Naslov
Brain metastases from lung cancer show frequent changes of E-cadherin, APC and beta-catenin genes

Autori
Pećina-Šlaus, Nives ; Zeljko, Martina ; Kafka, Anja ; Tomas, Davor

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts 4th Croatian Congress of Neuroscience / / - Zagreb : Hrvatsko društvo za neuroznanost ; Hrvatski institut za istraživanje mozga Medicinskog fakulteta Sveučilišta u Zagrebu, 2013, 31-32

Skup
4th Croatian Congress of Neuroscience

Mjesto i datum
Zagreb, Hrvatska, 20.09.2013. - 21.09.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
brain metastases; E-cadherin; APC; beta-catenin

Sažetak
The susceptibility of brain to secondary formation from lung cancer primaries is a well known phenomenon. On the contrary, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study 25 brain metastases that originated from primary lung carcinomas were analyzed regarding changes of E-cadherin (CDH1), APC (adenomatous polyposis coli) and beta-catenin (CTNNB1) genes. Genetic changes of E-cadherin and APC were tested by PCR/loss of heterozygosity (LOH) method using D16S752, D16S265 and D16S398 microsatellite markers for CDH1 gene and RFLP method performed by the use of Msp I and Rsa I genetic markers for the APC gene. Heteroduplex method was used to investigate potential mutations in beta-catenin. Protein expressions and localizations were analyzed by immunohistochemistry. The results showed altogether 36% of samples with LOH of the CDH1 gene assessed with 3 markers. The highest frequency of genetic changes was observed in the metastases originating from primary sites of lung adenocarcinoma and small cell lung cancer (SCLC) with 83.3% and 75% of genetic changes, respecitively, while squamous cell carcinoma showed 25% and large cell carcinoma 12.5% of changes. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and SCLC were significantly associated to E-cadherin genetic changes with 2= 10.364 ; df=1 ; P=0.001. Microsatellite instability (MSI) was detected in one adenocarcinoma. Exon 3, the mutational hot-spot of beta-catenin, was not targeted. Immunostaining showed that overall 76% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in 52% of metastases. The majority of samples with LOH (88.9%) were accompanied with the downregulation of E-cadherin protein expression. The main effector of the wnt signaling, beta-catenin, was upregulated in 54, 2%, and transferred to the nucleus in 33, 3% of metastases. Among 14 brain metastases available for the analysis of the APC gene 11 were informative and 6 demonstrated LOH (55%). Somatic mutation in exon 15 of the APC gene was also detected in one case of adenocarcinoma by direct DNA sequencing of the metastasis and autologous lymphocyte samples. The substitution was at position 5883 G–A in the metastasis tissue.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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