IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas

Riener, Marc‐Oliver; Fritzsche, Florian; Clavien, Pierre‐Alain; Paulweber, Bernhard; Probst‐Hensch, Nicole; Jochum, Wolfram; Kristiansen, Glen

doi:10.1016/j.humpath.2009.01.024

Cited by 64 publications

(81 citation statements)

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“…IMP3 is considered an oncofetal protein that is expressed in fetal and carcinogenic tissue; however, the exact function of IMP3 remains unknown (7)(8)(9)(10)(11)(12). Expression of IMP3 has been studied in a wide variety of cancers, including renal cell carcinoma (13,14), adenocarcinoma of the uterine cervix (15), endometrial carcinoma (16), adenocarcinoma of the esophagus (17), malignant melanoma (18), Merkel cell carcinoma (19), urothelial carcinoma (20), neuroendocrine carcinoma of the lung (21), gastric adenocarcinoma (22), hepatocellular carcinoma (23), pancreatic (24)(25)(26)(27) and biliary tract (27) adenocarcinoma, and triple negative breast cancer (28), where this marker has frequently been associated with enhanced tumor aggressiveness and a worse outcome.…”

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confidence: 99%

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

et al. 2017

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Abstract. Expression of p16 has been established as a good surrogate marker for high-risk human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) patients, and it has been associated with an improved prognosis, irrespective of the actual HPV status. Conversely, the human insulin-like growth factor II mRNA binding protein 3 (IMP3) has been related to aggressiveness in several types of tumors. The aim of the present study was to investigate and compare p16 and IMP3 as markers of favorable and unfavorable behavior, respectively, in head and neck SCC (HNSCC), with particular reference to the HPV status. Both markers were analyzed by immunohistochemical analysis of 156 HNSCC samples originating from the oropharynx (n=81), oral cavity (n=44), larynx (n=15), hypopharynx (n=10) and nasopharynx (n=6). The HPV status was examined in a randomly selected representative subcohort (n=38) using polymerase chain reaction. Of the 156 HNSCC samples, 81 (51.9%) and 54 (34.6%) were positive for IMP3 and p16, respectively. IMP3 expression (P=0.022), p16 expression (P<0.001) and the combination of these markers (P<0.001) were significantly associated with tumor site. In particular, 69/81 (85%) OPSCC samples were positive for either one or both markers compared with 36/75 (48%) SCC samples from other sites. p16 expression was significantly associated with HPV infection (P= 0.017) and a trend towards a negative association between IMP3 expression and HPV infection was observed (P=0.053). The results of the present study suggested that IMP3 and p16 are more frequently expressed in OPSCC compared with other HNSCCs. The prognostic impact of IMP3 on OPSCC remains to be investigated in a larger series with an extended follow-up period. IntroductionSquamous cell carcinoma (SCC) is the leading cancer type affecting the head and neck region (HNSCC) representing >90% of malignant neoplasms of the oral cavity and oropharynx and 5 and 2% of all cancers in men and women, respectively (1). Tobacco smoking and alcohol consumption are the two major etiological factors of HNSCC and they work in a synergistic manner to initiate SCC (1). Approximately 75% of HNSCC cases in western countries are related to these two major risk factors, while the remainder is predominantly associated with viral infection, in particular infection with high-risk human papillomavirus (HPV) (1). HPV has been detected in a small fraction of oral cavity SCCs, and in 40-50% of oropharyngeal (mainly tonsillar) SCC (OPSCC) (1). While HPV-associated HNSCC may occur at any site, including the sinonasal tract, the majority of HPV-related SCCs originate in the lymphoid tissue bearing the oropharynx, mainly the palatine tonsil and the base of the tongue (1). Expression of p16 as a consequence of oncogenic HPV infection has been increasingly used as a surrogate marker for high-risk HPV infection, particularly in the female genital tract and the oropharynx (2,3). The sensitivity and specificity of p16 immunostaining for detecting high-risk HPV in OPSCC patie...

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confidence: 99%

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

et al. 2017

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Lee

et al. 2014

Acta Cytologica

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Objective: The aim of our study was to identify the diagnostic value of insulin-like growth factor-II mRNA-binding protein 3 (IMP3) in distinguishing metastatic adenocarcinoma cells (MAC) from reactive mesothelial cells (RMC) in effusions. We also investigated the role of IMP3 as a prognostic indicator for patients with malignant effusion. Study Design: A total of 156 cell block specimens, including 116 malignant effusions with MAC and 40 benign effusions with RMC, were subjected to immunocytochemical staining for IMP3. Results: Immunocytochemical studies showed positive staining for IMP3 in 91 of 116 (78.4%) cases of MAC and in 3 of 40 (7.5%) cases of RMC. With regard to distinguishing MAC from RMC, the IMP3 reactivity was found to be 78.4% sensitive and 92.5% specific with a positive predictive value of 96.8% and a negative predictive value of 59.7%. Diffuse IMP3 expression (>25%) in MAC from patients with gastric adenocarcinoma was associated with shorter survival (p = 0.001). Conclusion: Our data suggest that IMP3 is a helpful marker for differentiating MAC from RMC, and that diffuse IMP3 expression is a poor prognostic indicator in patients with gastric adenocarcinoma and malignant effusion.

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“…Cytoplasmic positivity has been demonstrated in 71% to 97% of pancreatic ductal adenocarcinomas in various studies including cytology specimens, 162,167,[172][173][174][175][176][177] 82% of gallbladder adenocarcinomas, 168,178 and 50% to 92% of a d enoca rcino ma s o f ex tr a hep a tic b ile ducts. 169,170,[178][179][180] Intrahepatic cholangiocarcinomas also overexpress IMP3 at a high frequency (82%-90%), 167,181 but lower frequencies (37%-41%) are also reported. 178,182 In our experience, the greatest advantage of IMP3 is its high specificity for malignancy (Figure 11, B).…”

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“…169,170,[178][179][180] Intrahepatic cholangiocarcinomas also overexpress IMP3 at a high frequency (82%-90%), 167,181 but lower frequencies (37%-41%) are also reported. 178,182 In our experience, the greatest advantage of IMP3 is its high specificity for malignancy (Figure 11, B). Nonneoplastic pancreaticobiliary epithelial cells are always negative.…”

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“…Nonneoplastic pancreaticobiliary epithelial cells are always negative. However, IMP3 does not discriminate invasive adenocarcinoma from dysplasia, 169,171,178 and thus careful histologic evaluation is still essential. Another disadvantage is that approximately 50% of malignant cases show only focal positivity, which significantly reduces its sensitivity because there may be only rare malignant cells present in a given biopsy.…”

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Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

Wang¹,

Kim²,

Koo³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Objectives.— To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. Data Sources.— Data sources include literature review, authors' research data, and personal practice experience. Conclusions.— Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.

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IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas

Cited by 64 publications

References 29 publications

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

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

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

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