Abstract 4620: The Secretory Leukocyte Peptidase Inhibitor (SLPI) is differentially expressed in normal ovary and ovarian tumor tissues
Authors: Martin Brennan D. , Adams Melissa D. , Horlick Elizabeth A. , Murphy Patricia G. , Malinowski Douglas P. 
Published: February 2011

Background: The prognosis for epithelial ovarian cancer (EOC) is significantly improved if detected and treated while contained in the ovaries. However, the majority of ovarian cancer cases are diagnosed after the cancer has spread beyond the ovaries. Serum-based biomarker screening offers the potential to significantly increase the detection of cancer at earlier stages and therefore improving patient prognoses. CA125 (MUC16) is a serum biomarker that is elevated in the majority of ovarian cancer cases, but is limited in clinical utility due to low sensitivity for the detection of early stage disease. One potential complementary biomarker is Secretory Leukocyte Peptidase Inhibitor (SLPI).

Objective: In order to assess the potential utility of SLPI as a biomarker for ovarian cancer detection, we have analyzed the expression of both SLPI mRNA and protein in a panel of 27 normal ovary tissue specimens and 61 epithelial ovarian tumors.

Methods: SLPI mRNA expression analysis was performed with RNA isolated from fresh frozen tissue specimens using real-time RT-PCR. Median mRNA expression values for the normal and cancerous specimens were compared using the Mann-Whitney U test. Protein expression levels were characterized by immunoblotting whole cell lysates prepared from the same tissues.

Results: SLPI transcript levels were found to be significantly up-regulated in the ovarian tumor specimens relative to the levels in normal ovary tissues (two-tailed p&lt;0.0001). Eighty-seven percent (53/61) of the tumor specimens exhibited at least a 10-fold increase in SLPI mRNA as compared to the average expression measured in the 27 normal ovarian tissues. SLPI mRNA expression was increased at least 100-fold in 52% of the tumors. Furthermore, SLPI transcript levels differed significantly between normal ovarian tissue and each of the four major histological subtypes of epithelial ovarian cancer: serous (p&lt;0.0001); endometrioid (p&lt;0.0001), clear cell (p&lt;0.0001) and mucinous (p&lt;0.0001). Tumor specimens were compared to normal ovary samples on the same immunoblot, with equivalent loading of total protein. Overall, 82% (50/61) of the tumor specimens exhibited a qualitative increase in SLPI protein expression relative to the levels observed in normal ovarian tissues. Overexpression of SLPI protein was observed in all four major histological subtypes of EOC, with 79.3% (23/29) of serous and 69.2% (9/13) of mucinous samples demonstrating increased SLPI protein expression. One hundred percent of both the endometrioid and clear cell subtypes (9/9 and 8/8, respectively) also stained positive for SLPI protein. Immunoblot results were in concordance with the mRNA expression (cut-off of greater than 10-fold) for 85.2% (52/61) of the samples.

Conclusion: These mRNA and protein expression data support further investigation into the potential effectiveness of SLPI as a biomarker for detection of EOC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4620.