IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16INK4a expression

Abstract

Adenocarcinoma in situ of the uterine cervix remains a diagnostic challenge in a small proportion of cases. This suggests a need for biomarker that may be of help in establishing the diagnosis. The aim of this study was to evaluate the potential of insulin-like growth factor-II mRNA-binding protein 3 and cyclin-dependent kinase inhibitor p16 INK4a as biomarkers for adenocarcinoma in situ. Forty-four samples of adenocarcinoma in situ from 40 patients and 23 control cases of benign uterine cervix were included in this study. In addition to benign endocervical epithelium, 19 of these 23 control cases also showed focal tubal metaplasia. Cytoplasmic immunoreactivity for insulin-like growth factor-II mRNA-binding protein 3 was identified in 41 (93%) adenocarcinoma in situ samples, among which, 29 (71%), 10 (24%), and 2 (5%) samples showed insulin-like growth factor-II mRNA-binding protein 3 positive staining in 50% or more, 45 to o50 and o5% of adenocarcinoma in situ lesional cells, respectively. Immunohistochemical reaction intensity for insulin-like growth factor-II mRNA-binding protein 3 was found to be strong in 34 adenocarcinoma in situ samples, intermediate in five, and weak in two. All 23 control cases were negative for insulin-like growth factor-II mRNAbinding protein 3. p16 INK4a expression was identified in all of the adenocarcinoma in situ samples with intermediate staining intensity seen in seven samples and strong in the remainder. Fourteen of 19 (74%) tubal metaplasia cases showed p16 INK4a immunoreactivity in 450% of the tubal metaplastic epithelium with staining intensity ranging from weak to strong. Our findings demonstrate significant expression of insulin-like growth factor-II mRNA-binding protein 3 and p16 INK4a in adenocarcinoma in situ as compared to benign endocervical glands, suggesting that expression of these biomarkers may be helpful in the distinction of adenocarcinoma in situ from benign endocervical glands, particularly in difficult borderline cases.

IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype

“…Although IGF2BP3 is expressed in a variety of malignant neoplasms, including pulmonary small cell, 19 endometrial, 20 and cervical carcinomas, 21 prognostic value has been shown only in renal clear cell carcinomas, 8 other types of renal carcinomas, 22 and low-stage urothelial carcinomas of the bladder. 23 Validation of the association with prognosis in an independent case series has been exclusively reported for renal clear cell carcinoma.…”

“…Microarray hybridization and washing were carried out using standard procedures. 20,21 Microarrays were scanned on a GenePix 4000 microarray scanner and fluorescence ratios (tumor/reference) were calculated using GenePix software. Only spots with a ratio of signal over background of at least 1.5 in the Cy5 and 1.5 in the Cy3 channel were included.…”

Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations

“…A monoclonal antibody specific for IMP3 has been developed and used successfully with routine immunohistochemical methods to study overexpression of the protein in malignant pancreatic, renal, and uterine endocervical lesions. 3,7,8 Expression of IMP3 in endometrial carcinomas has not been previously studied. The aims of this study were to evaluate the expression of IMP3 in endometrial carcinomas especially endometrioid adenocarcinoma and serous carcinoma subtypes as well as benign endometrium using immunohistochemical techniques, to assess the diagnostic utility of IMP3 in distinguishing endometrioid adenocarcinoma from serous carcinoma, to correlate IMP3 expression with clinicopathologic features of the disease, and to understand the possible role of IMP3 in the pathogenesis of endometrial adenocarcinoma.…”

Usefulness of insulin-like growth factor II mRNA-binding protein 3 (IMP3) as a new marker for the diagnosis of esophageal adenocarcinoma in challenging cases

“…Although IMP3 expression is normal in embryonic epithelium, muscle, and placenta of the human fetus, its expression is either minimal or absent in adult human tissues (8,10). This oncofetal protein is highly expressed in various types of human malignant neoplasm, including lung, colon, pancreas, and stomach cancers; soft tissue sarcomas; endometrial serous carcinoma; and endocervical adenocarcinoma; there is, however, no expression in the surrounding benign tissues (9,(11)(12)(13)(14)(15). Few studies have shown that IMP3 is a very useful marker to diagnose low-grade from high-grade Esophageal dysplasia/adenocarcinoma (5,16).…”