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201. The role of molecular analysis of immunoglobulin and T cell receptor gene rearrangements in the diagnosis of lymphoproliferative disorders

Author

Langerak, A.W. (Anton), Krieken, J.H.J.M. (Han) van, Wolvers-Tettero, I.L.M. (I. L M), Kerkhof, E. (E.), Mulder, A.H. (Andries), Vrints, L.W.M.A. (L. W M A), Coebergh, J.W.W. (Jan Willem), Schuuring, E. (Ed), Kluin, P.M., Dongen, J.J.M. (Jacques) van, Langerak, A.W. (Anton), Krieken, J.H.J.M. (Han) van, Wolvers-Tettero, I.L.M. (I. L M), Kerkhof, E. (E.), Mulder, A.H. (Andries), Vrints, L.W.M.A. (L. W M A), Coebergh, J.W.W. (Jan Willem), Schuuring, E. (Ed), Kluin, P.M., and Dongen, J.J.M. (Jacques) van

Abstract

Aims - To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders. Methods - In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR rearrangements was performed. Results - In 98 of 100 histopathologically conclusive cases, Ig/TCR gene results were concordant. In one presumed diffuse large B cell lymphoma (DLCL) and one follicular lymphoma (FL) case no clonality could be detected by SB analysis, or by polymerase chain reaction (PCR) at second stage. In the DLCL, sampling error might have occurred; the FL was revised after an initial diagnosis of reactivity. In many of the histopathologically inconclusive cases Ig/TCR gene SB analysis was helpful, giving support for the histopathological suspicion. However, because of a lack of (clinical) follow up data this could not be confirmed in a few cases. Conclusions - Experienced haematopathologists or a pathologist panel can diagnose malignant versus reactive lesions in most cases without the need for Ig/TCR gene analysis and can select the 5-10% of cases that might benefit from molecular clonality studies.

Published
2001
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204. Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer

Author

Schuuring E, Verhoeven E, van Tinteren H, Jl, Peterse, Nunnink B, Erik Thunnissen, Devilee P, Cj, Cornelisse, Mj, Vijver, and Wj, Mooi

Subjects
Chromosomes, Human, Pair 11, Gene Amplification, Humans, Breast Neoplasms, Female, DNA, Neoplasm, Prognosis, Mastectomy
Abstract

Amplification of the chromosome 11q13 region, which harbors the BCL1 region and the PRAD1, EMS1, HSTF1, and INT2 genes, was found in 36 (16%) of a series of 226 breast carcinomas. In the 153 patients with stage I-IIIa disease who had received no therapy prior to surgery and who were treated with curative intent, 11q13 amplification was associated with the presence of lymph node metastases (P less than 0.002). The presence of an 11q13 amplification was associated with a significantly shorter relapse-free survival (P less than 0.002) and a higher breast cancer-specific mortality (P less than 0.003). Stepwise multivariate analysis showed that, in addition to lymph node status, 11q13 amplification was the best predictor for short survival. Stratified log-rank analysis indicated that, within the group of lymph node-positive breast cancer patients, 11q13 amplification identifies a subgroup at high risk.

Published
1992

206. Limitations of clonality analysis of B cell proliferations using CDR3 polymerase chain reaction.

Author

Hoeve, M.A., Krol, A.D., Philippo, K., Derksen, P.W.B., Veenendaal, R.A., Schuuring, E., Kluin, P., Krieken, J.H.J.M. van, Hoeve, M.A., Krol, A.D., Philippo, K., Derksen, P.W.B., Veenendaal, R.A., Schuuring, E., Kluin, P., and Krieken, J.H.J.M. van

Abstract

Contains fulltext : 184535.pdf (publisher's version ) (Closed access), BACKGROUND/AIMS: Detection of clonal immunoglobulin heavy chain (IgH) rearrangements by the polymerase chain reaction (PCR) is an attractive alternative to Southern blotting in lymphoma diagnostics. However, the advantages and limitations of PCR in clonality analysis are still not fully appreciated. In this study, clonality was analysed by means of PCR, focusing in particular on the sample size requirements when studying extremely small samples of polyclonal and monoclonal lesions. MATERIALS/METHODS: High resolution complementarity determining region 3 (CDR3) PCR was used to investigate the minimum number of cells and the amount of tissue required for the detection of a polyclonal population, both for fresh cells and formalin fixed, paraffin wax embedded tissue. Subsequently, frozen and paraffin wax embedded samples of 76 B cell lymphoproliferative disorders, 43 of which were tested by means of Southern blotting, were analysed to establish the sensitivity of this assay. These specimens included 12 chronic lymphocytic leukaemias (CLLs), nine mantle cell lymphomas (MCLs), 10 follicular lymphomas (FLs), and 45 mucosa associated lymphoid tissue (MALT) lymphomas. The specificity was tested on reactive lymph nodes (n = 19), tonsils (n = 4), peripheral blood lymphocyte fractions (n = 4), and biopsies with gastritis (n = 21). RESULTS: In reactive tissue, 20 ng of high molecular weight DNA derived from 6.5-9 x 10(3) B cells was sufficient to obtain a polyclonal PCR result. With smaller amounts "pseudoclonality" could be induced. When using paraffin wax blocks, undiluted DNA isolated from tonsillar tissue of at least 1 mm2 was necessary to obtain a polyclonal pattern. The sensitivity required to detect clonality in paraffin wax embedded and frozen tissue by PCR for FL (40% and 60%, respectively) was lower than that for MALT lymphomas (60% and 86%, respectively), CLL (78% and 89%, respectively), and MCL (88% and 100%, respectively). PCR specificity was 96% and 100% for frozen

Published
2000

207. A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias.

Author

Bergh, A. von, Emanuel, B., Zelderen-Bhola, S. van, Smetsers, A.F.C.M., Soest, R. van, Stul, M., Vranckx, H., Schuuring, E., Hagemeijer, A., Kluin, P., Bergh, A. von, Emanuel, B., Zelderen-Bhola, S. van, Smetsers, A.F.C.M., Soest, R. van, Stul, M., Vranckx, H., Schuuring, E., Hagemeijer, A., and Kluin, P.

Abstract

Item does not contain fulltext, Reciprocal translocations involving the MLL gene on chromosome band 11q23 have been observed in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In AML, identification of MLL breakpoints is an important prognostic factor. Breakpoints are clustered in an 8 kb DNA fragment (bcr) and can be detected by Southern blotting or fluorescence in situ hybridization (FISH) analysis. Our objective in this study was to design a DNA probe set that enables optimal detection of MLL rearrangements using interphase FISH. Two PAC clones, 217A21 and 167K13, spanning the MLL gene with a minimal overlap in the bcr were isolated and labeled. Twenty-seven AML/ALL patients with cytogenetic 11q23 abnormalities, seven AML/ALL patients without 11q23 abnormalities but MLL rearrangement by Southern blotting, and eight healthy donors were analyzed by FISH. We compared this double-color FISH analysis with FISH using a YAC clone (yB22B2) and with Southern blotting. The PAC probe combination detects an MLL breakpoint in all cases with MLL rearrangement detected by Southern blotting except for cases with a partial tandem duplication detected by reverse transcriptase-polymerase chain reaction (RT-PCR). FISH using the PAC probes also detected MLL breakpoints in four cases with MLL deletions telomeric to the breakpoint that could not be detected by the single probe yB22B2. This new probe set provides a reliable and rapid assay for the diagnosis of AML and ALL patients with MLL/11q23 breakpoints.

Published
2000

211. Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach.

Author

Dekker, T., Borg, S., Hooijer, G., Meijer, S., Wesseling, J., Boers, J., Schuuring, E., Bart, J., Gorp, J., Bult, P., Riemersma, S., Deurzen, C., Sleddens, H., Mesker, W., Kroep, J., Smit, V., and Vijver, M.

Abstract

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks, tissue microarrays were constructed and tested for hormone receptor expression. When a discordant result was found between the local and TMA result, the original testing slide was revised and staining was repeated on a whole-tissue block. Sensitivity and specificity of individual laboratories for testing estrogen receptor expression were high, with an overall sensitivity of 99.7 and 95.4 %, respectively. Overall sensitivity and specificity of progesterone receptor testing were 94.8 and 92.6 %, respectively. Out of 96 discordant cases, 36 cases would have been concordant if the recommended cut-off value of 1 % instead of 10 % was followed. Overall sensitivity and specificity of estrogen and progesterone receptor testing were high among participating laboratories. Continued enrollment of laboratories into quality control schemes is essential for achieving and maintaining the highest standard of care for breast cancer patients. [ABSTRACT FROM AUTHOR]

Published
2015
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212. Frequent alleic imbalance but infrequent microsatellite instability in gastric lymphoma.

Author

Hoeve, M.A., Ferreira Mota, S.C., Schuuring, E., Leeuw, W. de, Chott, A., Meijerink, J.P.P., Kluin, P., Krieken, J.H.J.M. van, Hoeve, M.A., Ferreira Mota, S.C., Schuuring, E., Leeuw, W. de, Chott, A., Meijerink, J.P.P., Kluin, P., and Krieken, J.H.J.M. van

Abstract

Contains fulltext : 184775.pdf (publisher's version ) (Closed access)

Published
1999

213. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy.

Author

Hoeve, M.A., Gisbertz, I.A., Schouten, H.C., Schuuring, E., Bot, F.J., Hermans, J., Hopman, A.H.N., Kluin, P., Arends, J.W., Krieken, J.H.J.M. van, Hoeve, M.A., Gisbertz, I.A., Schouten, H.C., Schuuring, E., Bot, F.J., Hermans, J., Hopman, A.H.N., Kluin, P., Arends, J.W., and Krieken, J.H.J.M. van

Abstract

Contains fulltext : 184780.pdf (publisher's version ) (Closed access)

Published
1999

214. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: — Report of the BIOMED-2 Concerted Action BHM4-CT98-3936

Author

van Krieken, J H J M, primary, Langerak, A W, additional, Macintyre, E A, additional, Kneba, M, additional, Hodges, E, additional, Sanz, R Garcia, additional, Morgan, G J, additional, Parreira, A, additional, Molina, T J, additional, Cabeçadas, J, additional, Gaulard, P, additional, Jasani, B, additional, Garcia, J F, additional, Ott, M, additional, Hannsmann, M L, additional, Berger, F, additional, Hummel, M, additional, Davi, F, additional, Brüggemann, M, additional, Lavender, F L, additional, Schuuring, E, additional, Evans, P A S, additional, White, H, additional, Salles, G, additional, Groenen, P J T A, additional, Gameiro, P, additional, Pott, Ch, additional, and Dongen, J J M van, additional

Published
2006
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215. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936

Author

Evans, P A S, primary, Pott, Ch, additional, Groenen, P J T A, additional, Salles, G, additional, Davi, F, additional, Berger, F, additional, Garcia, J F, additional, van Krieken, J H J M, additional, Pals, S, additional, Kluin, Ph, additional, Schuuring, E, additional, Spaargaren, M, additional, Boone, E, additional, González, D, additional, Martinez, B, additional, Villuendas, R, additional, Gameiro, P, additional, Diss, T C, additional, Mills, K, additional, Morgan, G J, additional, Carter, G I, additional, Milner, B J, additional, Pearson, D, additional, Hummel, M, additional, Jung, W, additional, Ott, M, additional, Canioni, D, additional, Beldjord, K, additional, Bastard, C, additional, Delfau-Larue, M H, additional, van Dongen, J J M, additional, Molina, T J, additional, and Cabeçadas, J, additional

Published
2006
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216. Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936

Author

Langerak, A W, primary, Molina, T J, additional, Lavender, F L, additional, Pearson, D, additional, Flohr, T, additional, Sambade, C, additional, Schuuring, E, additional, Al Saati, T, additional, van Dongen, J J M, additional, and van Krieken, J H J M, additional

Published
2006
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219. Differentiation-dependent expression of provirus-activated int-1 oncogene in clonal cell lines derived from a mouse mammary tumor

Author

Schuuring E, Bj, Leede, Rob Willems, Daams H, van der Valk M, van de Vijver M, van Leeuwen F, Sonnenberg A, Nusse R, and Other departments

Subjects
Mice, Inbred C3H, viruses, Gene Expression, Mammary Neoplasms, Experimental, Cell Differentiation, DNA, Neoplasm, Oncogene Proteins, Viral, Oncogenes, biochemical phenomena, metabolism, and nutrition, Adenocarcinoma, Cell Line, Clone Cells, Mice, Proviruses, Animals
Abstract

The int-1 mammary oncogene is frequently activated by proviral insertion in mouse mammary tumors. To characterize the target cell for the oncogenic action of int-1, we have isolated permanent cell lines with distinct morphologies and differentiation characteristics, starting from a tumor with a rearranged int-1 gene. Polygonal cells had retained many differentiation markers of epithelial cells and produced adenocarcinomas upon transplantation in syngenic mice. Sphere-forming-cuboidal cells are poorly differentiated and produced anaplastic tumors. Cuboidal and elongated cells were negative for epithelial markers. Cuboidal cells were poorly tumorigenic, but elongated cells produced highly malignant sarcoma-like tumors. In all lines, the int-1 gene was identically rearranged due to insertion of proviral DNA of the Mouse Mammary Tumor Virus, but the expression of int-1 varied with the state of differentiation of the cells. Polygonal cells contained relatively high levels of int-1 RNA, which were not influenced by steroid hormones. In the sphere-forming-cuboidal cells, expression of int-1 was low but inducible by dexamethasone. In the cuboidal and elongated cells no expression of int-1 was detectable, showing that the continued expression of int-1 was not required for progression to more malignant cells. By immunoprecipitation, two int-1 protein species, of 42 and 40 kD were identified in polygonal and in sphere-forming-cells but not in the culture media.

Published
1990

220. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

Author

van Dongen, J J M, primary, Langerak, A W, additional, Brüggemann, M, additional, Evans, P A S, additional, Hummel, M, additional, Lavender, F L, additional, Delabesse, E, additional, Davi, F, additional, Schuuring, E, additional, García-Sanz, R, additional, van Krieken, J H J M, additional, Droese, J, additional, González, D, additional, Bastard, C, additional, White, H E, additional, Spaargaren, M, additional, González, M, additional, Parreira, A, additional, Smith, J L, additional, Morgan, G J, additional, Kneba, M, additional, and Macintyre, E A, additional

Published
2003
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221. Fine mapping of the human renal oncocytoma-associated translocation (5;11)(q35;q13) breakpoint

Author

Sinke, R.J., Dijkhuizen, T., Janssen, H.A.P., Olde Weghuis, D.E.M., Merkx, G.F.M., Berg, E. van den, Schuuring, E., Meloni, A.M., Jong, B. de, Geurts van Kessel, A.H.M., Sinke, R.J., Dijkhuizen, T., Janssen, H.A.P., Olde Weghuis, D.E.M., Merkx, G.F.M., Berg, E. van den, Schuuring, E., Meloni, A.M., Jong, B. de, and Geurts van Kessel, A.H.M.

Abstract

Contains fulltext : 25861___.PDF (publisher's version ) (Open Access)

Published
1997

223. Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a phase I–II trial

Author

van Driel, W.J., primary, Ressing, M.E., additional, Kenter, G.G., additional, Brandt, R.M.P., additional, Krul, E.J.T., additional, van Rossum, A.B., additional, Schuuring, E., additional, Offringa, R., additional, Bauknecht, T., additional, Tamm-Hermelink, A., additional, van Dam, P.A., additional, Fleuren, G.J., additional, Kast, W.M., additional, Melief, C.J.M., additional, and Trimbos, J.B., additional

Published
1999
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224. Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998

Author

Gaudray, P., primary, Carle, G.F., additional, Gerhard, D.S., additional, Gessler, M., additional, Mannens, M.M., additional, Athanasiou, M., additional, Bliek, J., additional, Calender, A., additional, Debelenko, L.V., additional, Devignes, M.-D., additional, Evans, G.A., additional, Favier, R., additional, Forbes, S., additional, Gaudray, G., additional, Gawin, B., additional, Gordon, M., additional, Grimmond, S., additional, Grossfeld, P., additional, Harris, J., additional, Hattori, M., additional, Hosoda, F., additional, Hummerich, H., additional, James, M., additional, Kalla, J., additional, Katsanis, N., additional, Little, P., additional, Mattina, T., additional, Negrini, M., additional, Ohki, M., additional, Osborne Lawrence, S., additional, Parente, F., additional, Quincey, D., additional, Raynaud, S., additional, Reid, L., additional, Rethy, L.A., additional, Schuuring, E., additional, Sellar, G., additional, Stilgenbauer, S., additional, Talbot, C., additional, Taschner, P., additional, Thangarajah, T., additional, Tunnacliffe, A., additional, Turc-Carel, C., additional, van Heyningen, V., additional, Weber, G., additional, and Zabel, B., additional

Published
1999
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228. Sensitive and reliable detection of genomic imbalances in human neuroblastomas using comparative genomic hybridisation analysis

Author

Van Gele, M, primary, Van Roy, N, additional, Jauch, A, additional, Laureys, G, additional, Benoit, Y, additional, Schelfhout, V, additional, De Potter, C.R, additional, Brock, P, additional, Uyttebroeck, A, additional, Sciot, R, additional, Schuuring, E, additional, Versteeg, R, additional, and Speleman, F, additional

Published
1997
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233. Involvement of the chromosome 11Q13 region in human cancer

Author

Schuuring, E., primary, Schuuring-Scholtes, E., additional, van Damme, H., additional, van Buuren, V., additional, Brok, H., additional, de Boer, C., additional, Vaandrager, J.W., additional, Kleiverda, K., additional, van Krieken, H., additional, Raap, T., additional, and Kluin, P., additional

Published
1996
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235. Mantle-cell lymphoma: a population-based clinical study.

Author

Velders, G A, primary, Kluin-Nelemans, J C, additional, De Boer, C J, additional, Hermans, J, additional, Noordijk, E M, additional, Schuuring, E, additional, Kramer, M H, additional, Van Deijk, W A, additional, Rahder, J B, additional, Kluin, P M, additional, and Van Krieken, J H, additional

Published
1996
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237. Mantle Cell Lymphoma

Author

Loyson, S.A. J., primary, de Boer, C.J., additional, Schuuring, E., additional, Kluin, Ph. M., additional, and van Krieken, J.H.J.M., additional

Published
1996
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242. FADD expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck.

Author

Pattje, W J, Melchers, L J, Slagter‐Menkema, L, Mastik, M F, Schrijvers, M L, Gibcus, J H, Kluin, P M, Hoegen‐Chouvalova, O, Laan, B F A M, Roodenburg, J L N, Wal, J E, Schuuring, E, and Langendijk, J A

Subjects
MORT1 protein, METASTASIS, CANCER treatment, SQUAMOUS cell carcinoma, HEAD & neck cancer
Abstract

Aims The Fas-associated death domain gene ( FADD) is often overexpressed in squamous cell carcinoma of the head and neck ( HNSCC), and is considered to be a driver gene in amplification of the chromosomal 11q13.3 region. Amplification of 11q13.3 is associated with increased metastasis in HNSCC and breast cancer. The aim of this study was to investigate the association between FADD protein expression in advanced-stage HNSCC and clinicopathological features and outcome. Methods and results Tumour tissues of 177 HNSCC patients uniformly treated with primary surgery and postoperative radiotherapy were collected. FADD expression was assessed on pretreatment tumour biopsies using immunohistochemistry. High FADD expression was detected in 44% of the HNSCC patients. High expression was associated with an increased rate of lymph node metastasis ( P = 0.001) and with a shorter distant metastasis-free interval ( DMFI) ( HR 2.6, 95% CI 1.0-6.7, P = 0.046) when lymph node metastases were present. Conclusions Our data show that an increase in FADD expression is associated with a higher incidence of lymph node metastasis at presentation, and with shorter DMFI when lymph node metastases are present. High FADD expression in the primary tumour could be a useful marker to select patients for systemic treatment strategies that reduce the risk of distant metastases. [ABSTRACT FROM AUTHOR]

Published
2013
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246. A four-gene methylation marker panel as triage test in high-risk human papillomavirus positive patients.

Author

Eijsink, J.J.H., Lendvai, Á., Deregowski, V., Klip, H.G., Verpooten, G., Dehaspe, L., de Bock, G.H., Hollema, H., van Criekinge, W., Schuuring, E., van der Zee, A.G.J., and Wisman, G.B.A.

Abstract

Cervical neoplasia-specific biomarkers, e.g. DNA methylation markers, with high sensitivity and specificity are urgently needed to improve current population-based screening on (pre)malignant cervical neoplasia. We aimed to identify new cervical neoplasia-specific DNA methylation markers and to design and validate a methylation marker panel for triage of high-risk human papillomavirus (hr-HPV) positive patients. First, high-throughput quantitative methylation-specific PCRs (QMSP) on a novel OpenArray™ platform, representing 424 primers of 213 cancer specific methylated genes, were performed on frozen tissue samples from 84 cervical cancer patients and 106 normal cervices. Second, the top 20 discriminating methylation markers were validated by LightCycler® MSP on frozen tissue from 27 cervical cancer patients and 20 normal cervices and ROCs and test characteristics were assessed. Three new methylation markers were identified ( JAM3, EPB41L3 and TERT), which were subsequently combined with C13ORF18 in our four-gene methylation panel. In a third step, our methylation panel detected in cervical scrapings 94% (70/74) of cervical cancers, while in a fourth step 82% (32/39) cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and 65% (44/68) CIN2+ were detected, with 21% positive cases for ≤CIN1 (16/75). Finally, hypothetical scenario analysis showed that primary hr-HPV testing combined with our four-gene methylation panel as a triage test resulted in a higher identification of CIN3 and cervical cancers and a higher percentage of correct referrals compared to hr-HPV testing in combination with conventional cytology. In conclusion, our four-gene methylation panel might provide an alternative triage test after primary hr-HPV testing. [ABSTRACT FROM AUTHOR]

Published
2012
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247. Tumour infiltration depth 4mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma.

Author

Melchers LJ, Schuuring E, van Dijk BA, de Bock GH, Witjes MJ, van der Laan BF, van der Wal JE, and Roodenburg JL

Abstract

Patients with pT1cN0 oral squamous cell carcinomas (OSCC) are generally not treated with a neck dissection (ND). However, in 25% of cN0 patients, nodal metastases become apparent during follow-up. Infiltration depth of the primary tumour has been consistently associated with the presence of nodal metastasis, but proposed cut-off depths for performing a ND vary considerably. The aim of this study was to explore the infiltration depth as predictor for the nodal status and to recommend a cut-off depth for performing a ND. From our database of 351 primary oral carcinomas, we selected all pT1-2 tumours (n=246). Infiltration depth was measured in 212 cases. Neck status was determined by histopathological examination of the dissection specimen, or by at least two years of follow-up. Mean infiltration depth was 5.49mm (95% CI: 4.86-6.12) in the N0 and 8.40mm (95% CI: 7.38-9.43) in the N+ group (p<0.001). cN status, lymphovascular invasion and infiltration depth were the only independent predictors for nodal status in multiple logistic regression. ROC-analysis on pT1cN0 tumours resulted in an optimal cut-off for the prediction of the nodal status at a depth of 4.59mm. This cut-off identified a subgroup of patients at increased risk for nodal metastasis (OR=8.3) and with significantly shorter survival. Tumour infiltration depth is an independent predictor for nodal status in pT1-2 OSCC. In pT1cN0 tumours, a cut-off at 4.59mm results in the best predictive value. We recommend an infiltration depth of 4mm as an indication to perform a neck dissection in pT1cN0 OSCC. [ABSTRACT FROM AUTHOR]

Published
2012

248. Clonality analysis in lymphoproliferative disease using the BIOMED-2 multiplex PCR protocols: experience from the EuroClonality group EQA scheme.

Author

Harris, Susan, Bruggemann, M., Groenen, P., Schuuring, E., Langerak, A., and Hodges, E.

Abstract

The BIOMED-2 primers and PCR protocols for the detection of clonal proliferations in lymphoproliferative disease are well established and are used in many Molecular Pathology laboratories worldwide due to their availability as commercial kits. The kits have made the technical performance of these protocols relatively uncomplicated; however, the technical interpretation is less straightforward, since the reporting of these assays requires knowledge of TCR and BCR gene recombinations, multiple rearrangement patterns and cross-lineage rearrangements. The initial challenge was to first standardise the analysis of these assays across Europe via the EuroClonality group and to issue guidelines for the analysis, interpretation and reporting of the BIOMED-2 assays. This has been achieved and this standardized scoring system will be adopted as an essential part of the BIOMED-2 EuroClonality EQA scheme. [ABSTRACT FROM AUTHOR]

Published
2012
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249. The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer.

Author

Pattje, W. J., Schuuring, E., Mastik, M. F., Slagter-Menkema, L., Schrijvers, M. L., Alessi, S., van der Laan, B. F. A. M., Roodenburg, J. L. N., Langendijk, J. A., and van der Wal, J. E.

Subjects
*SQUAMOUS cell carcinoma, *RADIOTHERAPY, *CANCER patients, *PHOSPHATASES, *MEDICAL radiology, *EPIDERMAL growth factor
Abstract

Background: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is approximately 50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer.Methods: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy.Results: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1-4.6; P=0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2-27.4; P=0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2-6.5; P=0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance.Conclusion: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC. [ABSTRACT FROM AUTHOR]

Published
2010
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