Patterns of ALK expression in different human cancer types.

AIMS: Oncogenic gene fusions involving the anaplastic lymphoma kinase (ALK) tyrosine kinase have been identified in several haematopoietic and sporadically also in solid tumour types. Preliminary results from clinical trials suggest that patients with ALK fusion positive cancers might optimally benefit from the tyrosine kinase inhibitor crizotinib, but a comprehensive analysis of solid tumour types for ALK fusion and fusion associated expression is lacking. METHODS: In order to identify human solid cancers carrying ALK alterations, we performed real-time PCR screening of 1000 tumour samples representing 29 different tumour entities. ALK-positive samples were then transferred into a tissue microarray format and subjected to ALK break-apart fluorescence in situ hybridisation (FISH) analysis and ALK immunohistochemistry (IHC) analysis. RESULTS: ALK expression was detected by real-time PCR in 260 of 896 (29%) interpretable tumour samples. FISH analysis was successful in 189 of 260 arrayed cancers but did not detect ALK rearrangement. There was also no ALK expression detectable by IHC. CONCLUSIONS: Different levels of ALK expression can be found in various cancer types using sensitive methods like real-time PCR. However, such low-level expression is independent from oncogenic ALK fusions and cannot be detected with less-sensitive methods like IHC. ALK fusion is a rare event in human solid cancers.

Patterns of TPD52 overexpression in multiple human solid tumor types analyzed by quantitative PCR.

Tumor protein D52 (TPD52) is located at chromosome 8q21, a region that is frequently gained or amplified in multiple human cancer types. TPD52 has been suggested as a potential target for new anticancer therapies. In order to analyze TPD52 expression in the most prevalent human cancer types, we employed quantitative PCR to measure TPD52 mRNA levels in formalin-fixed tissue samples from more than 900 cancer tissues obtained from 29 different human cancer types. TPD52 was expressed at varying levels in all tested normal tissues, including skin, lymph node, lung, oral mucosa, breast, endometrium, ovary, vulva, myometrium, liver, pancreas, stomach, kidney, prostate, testis, urinary bladder, thyroid gland, brain, muscle and fat tissue. TPD52 was upregulated in 18/29 (62%) tested cancer types. Strongest expression was found in non-seminoma (56-fold overexpression compared to corresponding normal tissue), seminoma (42-fold), ductal (28-fold) and lobular breast cancer (14-fold). In these tumor types, TPD52 upregulation was found in the vast majority (>80%) of tested samples. Downregulation was found in 11 (38%) tumor types, most strongly in papillary renal cell cancer (-8-fold), leiomyosarcoma (-6-fold), clear cell renal cell cancer (-5-fold), liposarcoma (-5-fold) and lung cancer (-4-fold). These results demonstrate that TPD52 is frequently and strongly upregulated in many human cancer types, which may represent candidate tumor types for potential anti-TPD52 therapies.