IMP3 can predict aggressive behaviour of lung adenocarcinoma

Diagnostic Pathology

Mari Peric⁴  Violeta Soljic³  Antonia Pavlovic⁵  Veljka Ivcevic²  Vesna Capkun¹  Merica Glavina Durdov⁵  Renata Beljan Perak⁵ 

[1] Department for nuclear medicine, Clinical Hospital Center Split, Split, Croatia;Pulmology Department Clinical Hospital Center Split, Split, Croatia;Institute for pathology, forensic medicine and cytology, University Hospital Mostar, Mostar, Bosnia and Herzegovina;Institute for radiology Clinical Hospital Center Split, Split, Croatia;Institute for pathology, forensic medicine and cytology Clinical Hospital Center Split, Split, Croatia

关键词: IMP-3;    Napsin A;    TTF-1;    Aggressive phenotype;    Lung adenocarcinoma;   

Others  :  807815
DOI  :  10.1186/1746-1596-7-165

 received in 2012-08-28, accepted in 2012-11-25,  发布年份 2012

【 摘 要 】

Background

Lung cancer most often presents as an inoperable tumour and the diagnosis is usually performed on a small biopsy/cytology specimen. In the group of non small cell lung cancer - not otherwise specified, adenocarcinoma phenotype can be determined immunohistochemically using TTF-1 and Napsin A. Expression of oncofetal protein IMP3 in human cancer is associated with poor differentiation and aggressive behaviour. In the present study expression of IMP3 was correlated with expression of TTF-1 and Napsin A, histological subtype and clinical stage of lung adenocarcinoma. We were interested whether distant metastases are associated with IMP3 overexpression, regardless of the histologic subtype of adenocarcinoma.

Methods

In retrospective study, consecutive series of 105 patients with advanced lung adenocarcinoma diagnosed from 2006 to 2009 in Clinical Hospital Center Split, Croatia, were analysed. Clinical data were collected from the Pulmology Department and time of death from the Mortality Registry. Paraffin blocks of bronchoscopic biopsies were collected from the Institute of Pathology and 15 cases excluded from the analysis due to insufficient material. Expression of IMP3, Napsin A and TTF-1 were analysed by indirect enzyme immunohistochemistry. Statistical analysis was performed and P values less than 0.05 considered significant.

Results

Of 90 patients, 71 (78%) were males and 19 (22%) females. Median age for males was 61.5 years (min-max 43–83) and for females 61 years (min-max 44–86). Pleural effusion was found in 15 (16.6%) and distant metastases in 45 (50%) cases. According to histological subtypes, there were 34 acinar, 2 lepidic, 2 papillary and 52 solid subtypes. IMP3 overexpression was found in 63 cases (70%) and was correlated with solid subtype (P = 0.002) and negative/weak Napsin A expression (P = 0.004). Strong Napsin A expression correlated with TTF-1 expression (P = 0.003) and lower histological grades (P = 0.031). Patients with IMP3 overexpression more often had distant metastases than patients with negative IMP3, 55.5% versus 33.3% (P = 0.033). Non solid subtypes with IMP3 overexpression developed distant metastasis more common than non solid subtypes with negative IMP3, 72% versus 35% (P = 0.028).

Conclusions

Expression of IMP3 correlates with solid subtype and with distant metastases regardless of histological subtype of lung adenocarcinoma.

Virtual slides

http://www.diagnosticpathology.diagnomx.eu/vs/1966211581795258 webcite

Zusammenfassung

Hintergrund

Das Lungenkarzinom kommt meistens als nicht resektabler Tumor vor und die Diagnose kann nur in kleinen Biopsaten oder zytologisch gestellt werden. In der Gruppe der nicht kleinzelligen Lungenkarzinome kann der nicht anders spezifizierte Adenokarzinom Phänotyp mit Hilfe der Antikörper TTF-1 und Napsin A diagnostiziert werden. Die Expression des onkoföetalen Proteins IMP3 ist bei humanen Karzinomen mit agressivem Verhalten und metastatischem Potential verbunden. In dieser Studie korreliert die Expression von IMP3 mit TTF-1, Napsin A, histologischem Typ und klinischem Staging des Lungenkarzinoms. Wir waren daran interessiert, ob Fernmetastasen mit IMP3 Überexpression assoziiert sind, unabhängig von der histologischen Subtyp von Adenokarzinom.

Methode

In der retrospektiven Studie wurden die von 2006 bis 2009 im Klinischem Krankenhaus Split, Kroatien diagnostizerte Adenokarzinome der Lunge von 105 Patienten analysiert. Die klinischen Daten stammten aus der Abteilung für Pulmologie und im Falle des Todes vom Todesregister. Die Paraffinblöcke der primären Lungenbiopsate dieser Patienten wurden im Institut für Pathologie mit der indirekter Enzym - Immunohistochemie mittels Kombination der Antikörper gegen IMP3, Napsin A und TTF1 untersucht. 15 Fälle aus der Analyse aufgrund unzureichender Material ausgeschlossen. Es wurde eine statistische Untersuchung durchgeführt und Werte weniger als 0.05 P wurden als statistisch signifikant bezeichnet.

Ergebnisse

Von 90 Patienten mit Lungencarcinom waren 71 (78%) mänlich, durchschnittliches Alter war für Männer 61.5 Jahre (min-max 43–83) und 61 Jahre für Frauen (min-max 44–86). Pleurale Effusionen fand man in 15 Fällen (16.6%) und Fernmetastasen in 45 (50%) Fällen. Histologische Sybtypen waren: 2 lepidic Karzinome, 34 azinäre Karzinome, 2 papilläre und 52 solide Karzinome. IMP3 war exprimiert in 63 Fälle (70%). Positive IMP3 Expression war mit solidem Typ (P = 0.002) und negativer Napsin A Expression (P = 0.004) assoziert. Napsin A Expression war mit niedrigem Gradus (P = 0.031) und positiver TTF-1 Expression (P = 0.003) assoziert. Patienten mit IMP3 Überexpression öfter hatten Fernmetastasen als Patienten mit negativen IMP3, 55.5% versus 33.3% (P = 0.033). Non solide Subtyp mit IMP3 Überexpression entwickelten Fernmetastasen Meer häufiger als nicht festem Subtyp mit negativen IMP3, 72% versus 35% (P = 0.028).

Schlussworte

Die Expression von IMP3 ist mit negaativer Expression von Napsin A, solidem Subtyp und Metastasen verbunden und hat praktische predictive Werte in der pathologischen Diagnose des Adenokarzinoms der Lunge. Die Expression von IMP3 korreliert mit soliden Subtyp und mit Fernmetastasen unabhängig von histologische Subtyp Lungenadenokarzinom.

【 授权许可】

   
2012 Beljan Perak et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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