancer Res., 1995, 15, 2255.

[6] Darai E.. Bringuier A. F., Walker-Combouze F., Feldmann G., Madelena! P., Scoazec J. Y.: "Soluble adhesion molecules in serum and cyst from patients with cystic tumours of the ovary". Human Reprod., 1998, 13, 2831.

[7] Fixe P., Praloran V.: "M-Csf: haematopoietic growth factor or inflammatory cytokine?". Cytokine, 1998, 10, 32.

[8] Kommoss F., Wolfe T., Bauknecht J., Pfisterer M., KiechleSchwartz A. et al.: "Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary". J. Pathol., 1994, 174, 11.

[9] Keshava N., Gubba S., Tekmal R. R.: "Overexpression of macrophage colony-stimulating factor (CSF-1) and its receptor, c-fms, in normal ovarian granulosa cells leads to cell proliferation and tumorigenesis". J. Soc. Gynecol. lnvesting, 1999, 6, 41.

[10] Praloran V., Coupey L., Donnard M., Berrada L., Naud M.F.: "Elevation of serum M-CSF concentrations during pregnancy and ovarian hyperstimulation". Br. J. Haematol., 1994, 86, 675.

[11] Kacinski B. M.,B loodgoodR . S.,S chwartz P. E., Carter D., Stanley E. R.: "Macrophage colony-stimulating factor is produced by human ovarian and endometrial adenocarcinoma-derived cell lines and is present at abnormally high levels in the plasma of ovarian carcinoma patients with acctive disease". Cancer Cells, 1989, 333.

[12] Chambers S., Kacinski B. M., Ivins C. M., Carcangiu M. L.: "Overexpression of epithelial macropahge colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, with a protective epithect of stroma CSF-1". Clin. Cancer Res., 1997, 3, 999.

[13] Kimura F., Takemura Y., Ohtsuki T., Mizukami H., Takagi S., Yamamoto K. et al.: "Serial changes of the serum macrophage colony-stimulating factor level after cytoreductive chemotherapy". Int. J. Hematol., 1992, 55, 147.

[14] Scholl S. M., Bascou C.H., Mosseri V., Olivares R., Magdelenat H., Dorval T. et al.: "Circulating levels of colonystimulating factor 1 as a prognostic indicator in 82 patients with epithelial ovarian cancer". Br. J. Cancer, 1994, 69, 342.

[15] Price F. V., Chambers S. K., Chambers J. T., Carcangiu M L., Schwartz P. E., Kohom E. I. et al.: "Colony-stimulating factor-1 in primary ascites of ovarian cancer is a significant predictor of survival". Am. J. Obstet. Gynecol., 1993, 168, 520.

[16] Kacinski B. M.、Stanley E. R., Carter D., Chambers J. T., Chambers S. K., Kohorn E. I. et al.: "Circulating levels of CSF-1 (M-CSF), a lymphohematopoietic cytokine, may be a useful marker of disease status in patients with malignant ovarian neoplasms". Int. J. Radiation Oncology Biol. Phys., 1989, 17, 159.

[17] Xu F. J.,R amakrishnan S.,D aly L.,S oper J. T., Berchuck A., Clarke-Pearson D. et al.: "Increased serum levels of macrophage colony-stimulating factor in ovarian cancer". Am. J. Obstet. Gynecol., 1991, 165, 1356.

[18] Suzuki M., Ohwada M., Sato I., Nagamoto M.: "Serum levels of macrophage colony-snmulatmg factor as d marker for gynecologic malignancies". Oncology, 1995, 52, 128.

[19] Elg S. A., Yu Y., Carson L. F., Adcock L. L., Twiggs L. B., Prem K. A., Ramakrishnan S.: "Serum levels of macrophage colony-stimulating factor in patients with ovarian cancer undergoing second-look laparotomy". Am. J. Obstet Gynecol., 1992, 166, 134.

[20] Gadducci A., Ferdeghini M., Castellani C., Annicchiarico C., Frontera C., F acchini V. et al.: "Serum macrophage colony-stimulating factor (M-CSF) levels in patients with epithelial ovarian cancer". Gynecol. Oneal., 1998, 70, 111.

[21] Woolas R. P., Xu F. J., Jacobs I. J., Yu Y. H., Daly L., Berchuck A. et al.: "Elevation of multiple serum markers in patients with 、tage I ovarian cancer". J. Natl. Cancer Inst., 1993, 85, 1748.

[22] Woolas R. P., Conaway M. R., Xu F. J., Jacobs I. J., Yu Y.H., Daly L. et al.: "Combinations of multiple serum markers are superior to individual assays for dicrirninating rnalignant from benign pelvic masses". Gynecol. Oncol., 1995, 59, 111.

[23] Rodhe L. E., Hennekens C. H., Ridker P. M.: "Cross-sectional study of soluble intercellular adhesion molecule-I and cardiovascular risk factors in apparently healthy men". Arterioscler. Thromb. Vase. Biol., 1999, 19, 1595.