Etienne-Grimaldi M.-C.,Center Antoine Lacassagne |
Mahamat A.,Nice University Hospital Center |
Chazal M.,Clinique Saint George |
Laurent-Puig P.,French Institute of Health and Medical Research |
And 18 more authors.
British Journal of Cancer | Year: 2014
Background:To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours.Methods:This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH.Results:The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR.Conclusions:Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy. © 2014 Cancer Research Uk.
Magrangeas F.,University of Nantes |
Avet-Loiseau H.,University of Nantes |
Gouraud W.,University of Nantes |
Gouraud W.,Institute Of Cancerologie Of Louest |
And 19 more authors.
Leukemia | Year: 2013
Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-κB-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission. © 2013 Macmillan Publishers Limited All rights reserved.
Mourra N.,Ho Pital St Antoine |
Arrive L.,Ho Pital St Antoine |
Balladur P.,Ho Pital St Antoine |
Flejou J.-F.,Ho Pital St Antoine |
And 2 more authors.
Pancreas | Year: 2010
Objectives: Metastatic tumors to the pancreas are rare and usually present a part of an advanced metastatic disease. Isolated metastasis is even rarer and may be difficult to differentiate from primary pancreatic neoplasm. The leading sources of metastases are breast, lung, kidney, and skin (melanoma). We present our experience with 12 cases of isolated pancreatic metastasis. Methods: We made a retrospective review from a series of pancreatic resections for metastatic disease, which occurred during the last decade. Results: The sites of origin were as follows: kidney (8 cases), lung (2 cases), bone (1 case), and breast (1 case). Only 4 patients were symptomatic (abdominal pain, 3 cases; melena, 1 case). The metastasis was metachronous in 11 cases, with mean disease-free interval of 9 years. The preoperative diagnosis was endocrine tumor in 4 cases. All patients underwent complete extirpation.At the time of follow-up, 3 patients had died of malignancy and 9 were still alive and free of disease, with a mean follow-up of 3 years. Conclusions: Isolated metastatic tumors to the pancreas may be detected decades after the initial diagnosis and can be asymptomatic, emphasizing the need for lifelong surveillance in this population. Surgical extirpation of these lesions may offer the chance of long-term survival. © Copyright 2010 by Lippincott Williams & Wilkins.