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Biomedical subjects

A Verhest

Publications and source records attributed to A Verhest.

At least 19 recordsLinked to original sources

Reliability of the tissue microarray based FISH for evaluation of the HER-2 oncogene in breast carcinoma.

AIMS: Tumour tissue microarray allows the analysis of hundreds of tumour samples simultaneously on a single microscope slide. However, the extremely small tissue samples taken from the original tissue may not always be representative of the entire tumour. METHODS: The reliability of this new technology was investigated by analysing HER-2 oncogene amplification by fluorescence in situ hybridisation (FISH) from representative slides of the whole tumour and small tissue core biopsies from 29 invasive breast tumours. RESULTS: The tissue microarray method had high accuracy; in only one of 29 cases (3.4%; 95% confidence interval, 0% to 10%) were the results discordant with whole tumour analysis. CONCLUSION: Tumour microarray is a highly reliable method for analysing HER-2 oncogene amplification by FISH in human breast tumours.

Biomarkers↗

Aggressive endometrial carcinoma in a breast cancer patient treated with tamoxifen with normal transvaginal ultrasonography. Case report.

Since tamoxifen therapy can induce endometrial disorders, surveillance schemes of women taking tamoxifen have been recommended. Transvaginal ultrasonography is a very sensitive test and therefore is often performed as a first-line screening test. We described a very atypical case of a high stage, high grade endometrial cancer associated with tamoxifen in a 64-year-old woman with a past history of breast cancer. This women was assessed yearly by ultrasonography and Pap smear. The cancer developed on a very thin endometrium and transvaginal ultrasonography failed to detect it. The patient remained asymptomatic up to the diagnosis. Normal endometrial cells in the Pap smear test were the only signs associated with this cancer. Surveillance strategies and significance of endometrial cells on the Pap smear are reviewed. In conclusion, TVUS can fail to detect cancers if the endometrial lining is not enlarged. In case of normal endometrial cells in the Pap smear, a careful evaluation should be performed.

Biopsy, Needle↗

Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.

Carcinoma, Squamous Cell↗

In situ amplification of oestrogen receptor alpha mRNA in breast cancer cell lines and tumours.

The aim of this work was to develop a direct in situ reverse transcription polymerase chain reaction (in situ RT-PCR) assay for the detection of oestrogen receptor alpha (ERalpha) mRNA on in vitro cell lines and breast tumour cell smears. ERalpha mRNA amplification was performed on MCF-7 (ERalpha positive) and MDA-MB-231 (ERalpha negative) cell lines as well as on 51 cytological smears of breast tumour samples from patients. The in situ amplification of mRNA in cell lines and ex vivo breast tumours was successful. However, finding an equilibrium between optimal cell morphology and PCR performance varied with each tumour, leading to difficulty in standardisation for daily practice. Nonetheless, in situ RT-PCR is a useful tool for the detection of ERalpha mRNA in selected cases, both in vitro and ex vivo. J Clin PATHOL: Mol Pathol

Breast Neoplasms↗

[Detection of extra chromosomes 12 by fluorescent in situ hybridization (FISH) in ovarian stromal tumors. Study of 12 cases and review of the literature].

Chromosomic aberrations play a major role in the initiation and the progression of benign as well as malignant tumors. In particular, trisomy 12 is frequently observed in female genitourinary tract tumors and constitutes a recurrent and often unique anomaly in stromal ovarian tumors such as fibrothecomas. Today, the genetic analysis of fresh or fixed solid tumors is enabled by the fluorescent in situ hybridization method (FISH). Using FISH and/or conventional cytogenetics, we analysed 12 ovarian stromal tumors (6 fibromas, 3 fibro thecomas and 3 thecomas). All of these tumors were benign and trisomy 12 was observed in all cases. Moreover, 3 cases presented trisomy and tetrasomy for chromosome 12 simultaneously. The high frequency of trisomy 12 in this tumor type suggests that this abnormality might be implicated in ovarian tumorigenesis.

Adult↗

MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23.

We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.

Adult↗

HIV-associated multinucleated giant cells in lymphoid tissue of the Waldeyer's ring: a detailed study.

Hyperplastic lymphoid tissues of the Waldeyer's ring in human immunodeficiency virus (HIV)-infected patients may occasionally contain multinucleated giant cells (MGCs). These cells, which are unrelated to any opportunistic infection, previously have been demonstrated to harbor significant amounts of HIV. Studies undertaken to characterize these MGCs have generated conflicting results: some reports suggested a macrophage origin, whereas others supported a dendritic cell lineage. This study was performed to determine the occurrence of MGCs in a series of adenoid/tonsil specimens from HIV-seropositive patients showing no histological evidence of opportunistic infection in order to further characterize the phenotype of these cells and to investigate the role of a viral infection in their pathogenesis. Adenoid/tonsil tissue specimens from 21 HIV-seropositive patients with no documented opportunistic infection were scrutinized for the presence of MGCs and evaluated immunohistochemically on paraffin sections by antibodies directed against various macrophage and DC antigens. These antigens included CD68, the macrophage marker 3A5, major histocompatibility complex Class II, S-100 protein, CD1a, and CD83. Additional immunostainings directed at CD21 and CD35 as well as at the HIV-associated p24 antigen were also performed. Finally, the presence of Epstein-Barr virus and human herpesvirus 8 viral sequences was investigated by in situ hybridization and by polymerase chain reaction analysis, respectively. MGCs were found in 14 patients (66.7%), regardless of gender, age, method of viral transmission, CD4 cell count, viral load, or ethnic group. These cells were mostly localized at the lymphoepithelium layer of the tonsillar crypts and, to a lesser extent, in the interfollicular areas of the underlying lymphoid tissue, which consistently exhibited features of follicular hyperplasia. Phenotypically, MGCs were found to be CD68+, 3A5+, major histocompatibility complex Class II+, S-100 protein+/-, CD1a-, CD21-, CD35-, and CD83-. Although the HIV-associated p24 protein was consistently present in the cytoplasm of these cells, no sign of Epstein-Barr virus or human herpesvirus 8 infection could be demonstrated. Consequently, our study didn't show any conclusive evidence to support that MGCs in hyperplastic lymphoid tissues of the Waldeyer's ring from HIV-seropositive patients originated from dendritic cells. The definite nature of these cells has yet to be elucidated, but it is plausible that they simply represent activated macrophages that are infected with HIV present in the oropharyngeal secretions during the circulation of their precursor through the lymphoepithelium area of adenoids and tonsils.

Adenoids↗

Trisomy 6 in Merkel cell carcinoma: a recurrent chromosomal aberration.

UNLABELLED: We retrospectively investigated 17 cases of primary and metastasizing Merkel cell carcinomas (MCC) from 14 patients using chromosomal in-situ hybridization (CISH) to study the occurrence of trisomy 6 in these lesions. METHODS AND RESULTS: Histological diagnosis on all tumour samples was obtained on haematoxylin and eosin stained sections. Immunohistochemistry was performed with antibodies against pancytokeratin (CAM 5.2), cytokeratin 20 (CK20), MIC2 antigen (CD99), neuron-specific enolase (NSE), and chromogranin A (chrA). Sections (4 microm) of the paraffin-embedded tumours were analysed with alpha-satellite centromeric probes for chromosome 6 or 17 using CISH. The signal was amplified by the Tyramide Signal Amplification (TSA) assay. Immunohistochemically, the tumours showed the same general epithelial neuro-endocrine pattern: 11/13 expressed cytokeratin 20, and 47% exhibited trisomy 6, with no significant difference between primary and metastatic lesions. Incomplete follow-up data did not allow us to establish a prognostic value of trisomy 6, however, this aberration might be an additional diagnostic tool in distinguishing MCC from other small round blue cell tumours. CONCLUSIONS: CISH seems to be a promising adjunctive method to diagnose Merkel cell carcinoma. Trisomy 6 should be investigated more closely in these cases, as has been done for chromosomes 1 and 11. Of particular interest would be identification of modifications in proto-oncogene(s) located on chromosome 6.

Aged↗

Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. Correlation with oncogene amplification in 160 cases.

Overexpression and amplification of the HER-2 oncogene in patients with breast cancer has correlated with early onset of metastasis, resistance to hormonal therapy and some forms of chemotherapy, and shortened survival. Therefore, evaluation of this putative prognostic or predictive factor seems critical. Because different antibodies are used for the detection of the 185-kd HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibodies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpression was found in 17.2% and 12.5% of cases using antibodies against the external (TAB250) and internal (CB11) domains of the protein, respectively, and in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in situ hybridization was successful in all 160 tumors, and amplification was found in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misclassification rate, 9.6% (sensitivity, 67%; specificity, 97.5%).

Antibodies↗

Tumor-infiltrating dendritic cells in adenocarcinomas of the breast: a study of 143 neoplasms with a correlation to usual prognostic factors and to clinical outcome.

Dendritic cells (DC) are the most potent antigen-presenting cells, and induce antigen-specific immune responses. Infiltration of tumors by DC is thought to reflect the interaction between the host immune system and tumor cells. Tumor-infiltrating DC (TIDC) are believed to evolve into tumor-antigen pulsed cells and then to migrate to local lymph nodes, where they activate anti-tumor immune responses. Indirect clinical evidence supporting this theory is provided by studies showing that high TIDC densities are associated with favorable prognosis in some tumor types. In the present study, we evaluated 143 primary breast adenocarcinomas for the presence of DC, using immunohistochemistry with the anti-S100 protein antibody. We analyzed the relationship between the degree of infiltration by S100+ TIDC and the usual prognostic factors and clinical outcome. The results show that 42% of breast adenocarcinomas contain S100 TIDC. The number of S100+ TIDC varies according to the grade of tumors as follows: GRIII > GRII > GRI. A relationship is also found between S100+ TIDC and tumor size, lymph-node involvement, estrogen/progesterone receptor status and age. However, the presence of S100+ TIDC, even at the highest density, was not correlated with metastasis-free survival or overall survival.

Adenocarcinoma↗

Trisomy 21 as the sole abnormality in a refractory anemia with ring sideroblasts.

Numerous chromosome abnormalities have been described in myelodysplastic syndromes, but single karyotypic aberrations are much less frequent. We report the case of a 65-year-old woman who presented a trisomy 21 as the sole karyotypic anomaly for a refractory anemia with ring sideroblasts. The nature of such an anomaly is discussed in regard to pathogenesis and prognosis.

Aged↗

Detection of bronchial preneoplastic lesions and early lung cancer with fluorescence bronchoscopy: a study about its ambulatory feasibility under local anaesthesis.

BACKGROUND: Autofluorescence bronchoscopy (AB) enhances the bronchoscopist's ability to diagnose bronchial preneoplastic lesions and early cancer. We undertook a study to assess its feasibility and performance under local anaesthesia on a real ambulatory mode. METHODS: Thirty-four consecutive patients at very high risk for lung cancer were prospectively studied by AB under local anaesthesia, without any sedation. Lidocaine doses, time, oxygen saturation, peak expiratory flow (PEF) and the number of cough episodes were measured. Continuous assessment of the respiratory sensation was obtained with a visual analog scale. A total of 172 biopsies were performed in abnormal and normal areas. RESULTS: The procedure was long-lasting (mean +/- SD: 26.6 +/- 6.0 min), required high total doses of Lidocaine (660 +/- 107 mg) without any significant side effect, and was associated with significant decreases in O2 saturation from 98.5 +/- 1.4 to 96.1 +/- 2.5% and in PEF from 380 +/- 96 to 310 +/- 78 l/min. However, the cough counts were moderate and the majority of patients reported no respiratory discomfort. 62 hyperplasia, metaplasia, dysplasia and carcinoma in situ (CIS) were detected and the relative sensitivity of AB +/- white-light bronchoscopy (WLB) versus WLB alone was 3.75 for intraepithelial lesions corresponding to moderate dysplasia or worse. CONCLUSIONS: AB, a procedure that increases our ability to recognize preneoplastic lesions and early lung cancer, can be performed under local anaesthesia, without systemic sedation in patients at very high risk for lung cancer.

Ambulatory Care↗

Carbonic anhydrase IX antigen differentiates between preneoplastic malignant lesions in non-small cell lung carcinoma.

The MaTu interval (MN)/carbonic anhydrase (CA) IX tumour-associated antigen is a protein that is normally expressed in the gut and belongs to the carbonic anhydrase enzyme family (CA IX). It has been detected in tumour cell lines and in some solid tumours including cervical, oesophageal and clear cell renal carcinoma. This study determined MN/CA IX expression in 65 primary non-small cell lung cancer resected with curative intent and in 38 bronchial preneoplastic lesions, carcinoma in situ or microinvasive carcinoma as well as in normal bronchial tissue. The presence of MN/CA IX was detected using immunohistochemistry and Western blot analysis, whenever frozen material was available. Immunostaining was positive in 52/65 (80%) of the tumour samples. The staining was more often focal than diffuse. The percentage of stained cells in positive tumours was highly variable, ranging 1-85%. The pattern of immunostaining was predominantly cytoplasmic with a membranous reinforcement (87%). The intensity was mainly strong (69%). The presence of the protein in the tumour was confirmed by Western blot analysis in the eight samples tested. All the morphologically normal epithelia, except in close vicinity of tumours in some cases, as well as the preneoplastic bronchial lesions (basal cell hyperplasia, metaplasia and dysplasia) were immunonegative for MN/CA IX expression. In contrast, carcinoma in situ and microinvasive epithelioma showed the presence of MN-immunopositive tumoural cells in 5/7 and 4/5 of the samples, respectively. These data suggest that MN/CA IX is a useful marker for the differentiation between preneoplastic lesions and bronchial non-small cell lung cancer in the lung.

Adenocarcinoma↗

[Anatomical-clinical conference: mediastinal mass].

A 56 years-old man developed a pneumonia. An anterior mediastinal mass is fortuitly found on the chest X-ray and the patient is hospitalised for further investigations. Differential diagnosis of mediastinal masses is discussed.

Biopsy↗

[Role of cytology and frozen sections in the intraoperative examination of the thyroid: comparison of two experiences].

Two experiences of peroperative diagnosis in thyroid surgery are reported. In Bordeaux (France), frozen sections are supplemented by touch smears. Imprints alone give results similar to frozen but are not suitable in differentiating follicular adenoma from carcinoma; they appear more accurate for recognising the follicular presentation of papillary carcinoma. Touch smear is a rapid cost-effective alternative to frozen section. In Brussels (Belgium), a more conventional attitude results in 185 frozen. A false negative ends in a follicular carcinoma. Eleven follicular proliferations will be signed out adenoma (8 cases) or carcinoma (3 cases) and three papillary carcinomas will only be detected after embedding. Six false negative derive from frozen section, no false positive is noted. An immediate change in the surgical procedure is justified twice. These observations argue for the free choice by the pathologist of the best technical procedure in peroperative diagnosis.

Adenoma↗

Primary low-grade B-cell lymphoma of MALT-type occurring in the liver: a study of two cases.

BACKGROUND/METHODS: Primary non-Hodgkin's lymphomas of the liver are rare. One specific clinico-pathological entity has been identified as hepatosplenic gamma/delta T-cell lymphoma. Recently, another distinct primary lymphoma of the liver has been recognised as primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), based on a study comprising four cases. We analysed two additional cases of this particular non-Hodgkin's lymphoma, not only by morphology and phenotyping, but also by genotyping and cytogenetic analysis. RESULTS: This type of non-Hodgkin's lymphoma is characterised by a dense lymphoid infiltrate, localised in the portal tracts, and is associated with lympho-epithelial lesions of the bile ducts, thereby mimicking hepatitis or an inflammatory bile duct disorder. In one of our cases, translocation t(3;14)(q27;q32) was identified as the sole cytogenetic abnormality. A high incidence of trisomy 3 has been associated with marginal zone B-cell lymphomas, and fluorescence in situ hybridisation as well as comparative genomic hybridisation studies have shown frequent involvement of the long arm of chromosome 3. Nevertheless, t(3;14)(q27;q32) involving BCL6 gene, located at 3q27, has not yet been found. CONCLUSION: Our findings suggest a role for the BCL6 gene in the histogenesis of this particular lymphoma.

Antigens, CD↗

Complete remission following donor PBSC after low-dose cytarabine chemotherapy for early relapse of acute myelogenous leukemia after allogeneic stem cell transplantation.

A 55-year-old woman with chemotherapy-resistant acute myeloblastic leukemia (AML M2) relapsed 3 months after allogeneic PBSC transplant. The patient was treated with two cycles of low-dose cytarabine chemotherapy followed by G-CSF mobilized donor PBSC after cessation of all immunosuppressive treatment. Hematological and cytogenetic complete remission was observed after the first cycle. The patient had been previously treated for AGVHD after allogeneic PBSC transplantation and experienced a second AGVHD after the second cycles of cytoreductive treatment and donor PBSC infusion. Hematological recovery after donor PBSC infusion was faster than recovery after previous chemotherapy or high-dose chemotherapy. During treatment no febrile neutropenia was observed. This case shows that donor PBSC infusion cannot only provide prolonged complete hematological and cytogenetic remission but also seems to support accelerated hematopoietic recovery for some patients relapsing after allogeneic BMT.

Antimetabolites, Antineoplastic↗