gms | German Medical Science

Objective: The incidence of brain metastases (BM) in lung cancer is as high as 30%. In this study, we tested the hypothesis whether there is a specific genotype for the metastatic spread to the brain of lung cancers (LC) of different histologies.

Method: We studied a total of 89 paraffin-embedded BM of 22 small cell (SCLC), 32 squamous (SQC), 16 ADC, 11 adenosquamous (ADSQ) as well as 8 large cell tumors (LCC) using comparative genomic hybridization (CGH). The CGH results of the brain metastases were compared to those of 308 primary lung cancers (71 SCLC, 121 SQC, 95 ADC, 2 ADSQ and 19 LCC), taken from literature searching MEDLINE, Progenetix, Mitelman- and SKY/M-FISH&CGH-database. Statistical differences of chromosomal aberrations between primary tumors and brain metastases of the same histological type where analysed using the χ-test, adjusting p-values for a false-discovery-rate.

Results: In small cell lung cancer (SCLC), the most relevant differences were seen for gains of 5q11 and 19, as well as for losses at 3q11, 4q32q33, 5p11, 13p11 and 17q11 (p for all <0.01). In SQC, brain metastases significantly more often showed gains of 1q12q21 (p=0.02), 2q12q14 (p=0.04), 6p12p21 (p=0.04), 7q21 (p<0.01), 10p13pter (p=0.03) and 19q12 (p=0.03), as well as losses to 5p12pter (p=0.03), 8p12pter (p=0.03), 9p13pter (p=0.04), 13q21qter (p=0.03) and 18q (p<0.01). In contrast, primary SQC significantly more often revealed gains of 3p11 and 5q11 (both p<0.01) as well as losses to 16p11q11 (p=0.02). In ADC, BM significantly more often harboured losses of 11p13p14 (p=0.02), 18q23 (p=0.03) and to 22q11 (p=0.01), whereas again gain of 5q11 was significantly more often seen in primary tumors (p=0.01). No statistical analyses were performed for ADSQ and LCC cancers because of the low tumor numbers.

Conclusions: From our results, a metastastic genotype for brain metastases of non-SCLC seems reasonable. As in BM of both ADC and SQC, gains of 1q12q21 and losses to 8p, 9p and 18q are found significantly more frequently. Most astoninglishly, all primary lung cancers, regardless of the histological subtype, significantly more often harboured gains on 5q11. Further investigations on oncogenes at 5q11 should be performed, as this may help to impede the metastatic spread of tumor cells to the brain.