This study presents a new technique for the orthotopic engraftment of
human lung tumours in SCID mice and demonstrates the importance of a m
ore clinically relevant route of tumour propagation for the study of m
etastatic potential. The orthotopic engraftment of human lung tumour b
iopsy specimens was performed via an anterior thoracotomy into SCID mi
ce. Engraftment of non-small cell lung cancer specimens from nine pati
ents into 52 SCID mice yielded a 31% engraftment rate and a 50% metast
asis rate. Unlike subcutaneous inoculation, the engraftment rates foll
owing the orthotopic inoculation did not vary between squamous cell ca
rcinomas and adenocarcinomas. Direct visceral pleural invasion was see
n in most cases. Orthotopically placed tumours grew 5-fold by 4 to 6 m
onths. Unique to this model was the observation of metastasis to clini
cally relevant sites, such as the adrenal gland and supraclavicular ly
mph nodes. Contralateral lung metastases were also noted in 37.5%, and
one ovarian metastasis occurred. The procedure was well tolerated, wi
th survival rates of 98%.