Exspression of tyrosine kinase receptors of epidermal growth factor in sporadic cardiac myxoma

Obitelj tirozin kinaznih receptora epidermalnog čimbenika rasta čine četiri člana: EGFR1/c-erbB1, c-erbB2, c-erbB3 i c-erbB4. Oni su uključeni u proliferaciju, diferencijaciju i preživljenja tumorskih stanica, te angiogeneze. Kada su ko-eksprimirani njihova heterodimerizacija pospješuje patološku signalizaciju epidermalnih čimbenika rasta. U ovoj studiji analizirana je proteinska i mRNA ekspresija ovih tirozin kinaznih receptora i njihova stanična lokalizacija u sporadičnom miksomima srca. Studijom je obuhvaćeno 36 pacijenata. Ekspresija EGFR1/c-erbB1, c-erbB2, c-erbB3 i c-erbB4 analizirana je imunohistokemijskim i qRT-PCR pristupom. Populacija pacijenata obuhvaćala je 27 (75%) žena i 9 (25%) muškaraca. Srednja dob pacijenata iznosila je 63 godine, s rasponom od 34 do 87 godina života. Svi uzorci tumorskog tkiva kirurški su odstranjeni iz lijevog atrija. Većina ispitanih uzoraka tumorskog tkiva pokazuje umjerenu do jaku i preklapajuću ekspresiju tirozin kinaznih receptora, osim c-erbB2 koji se pokazao imunološki negativnim (HercepTestTM) u svim slučajevima. Ekspresija c-erbB4 mRNA statistički je značajno smanjena u tumorskom tkivu u odnosu na normalno tkivo lijevog atrija. Korelacijska analiza tirozin kinaznih receptora pokazala je da samo c-erbB2 i c-erbB3 pokazuju statistički značajnu (p= 0,01304) i pozitivnu (r= 0,721) korelaciju. Može se zaključiti da su EGFR1/c-erbB1, c-erbB2 (samo mRNA razina), c-erbB3 i c-erbB4 ko-eksprimirani u sporadičnom miksoimima srca i mogu igrati potencijalno značajnu ulogu u njihovoj histopatogenezi.The epidermal growth factor receptor family (EGFR) consist of four tyrosine kinas receptors, EGFR1/c-erbB1, c-erbB2, c-erbB3 and c-erbB4. They are involved in tumor cell proliferation, differentiation, survival and angiogenesis. Co-expressed in the same neoplastic cell source with accompanying hetero-dimerization they further enhance pathologically important signaling transduction pathways. In the presented study, we analyzed the expression and cellular distribution of EGFR family members in sporadic cardiac myxoma lesions of human heart. The study included 36 patients, who were treated with surgical excision of the lesion. Expression of EGFR1/c-erbB1, c-erbB2, c-erbB3 and c-erbB4 was studied by immunohistochemical staining and qRT-PCR. The patient population was comprised of 27 (75%) women and 9 (25%) men. The mean age of patients was 63 years, with an age range of 34 to 87 years. All studied cases were sporadic myxoma originating in the left atrium. Majority of examined cases demonstrate moderate-to-strong and overlapping expression of EGFR family protein members in all commonly present histological types of neoplastic myxoma cells except the c-erbb2 which was immunohistochemically negative (HercepTest) in all cases. c-erbB4 showed statistically significant decrease in expression on mRNA level compared to normal left atrial tissue. Compared relative quantities of EGFR protein members with each other showed that c-erbB3 and c-erbB2 were the only ones exhibiting statistically significant (p=0.01304), and positive (r=0.721) correlation. In conclusion the EGFR1/c-erbB1, c-erbB2 (mRNA only) c-erbB3 and c-erbB4 are co-expressed in the tissue of cardiac myxoma lesions and may play a distinct role in their pathogenesis