IMP3 Expression in Human Ovarian Cancer is Associated With Improved Survival

Abstract

The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68 carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm these findings, we further determined IMP3 mRNA expression in 43 ovarian cancer specimens by real time quantitative reverse transcription-polymerase chain reaction. A significant correlation between protein and mRNA levels (r=0.414, P=0.006), as well as a correlation of IMP3 mRNA expression with patient overall survival (P=0.044), was observed. Our results demonstrate that IMP3 is expressed in a subpopulation of ovarian cancer and a marker of good prognosis.

The use of insulin like-growth factor II messenger RNA binding protein–3 in diagnostic pathology

“…Table 1 outlines the reported frequencies of IMP3 expression in human malignancies, either by immunohistochemistry or reverse transcription polymerase chain reaction (RT-PCR) studies. IMP3 is expressed in a variety of tumors with variable positivity, including pancreatic adenocarcinoma, esophageal adenocarcinoma, melanoma, gallbladder carcinoma, serous endometrial carcinoma, Hodgkin lymphoma, pulmonary and extrapulmonary small cell carcinoma, pulmonary large cell neuroendocrine carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, gastric adenocarcinoma, ovarian carcinoma, non-small cell lung cancer, follicular thyroid carcinoma, laryngeal squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma of the bladder, osteosarcoma, malignant pleural mesothelioma, meningioma, pituitary adenoma, and pituitary carcinoma [6,9,[11][12][13][14][15][16][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][39][40][41][42][43][44][45][46][47][48][49][50][51][52]…”

Insulin-Like Growth Factor-II mRNA-Binding Protein 3 Expression in Effusion Cytology: A Marker for Metastatic Adenocarcinoma Cells and a Potential Prognostic Indicator in Gastric Adenocarcinoma

“…Normal adult tissues do not contain immunohistochemically detectable levels of IMP3, but its expression is significantly upregulated in different human malignancies including adenocarcinomas of various origins [13,14,15,16,17,18,19,20,21,22]. These findings suggest that immunohistochemical analysis of IMP3 expression can be used to differentiate benign processes from malignant processes in different organs and specimens [23,24,25].…”

“…Recent studies have demonstrated IMP3 reactivity in adenocarcinomas from a variety of primary sites [13,14,15,16,17,18,19,20,21,22]. Furthermore, IMP3 has been associated with poor prognosis [15,17,18,19,20,21,22].…”

“…It is expressed in the developing epithelium, muscle and placenta, but it is expressed at low or undetectable concentrations in adult tissues [10,][11]. It exerts profound effects on cellular adhesion and invasion during cancer formation [12] and has been reported to be expressed in different human malignancies, including a variety of adenocarcinomas [13,14,15,16,17,18,19,20,21,22]. Furthermore, several studies have demonstrated that upregulation of IMP3 is associated with tumor metastasis and a more aggressive clinical course, which correlate with poor prognosis [15,17,18,19,20,21,22].…”

IMP3 as a cytoplasmic biomarker for early serous tubal carcinogenesis

“…Kobel et al demonstrated IMP3 expression in 86% of mucinous tumors, in about half of clear-cell and high-grade serous carcinomas, and in 27% of endometrioid cancers [19]. Noske et al detected expression of IMP3 in 32 (47%) of 68 ovarian carcinomas but did not report their findings according to various histologic types [33]. However, no studies have been addressed regarding the IMP3 expression in precursor or early lesions of HGSC of either tubal or "ovarian" origins.…”