2012/09/06 00:40

Histology for ALK translocation


The fusion between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic
lymphoma kinase (ALK) has recently been identified in a subset of non-small cell lung cancers
(NSCLCs). EML4-ALK is most often detected in never smokers with lung cancer and has unique
pathologic features. EML4-ALK is oncogenic both in vitro and in vivo and ALK kinase inhibitors are
quite effective in pre-clinical model systems. More recently ALK inhibitors have entered clinical
development and remarkably clinical efficacy has been observed in NSCLC patients harbouring
EML4-ALK translocations.


The fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubuleassociated
protein-like 4 (EML4) was identified in 2007 in Japanese non-small cell lung
cancers (NSCLC) 4. Additional studies, mostly involving East Asian patients, have reported
that between 3%–13% of lung tumors harbor EML4-ALK fusions4–11. By extrapolation this
would suggest that approximately 5% of all NSCLC cases contain an EML4–ALK
translocation, equivalent to over 70,000 patients diagnosed annually worldwide.


A variety of histologic features are reported to be associated with ALK-rearranged lung
adenocarcinomas including acinar (ranging from well-differentiated tubulopapillary and
cribriform patterns) to mostly signet-ring cell nests with mucin production
. Other
histologic types such as squamous cell carcinoma and mucoepidermoid carcinoma also rarely
contain EML4-ALK translocations
.


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