To analyze the expression profile of placental type alkaline phosphatase (PLAP), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in serous ovarian cancer and to correlate their expression with the tumor aggressiveness and progression.
Retrospective study considering a tissue microarray of 82 women affected by ovarian serous cancer. Protein expression was assessed by immunohistochemistry on ovarian serous cancer tissue samples. Immunohistochemical staining was semiquantitatively evaluated as H-score.
Median H-score values were lower for PLAP, 1 (IQR 0-4) than CA125, 10 (IQR 6-12) or HE4, 8 (IQR 5-12). Even if PLAP was less expressed in the cells of serous ovarian cancer than CA125 or HE4 it was relatively more expressed in the fourth quartile of its H-score distribution among cases with low CA125 or HE4 expression. Furthermore, PLAP and HE4 high expression resulted to be significantly correlated with a better prognosis.
PLAP could be an additional marker for early detection of serous ovarian carcinoma, together with the established CA125 and HE4. In addition, PLAP expression is correlated with prognosis, giving, in this way, an additional tool for improving treatment approach.
Agarwal R, , Kaye SB. Prognostic factors in ovarian cancer: how close are we to a complete picture? Ann Oncol 2005; 16: 4-6.
Al-Attar A, , Gossage L, , Fareed KR, et al. Human apurinic/ apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers. Br J Cancer 2010; 102: 704-709.
Bast R, Jr, Klug TL, , St John E, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983; 309: 883-887.
Bast RC Jr. Status of tumor markers in ovarian cancer screening. J Clin Oncol 2003; 21: 200s-205s.
Berek JS, , Bast R Jr. Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection. Cancer 1995; 76: 2092-2096.
Berman ML. Future directions in the surgical management of ovarian cancer. Gynecol Oncol 2003; 90: S33-S39.
Drapkin R, , von Horsten HH, , Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005; 65: 2162-2169.
Fisken J, , Leonard RC, , Shaw G, et al. Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer. J Clin Pathol 1989; 42: 40-45.
Gospodarowicz M, , Wittekind C, , Sobin L, et al. TNM Classification of Malignant Tumours, 7th Edition. Wiley-Blackwell 2009.
Hamilton-Dutoit SJ, , Lou H, , Pallesen G. The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzymes in normal and neoplastic human tissues. An immunohistological survey using monoclonal antibodies. APMIS 1990; 98: 797-811.
Heintz APM, , Odicino F, , Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95(1): S161-S192.
Hung H, , Chiang CT. Estimation methods for time-dependent AUC models with survival data. Canadian Journal of Statistics 2010; 38: 8-26.
Kellen JA, , Bush RS, , Malkin A. Placenta-like alkaline phosphatase in gynecological cancers. Cancer Res 1976; 36: 269-271.
Londero AP, , Orsaria M, , Tell G, et al. Expression and prognostic significance of APE1/Ref-1 and NPM1 proteins in high-grade ovarian serous cancer. Am J Clin Pathol 2014; 141: 404-414.
Malpica A, , Deavers MT, , Lu K, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004; 28: 496-504.
McDicken IW, , McLaughlin PJ, , Tromans PM, et al. Detection of placental-type alkaline phosphatase in ovarian cancer. Br J Cancer 1985; 52: 59-64.
Moore RG, , MacLaughlan S, , Bast RC Jr. Current state of biomarker development for clinical application in epithelial ovarian cancer. Gynecol Oncol 2010; 116: 240-245.
Nakopoulou L, , Stefanaki K, , Janinis J, et al. Immunohistochemical expression of placental alkaline phosphatase and vimentin in epithelial ovarian neoplasms. Acta Oncol 1995; 34: 511-515.
Rosen DG, , Wang L, , Atkinson JN, et al. Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol 2005; 99: 267-277.
Rossi A, , Braghin C, , Soldano F, et al. A proposal for a new scoring system to evaluate pelvic masses: Pelvic Masses Score (PMS). Eur J Obstet Gynecol Reprod Biol 2011; 157: 84-88.
Saini D, , Kala M, , Jain V, et al. Targeting the active site of the placental isozyme of alkaline phosphatase by phage-displayed scFv antibodies selected by a specific uncompetitive inhibitor. BMC Biotechnol 2005; 5: 33.
Steffensen KD, , Waldstr?m M, , Brandslund I, et al. The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients. Int J Gynecol Cancer 2012; 22: 1474-1482.
Stendahl U, , Lindgren A, , Tholander B, et al. Expression of placental alkaline phosphatase in epithelial ovarian tumours. Tumour Biol 1989; 10: 126-132.
Stigbrand T, , Riklund K, , Tholander B, et al. Placental alkaline phosphatase (PLAP)/PLAP-like alkaline phosphatase as tumour marker in relation to CA 125 and TPA for ovarian epithelial tumours. Eur J Gynaecol Oncol 1990; 11: 351-360.
Tholander B, , Taube A, , Lindgren A, et al. Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase in patients with ovarian carcinoma: influence of histological type, grade of differentiation, and clinical stage of disease. Gynecol Oncol 1990; 39: 26-33.
Tonik SE, , Ortmeyer AE, , Shindelman JE, et al. Elevation of serum placental alkaline phosphatase levels in cigarette smokers. Int J Cancer 1983; 31: 51-53.
Trimbos JB, , Parmar M, , Vergote I, et al. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 2003; 95: 105-112.
Wang J, , Gao J, , Yao H, et al. Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis. Tumour Biol 2014; 35: 6127-6138.