Gene expression analysis facilitates the detection of diagnostic and prognostic biomarkers for myeloid haematological malignancies. The Oncomine Myeloid Research Assay (OMA; Thermo Fisher Scientific, Massachusetts, USA) provides a comprehensive analysis of gene expression of five target genes, along with gene alteration and fusion. Here, we present the performance of the OMA for gene expression analysis.In total, 53 RNA samples from patients diagnosed with acute myeloid leukaemia (AML) or myelodysplastic syndrome were included. Of these 53 samples, 3 were evaluated for reproducibility and 50 were evaluated for comparison with RNA-sequencing (RNA-seq). The prognostic impact of the gene expression profile produced by both OMA and RNA-seq in AML was investigated using follow-up data from 33 patients with AML.The OMA showed good intrarun and interrun reproducibility. Compared with the RNA-seq results, high correlations were found in BAALC, MECOM and WT1 (all r>0.9), with moderate correlations in MYC (r=0.75, p<0.001) and SMC1A (r=0.42, p=0.002). The agreement between OMA and RNA-seq in classifying the dysregulated expression group was almost perfect, except for SMC1A (κ=0.175). Among these five genes, only BAALC showed a significant clinical impact in patients with AML. Patients with high BAALC expression showed significantly shorter overall survival based on both OMA (p=0.037) and RNA-seq (p=0.003).OMA gene expression analysis offers reproducible and accurate gene expression data for most targeted genes and demonstrates the utility of BAALC expression as a prognostic marker in AML.
<b><i>Background:</i></b> The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. <b><i>Methods:</i></b> From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. <b><i>Results:</i></b> The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). <b><i>Conclusions:</i></b> CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1.
6118 Background: Since 2002, several drugs (including bevacizumab (Bv), oxaliplatin (Ox), irinotecan (Iri)) have been approved for mCRC. The goals of this study are to examine patterns of newer chemotherapy (CTx) use and survival trends in older mCRC pts. Methods: Pts ≥ age 65 with mCRC diagnosis (dx) 2001–5 were identified from the SEER–Medicare database. Pts were excluded for Medicare HMO, lack of Medicare parts A and B, or second cancer. First–line (1L) CTx was identified within 3 mo of dx. Pts were categorized by dx year (2001–3 vs. 2004–5) and treatment (none, CTx, CTx + Bv.). A logistic regression model identified factors associated with 1L Bv use. A Cox proportional hazards regression model was used to assess association of various factors (age, comorbidity, hepatic resection (rsxn), CTx) with survival. Results: 5,725 pts (median age 77) met criteria, of whom 2,647 (46%) received 1L CTx. In 2004–5, 32% and 12% of treated pts received Ox and Iri (vs.1% and 34% in 2001–3). Following its approval in 2004, 25% of treated pts received Bv. Factors associated with 1L Bv use include age <75 (OR 1.43, p=0.02) and concurrent use of Ox (OR 10.11, p<0.001) or Iri (OR 5.82, p<0.001). In a Cox proportional hazards model, survival was greater in pts with lower comorbidity, age <75, hepatic rsxn, 1L CTx use, and dx 2004–5. Pts dx 2004–5 who used Bv had the greatest survival compared with untreated pts dx 2001–3 (HR 0.46, p<0.001, median OS 15 vs. 6 mo). Conclusions: In an elderly mCRC cohort, nearly half of pts received 1L CTx, many with regimens containing Iri, Ox, or Bv. Survival was greatest in pts dx 2004–5 who used Bv. Increased Ox use may also have improved survival in this period. Future SEER–Medicare analyses may help elucidate the relative benefit of other new agents in the elderly, a population under–represented in clinical trials. Cox proportional hazards model. Factor HR 95% CI P Age < 75 0.71 0.66 – 0.75 <0.001 Comorbidity (Klabunde) ≤ 1 0.75 0.70 – 0.80 <0.001 Hepatic rsxn 0.68 0.58 – 0.79 <0.001 Dx 2001-3 + 1L CTx 0.84 0.78 – 0.91 <0.001 Dx 2004-5 no 1L CTz 0.88 0.81 – 0.95 0.002 Dx 2004-5 + 1L CTx 0.63 0.57 – 0.69 <0.001 Dx 2004-5 + 1L CTx and Bv 0.46 0.39 – 0.55 <0.001 Reference: Age ≥ 75. Comorbidity >1, No hepatic rsxn, Dx 2001-3 no 1L CTx
The aim of this study was to analyze expression of hMLH1 and hMSH2 mismatch repair proteins in terms of p53 protein expression and clinicopathological parameters in sporadic colorectal cancer.Four hundred and two cases of curative colorectal surgery for primary colorectal cancer were included in this study (patients with a familial history of colorectal cancer and familial adenomatous polyposis were not included). Clinicopathological parameters were reviewed retrospectively. HMLH1, hMSH2 and p53 protein expression in tumor tissue sections was determined using immunohistochemical staining with specific monoclonal antibodies.Of the 402 cases, immunohistochemical analysis showed 35 (8.7%) had loss of expression of hMLH1, 19 (4.7%) had loss of expression of hMSH2, and three cases (0.7%) had loss of expression of both proteins. Multivariate analysis showed that early age of onset (p=0.023), right side dominance (p<0.001) and poorly differentiated or mucinous cell type (p<0.001) were associated with loss of expression of hMLH1 or hMSH2. Loss of expression of hMLH1 or hMSH2 correlated with low p53 expression (p<0.001). In terms of clinicopathological parameters, p53 expression was associated only with hMLH1 or hMSH2 expression.Colorectal cancers not expressing hMLH1 or hMSH2 may have distinct features from those expressing these mismatch repair proteins. p53 expression appears to be implicated in a compensatory pathway with mismatch repair proteins.
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