Search tips
Search criteria

Results 1-4 (4)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas 
Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK.
In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of ALK rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5′ end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3′ end of the ALK signal. Two patients showed a deletion of the 3′ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR mutation (T790M) was detected. Two KRAS mutations were detected among 24 ALK-rearranged samples tested.
In a large unselected series, the frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR mutations were seen.
PMCID: PMC3576271  PMID: 23198868
ALK rearrangement; ALK amplification; FISH; KRAS; EGFR; Non-small cell lung cancer; Adenocarcinoma; Crizotinib
2.  Soluble syndecan-1 (sCD138) as a prognostic factor independent of IgVH mutation status in patients with chronic lymphocytic leukemia 
Syndecan-1 (sCD138) is a transmembrane heparin sulfate-bearing proteoglycan expressed in epithelial cells as well as hematopoietic cells that demonstrate plasmacytoid differentiation. Higher levels of sCD138 correlate with poor outcome in myeloma. We examined the association of circulating sCD138 levels in plasma with clinical behavior in 104 patients with chronic lymphocytic leukemia (CLL). sCD138 levels were significantly higher in patients (median, 52.8 ng/mL; range, 13.4–252.7 ng/mL) than in healthy control subjects (median, 19.86; range, 14.49–33.14 ng/mL) (P <0.01). Elevated sCD138 (> median, 52.8 ng/mL) was associated with significantly shorter survival (P = 0.0004); this association was independent of IgVH mutation status, β2-microglobulin (β2-M) level, and treatment history. Patients with mutated IgVH but high sCD138 levels (>52.8 ng/mL) had significantly shorter survival than those with mutated IgVH and lower levels of sCD138. Similarly, patients with unmutated IgVH but high sCD138 levels had significantly shorter survival than those with lower sCD138 levels and unmutated IgVH (P = 0.007). In a multivariate Cox regression model, only Rai stage, β2-M, and sCD138 remained predictors of survival. These data suggest that sCD138 when combined with β2-M and Rai stage, may replace the need for testing IgVH mutation status.
PMCID: PMC4163781  PMID: 18190591
3.  Proteasome Enzymatic Activities in Plasma as Risk Stratification of Patients with Acute Myeloid Leukemia and Advanced Myelodysplastic Syndrome 
Cytogenetic abnormalities are currently the most important predictors of response and clinical outcome for patients with acute myeloid leukemia (AML) or advanced-stage myelodysplastic syndrome (MDS). Because clinical outcomes vary markedly within cytogenetic subgroups, additional biological markers are needed for risk stratification.
Experimental Design
We assessed the utility of measuring pretreatment proteasome chymotrypsin-like (Ch-L), caspase-like (Cas-L), and trypsin-like (Tr-L) activities in plasma to predict response and survival of patients with AML (n=174) or advanced-stage MDS (n=52).
All three enzymatic activities were significantly (P<0.001) increased in the plasma of patients with AML and MDS as compared with normal controls. Both Ch-L and Cas-L activities, but not Tr-L activity correlated with outcome. Ch-L and Cas-L activities, but not Tr-L activity predicted response in univariate analysis (P = 0.002). However, only Ch-L activity was independent predictor of response from age grouping (< vs ≥70 years), cytogenetics, and BUN in multivariate analysis. Similarly, both Ch-L and Cas-L activities, but not Tr-L activity were predictors of overall survival in univariate analysis (P <0.0001), but only Ch-L activity was independent of cytogenetics, age, performance status, BUN, and beta-2 microglobulin in multivariate Cox regression models. Ch-L activity was also a strong independent predictor of survival in patients with intermediate karyotype (n=124).
Measuring plasma chymotrypsin-like activity may provide a powerful biomarker for risk stratification in patients with AML and advanced-stage MDS, including those with normal karyotype.
PMCID: PMC4091712  PMID: 19458051
acute myeloid leukemia; myelodysplastic syndrome; proteasome, chymotrypsin-like activity; survival; response; nomogram

Results 1-4 (4)