Oncofetal Protein IMP3, a New Diagnostic Biomarker to Distinguish Malignant Mesothelioma From Reactive Mesothelial Proliferation

Department of Pathology, University of Massachusetts Medical Center, One Innovation Drive, Worcester, MA 01605, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 06/2011; 35(6):878-82. DOI: 10.1097/PAS.0b013e318218985b
Source: PubMed


The distinction of malignant mesothelioma from reactive mesothelial proliferation remains to be a major challenge for surgical pathologists. In this study, we investigated whether insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), an oncofetal protein, can be used as a biomarker to distinguish between malignant and reactive mesothelial cells. A total of 109 cases (mesothelioma, n=45; reactive mesothelial proliferation, n=64) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic staining in 33 of 45 (73%) mesothelioma cases. In contrast, the expression of IMP3 was undetectable in all (64 cases) benign reactive mesothelial proliferations. Among the IMP3-positive mesotheliomas, 27 (82%) exhibited diffuse IMP3 expression. The vast majority of IMP3-positive subtypes of mesotheliomas showed IMP3 expression in >50% of malignant cells, as this diffuse staining pattern occurred in 17 (81%) cases of epithelial, 4 (100%) cases of sarcomatoid, and 6 (75%) cases of mixed types of mesothelioma. In addition, 2 cases, which were initially diagnosed as atypical mesothelial proliferations and later confirmed to be mesotheliomas, showed diffuse IMP3 expression. Our findings suggest that IMP3 is a new positive biomarker for malignant mesothelioma. IMP3 immunohistochemical staining can be used as an adjunct tool in the distinction of malignant mesothelioma from reactive mesothelial proliferations.

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    • "In several studies, it has been demonstrated that IMP3 immunohistochemistry can be employed to differentiate between benign and IMP3 expression in lesions of the gastric mucosa 2098 Int J Clin Exp Pathol 2014;7(5):2091-2101 malignant lesions in the skin [6] [7], the uterine cervix [8] [9], the pancreas [8] [9] [10] [11] and the mesothelium [12] [13]. "
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    ABSTRACT: Aim: Expression of the oncofetal protein insulin like growth factor II messenger ribonucleic acid binding protein 3 (IMP3) has been shown to differentiate between benign and malignant lesions in several tissues. Our aim was to assess the immunohistochemical expression of IMP3 in inflammatory and neoplastic lesions of the gastric mucosa and to determine whether IMP3, alone or in combination with p53, could be used for identifying neoplasia of the gastric mucosa. Methods: IMP3 and p53 immunohistochemistry was performed on 57 cases of gastritis, 28 cases of dysplasia of the gastric mucosa and 63 cases of gastric carcinomas. Focal IMP3 positivity was detected in 86% of non-neoplastic lesions of the gastric mucosa. Using a simple product score (PS), 96% of non-neoplastic lesions of the gastric mucosa were assessed as IMP3(PS) negative. None of the low-grade dysplasia but 83% of high-grade dysplasia were IMP3(PS) positive. Gastric carcinomas showed IMP3(PS) positivity in 65%. Adding p53 to the diagnostic panel increased sensitivity significantly. Conclusion: High-grade dysplasia and gastric carcinomas can be distinguished from low-grade dysplasia and inflammatory lesions of the gastric mucosa with a high specificity and good sensitivity using a combination of the immunohistochemical markers IMP3 and p53.
    International journal of clinical and experimental pathology 05/2014; 7(5):2091-101. · 1.89 Impact Factor
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    ABSTRACT: Benign and malignant pleural processes display a large and overlapping spectrum of morphological appearances, and can be difficult to distinguish, histologically, from each other. β-catenin, a participant in the wingless-type (Wnt) transduction pathway, is involved in the pathogenesis of malignant mesothelioma and has received limited evaluation for its ability to serve as a diagnostic aid for distinguishing between individual pleural disorders. We performed immunohistochemistry for β-catenin on 10 pleural malignant mesotheliomas, 10 examples of mesothelial hyperplasia and 18 cases of organizing pleuritis. Although differences were noted in staining intensity between the mesothelioma and mesothelial hyperplasia groups, extensiveness and cellular location were similar. Staining intensity (mean +/- s.d.) in mesotheliomas (2.00 +/- 0.67) was significantly less intense than in mesothelial hyperplasia cases (3.00 +/- 0.00) (p=0.0005). Stromal cell staining was cytoplasmic in all cases, and endothelial cell staining was membranous, submembranous and cytoplasmic. Nuclear expression of β-catenin was not observed in any of the cases studied. This lack of nuclear staining in the stromal cells of organizing pleuritis differs markedly from the previously reported high frequencies of nuclear β-catenin expression in other pleural spindle cell proliferations (desmoid tumors and solitary fibrous tumors). In summary, the current study adds to previous work indicating a role for β-catenin in the genesis of pleural conditions including organizing pleuritis, mesothelial hyperplasia and malignant mesothelioma. Although IHC for β-catenin does not appear to be conclusive for separating benign from malignant mesothelial proliferations, it may be valuable for assisting in the differential diagnosis of mesothelial and spindle cell proliferations in the pleura.
    International journal of clinical and experimental pathology 01/2011; 4(8):742-7. · 1.89 Impact Factor
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    ABSTRACT: Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes were losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridisation (FISH) analysis in MM has been reported recently, alterations of other genes have not been examined to any great extent. This study analysed the frequency of various genomic gains and losses in MM using FISH analysis. The authors performed a FISH analysis using paraffin-embedded tissues from 42 cases of MM. Chromosomal losses in MM were found at 9p21 (83%), 1p36 (43%), 14q32 (43%) and 22q12 (38%), whereas gains were found at 5p15 (48%), 7p12 (38%) and 8q24 (45%). There were no cases of adenomatoid tumour, benign mesothelial multicystic tumour, reactive mesothelial hyperplasia or pleuritis showing any gains or losses. At least one genomic abnormality was identified in all cases of MM. Among various histological subtypes, the chromosomal abnormality tended to be more common in cases showing sarcomatous elements (biphasic or pure sarcomatoid) than in cases showing an epithelioid histology. The authors found various genomic gains and losses in MM by FISH analysis. The frequency of each genomic gain or loss examined in MM by FISH analysis almost agreed with the comparative genomic hybridisation technique in previous studies. This study suggests that genomic evaluation by FISH analysis might be helpful in distinguishing MM from benign mesothelial proliferation.
    Journal of clinical pathology 11/2011; 65(1):77-82. DOI:10.1136/jclinpath-2011-200208 · 2.92 Impact Factor
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