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Laurence Lespagnard

Publications and source records attributed to Laurence Lespagnard.

8 recordsLinked to original sources
PubMed2006

Correction for chromosome-17 is critical for the determination of true Her-2/neu gene amplification status in breast cancer.

PURPOSE: Trastuzumab is the cornerstone for treatment of women with HER2-overexpressing breast cancer, both in the adjuvant and in the metastatic settings. The accurate assessment of HER2 is, therefore, critical to identifying patients who may benefit from trastuzumab-based therapy. This project aimed to determine the optimal scoring method for fluorescence in situ hybridization (FISH) assay. METHODS: FISH assay was done on 893 samples of breast cancer. Three scoring methods were evaluated: Her2/CEP17> or =2, Her2>4, or Her2>6. Protein and gene expression were evaluated by immunohistochemistry (n = 584) and mRNA/assay/nucleic acid sequence-based amplification (NASBA; n = 90). RESULTS: Samples were divided into five groups based on FISH results: disomic amplified and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of cases, mostly positive with Her2>4 scoring, but negative with the others). Her2/CEP17> or =2 and Her2>6 scoring methods showed the best association (a) with regard to FISH scoring (kappa = 0.906, P < 10(-6)) and (b) between FISH and immunohistochemistry (3+ as positive; kappa > 0.650, P < 10(-6)) or NASBA (kappa > 0.536, P < 10(-6)). Polysomy had an effect on Her2 copy number (P < 10(-6)), but had no effect on protein and mRNA content. Therefore, within the discordant subgroup, for which additive Her-2 gene copies are due to high polysomy, protein and mRNA levels were similar to those of the nonamplified samples. For this subgroup, the best concordance between FISH/immunohistochemistry/NASBA was observed with the Her2/CEP17 ratio and Her-2>6 scoring (68% and 58% perfect matches, respectively). No perfect matches were observed using the Her2>4 scoring method. CONCLUSION: Correction for chromosome-17 is the method of choice for clinical practice; Her-2>6, but not Her-2>4, could be used as an alternative.

Aneuploidy↗
PubMed2005

Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily practice.

PURPOSE: To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers. EXPERIMENTAL DESIGN: HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)-approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases. RESULTS: When a ratio > or = 2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number >4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number >4 and 1.1% (5 of 440) with a ratio > or = 2 had a net HER-2/neu gene copy number <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0. CONCLUSION: A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.

Breast Neoplasms↗
PubMed2005

De novo CD5-positive diffuse large B-cell lymphoma of the skin arising in chronic limb lymphedema.

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature.

Aged↗
PubMed2002

Diffuse large B-cell lymphoma with fibrillary matrix.

Diffuse large B-cell lymphoma (DLBCL) with fibrillary matrix is an extremely rare variant of non-Hodgkin's lymphoma (NHL) whose pathological features are poorly known. Here, we report on our experience with such a condition arising in a 71-yr-old woman. Our findings not only demonstrate that DLBCL with fibrillary matrix actually represents a peculiar subtype of DLBCL, but they also illustrate that the cytologic and flow cytometric features in this disorder can be deceptive enough as to mislead even the most experienced cytopathologist.

Aged↗
PubMedDate not supplied

Primary cutaneous marginal zone B-cell lymphoma of MALT type in a child.

Marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue type is a peculiar variant of B-cell neoplasm showing distinct clinical and pathologic features. Its occurrence in children or adolescents is extremely uncommon. We describe the case of an 11-year-old boy who developed such a lymphomatous process involving primarily the skin. The tumor was characterized by a maturing plasma cell population that included immunoblasts, heavy-chain but not light-chain restriction suggestive of monoclonality, and a prevalent, focally granulomatous component of histiocytes. As an additional interesting feature, a trisomy 3 was demonstrated by fluorescence in situ hybridization analysis. The clinical, morphological, phenotypic, and genetic characteristics seen in our patient do not differ significantly from those described in primary cutaneous MZBCL occurring in adults.

Biomarkers, Tumor↗