L P Menasce

The University of Manchester, Manchester, ENG, United Kingdom

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Publications (27)86.3 Total impact

  • Journal of clinical pathology 12/2013; · 2.43 Impact Factor
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    ABSTRACT: AIMS: Ying Yang 1 (YY1) is a transcription factor involved in both proliferation and apoptosis. It is prognostic in follicular lymphoma (FL), increased protein levels being associated with favourable outcome. PLK1 is a critical regulator of mitosis, playing a role in spindle formation and in regulation of the G2/M cell cycle checkpoint. PLK1 phosphorylates YY1 at the G2/M checkpoint with activation of YY1 and resultant progression from G2 into mitosis. METHODS: This study aims to investigate possible molecular coexpression and interaction of YY1 with PLK1 in FL using Duolink II in situ proximity ligation assay (PLA) in 51 FL samples in a tissue microarray. RESULTS: Positive PLA signals were present at variable frequency and Kaplan-Meier analysis showed association of signal frequency above the median with unfavourable outcome (p=0.0270). PLA signals were localised to the nuclear edge, with only one signal per cell, suggesting PLK1 and YY1 coexpression at the centrosome. In a minority of cells, two very close PLA signals were present in a single cell, and occasionally, there was a strong ring of semi-confluent fluorescent PLA signals round the nucleus of non-dividing cells, while rarely events were observed in the cytoplasm surrounding dividing cells. CONCLUSIONS: The results confirm association of YY1 and PLK1 with outcome in FL and suggest coexpression at the centrosome. Given the reported interaction of YY1 with PLK1 at the centriole and promotion of cell division at the G2/M checkpoint, the results would concord with the known association of higher proliferation with poor outcome in FL.
    Journal of clinical pathology 06/2013; · 2.43 Impact Factor
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    ABSTRACT: Microarray gene expression profiling of frozen samples has identified Indicator genes predictive outcome in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and there is a now a need to translate these to use in routine clinical material. In order to evaluate the use of Indicator genes as a diagnostic tool in routinely processed formalin fixed paraffin embedded tissue (FFPET), we used a simple, practical polyA PCR based method for analysis of Indicator genes in DLBCL and FL, using parallel FFPET and frozen tissue lymph nodes. PolyA PCR was used to generate polyA cDNAs from 42 archival FFPET lymph nodes and 42 parallel frozen tissue lymph nodes. These polyA cDNAs were assayed by real-time PCR for 35 Indicator genes, identified from previous microarray studies, predictive of outcome in FL and DLBCL, together with housekeeping genes. Housekeeping genes were detectable at high levels in all cases, though the 35 Indicator genes were expressed at lower levels. There was statistically significant difference in gene expression between DLBCL and FL for one of the Indicator genes, HSP27 (p ≤ 0.02). There was no correlation between the Indicator gene expression levels in the FFPET and frozen lymph nodes. The results demonstrate that gene expression in FFPET is altered from that in frozen tissue and that gene expression data from frozen tissue is therefore not transferable for use in FFPET.
    Clinical and experimental pathology 09/2012;
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    ABSTRACT: Some view ultrastructure as key to myofibrosarcoma diagnosis, whereas others argue that electron microscopy is too little used in contemporary practice to be considered an important diagnostic tool. These views are discussed in the context of 10 ultrastructurally confirmed cases of myofibrosarcoma, some occurring at rare sites such as skin and penis. Patient age ranged from 21 to 83 years, with a 6:4 male to female ratio. Size ranged from 2 to 7.5 cm and all had infiltrative margins. Histologically, all consisted of variably cellular fascicles of spindle cells with mild to moderately pleomorphic nuclei, small punctate nucleoli, and eosinophilic cytoplasm. All cases showed α-smooth muscle actin positivity and 2 showed very focal weak positivity for desmin. Ultrastructurally, the tumor cells contained rough endoplasmic reticulum, mainly peripheral smooth-muscle myofilaments, and fibronectin fibrils or fibronexus junctions at the cell surface. The most confident diagnosis of myofibrosarcoma is provided by ultrastructural examination. However, given the right histological appearance, use of a panel of antibodies that includes α-smooth muscle actin, desmin, and h-caldesmon, serves as an acceptable practical way of diagnosing myofibrosarcoma.
    International Journal of Surgical Pathology 07/2012; · 0.76 Impact Factor
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    ABSTRACT: The aim of this study is to report the clinicopathologic characteristics of 3 cases of alveolar rhabdomyosarcoma with neuroendocrine/neuronal differentiation. Specimens of 3 cases of alveolar rhabdomyosarcoma were studied using histologic, immunohistochemical, ultrastructural, and molecular genetic techniques. The patients were a 19-year-old man with metastatic alveolar rhabdomyosarcoma in a groin lymph node, a 16-year-old girl with alveolar rhabdomyosarcoma of the perineum, and a 20-year-old man with recurrent orbital alveolar rhabdomyosarcoma. Microscopically, case 1 was composed of compact sheets of medium to large tumor cells. Cases 2 and 3 were small blue round cell tumors. Cases 1 and 3 were solid throughout, whereas case 2 demonstrated alveolar and solid architecture. By immunohistochemistry, the following markers were positive: desmin (3/3), myogenin (3/3), synaptophysin (3/3), and chromogranin (2/3). Ultrastructurally, sarcomeric filaments were seen in all cases, while neuroendocrine granules were detected only in case 1. PAX:FKHR fusion transcript was identified in case 2, case 3 had a variant PAX3 transcript, and case 1 was negative. The data presented expands the known differentiation of alveolar rhabdomyosarcoma.
    International Journal of Surgical Pathology 08/2008; 17(2):135-41. · 0.76 Impact Factor
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    ABSTRACT: Microarray gene expression profiling studies have demonstrated immune response gene signatures that appear predictive of outcome in follicular lymphoma (FL). However, measurement of these marker genes in routine practice remains difficult. We have therefore investigated the immune response in FL using real-time polymerase chain reaction (PCR) to measure expression levels of 35 candidate Indicator genes, selected from microarray studies, to polyA cDNAs prepared from 60 archived human frozen lymph nodes, in parallel with immunohistochemical analysis for CD3, CD4, CD7, CD8, CD10, CD20, CD21, and CD68. High levels of CCR1, a marker of monocyte activation, were associated with a shorter survival interval, and high levels of CD3 with better survival, while immunohistochemistry demonstrated association of high numbers of CD68(+) macrophages with a shorter survival interval and of high numbers of CD7(+) T cells with a longer survival interval. The results confirm the role of the host immune response in outcome in FL and identify CCR1 as a prognostic indicator and marker of an immune switch between macrophages and a T cell-dominant response. They demonstrate the utility of polyA DNA and real-time PCR for measurement of gene signatures and the applicability of using this type of "molecular block" in clinical practice.
    Blood 06/2008; 111(9):4764-70. · 9.78 Impact Factor
  • British Journal of Haematology 05/2008; 141(1):124-6. · 4.94 Impact Factor
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    ABSTRACT: Recent microarray gene expression profiling studies have identified gene signatures predictive of outcome, so-called "indicator" genes, for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, measurement of these genes in routine practice remains difficult. We applied real-time polymerase chain reaction (PCR) to polyA cDNAs prepared from 106 archived human frozen lymph nodes (63 of FL, 25 of DLBCL, 10 reactive lymph nodes, and cases with paired samples of FL [4] and subsequent DLBCL [4]). Reverse transcription and polyA reverse transcriptase (RT)-PCR was performed, and resultant cDNA was probed by real-time PCR for 36 candidate indicator genes, selected from microarray studies. Nine genes showed statistically significant different expression between FL and DLBCL, including cyclin B, COL3A1, NPM3, H731, PRKCB1, OVGL, ZFPC150, HLA-DQ-a, and XPB. Of these, cyclin B, NPM3, and COL3A1 were higher in DLBCL. Six genes showed statistically significant higher expression in the neoplastic nodes compared with reactive nodes, namely PRKCB1, BCL-6, EAR2, ZFX, cyclin B, YY1. High levels of YY.1 were associated with a shorter survival interval in both FL and DLBCL. The method is simple, sensitive, and robust, facilitating routine use and may be used as a platform for clinical measurement of prognostic gene signatures.
    Blood 06/2007; 109(9):3922-8. · 9.78 Impact Factor
  • Histopathology 05/2006; 48(5):621-3. · 2.86 Impact Factor
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    ABSTRACT: We report 2 cases of partially regressed malignant melanoma in which the brisk lymphocytic response closely resembled mycosis fungoides in 1 case and nodular sclerosing Hodgkin lymphoma in the other. Striking epidermotropism was present in both cases. The lymphocytes were predominantly of T8 cytotoxic subtype, and oligoclonal T-cell expansion was detected in 1 of the cases. The scanty residual melanoma cells were highlighted with HMB45 and S100 protein. We highlight the features of regression in melanoma that may lead to an erroneous diagnosis of lymphoma and discuss the finding of oligoclonal T-cell expansion in regressed melanocytic lesions.
    International Journal of Surgical Pathology 08/2005; 13(3):281-4. · 0.76 Impact Factor
  • L P Menasce, B Eyden
    Histopathology 04/2005; 46(3):342-4. · 2.86 Impact Factor
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    ABSTRACT: To describe the clinicopathological and immunohistochemical features of cutaneous malignant melanomas with a pure or mixed small-cell pattern in 11 adult patients, and to discuss the diagnostic difficulties encountered. Haematoxylin and eosin-stained sections of each case of cutaneous small-cell malignant melanoma, together with locally recurrent skin lesions and, where available, metastatic deposits, were re-examined. Available immunohistochemical sections were evaluated. Clinical follow-up data were obtained in each case. One patient presented with metastatic disease, the others presented with cutaneous lesions. Suggested initial diagnoses included malignant melanoma, non-Hodgkin's lymphoma, Merkel cell carcinoma and sarcoma. All the tumours were in the vertical growth phase. Nine had a junctional component, often inconspicuous. The lesions showed either a pure small-cell pattern or a mixed pattern with more conventional areas. In one case, there was colonization of a basal cell carcinoma by invasive malignant melanoma. Variable retention of small-cell morphology in local recurrences and metastases was observed, although in some cases more typically pleomorphic cells were present. In the cases tested, there was strong immunostaining for S100 protein and NKI-C3, and variable immunostaining for HMB45 and Melan-A. Non-melanocytic markers were negative. The possibility of a small-cell malignant melanoma should be considered in the assessment of cutaneous and non-cutaneous small-cell neoplasms. The correct diagnosis requires careful evaluation for junctional activity, melanin production and the use of a panel of melanocytic markers.
    Histopathology 03/2002; 40(2):187-95. · 2.86 Impact Factor
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    ABSTRACT: Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.
    Ultrastructural Pathology 01/2002; 26(5):269-85. · 0.98 Impact Factor
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    ABSTRACT: To bring to wider attention this uncommon, poorly understood entity which may closely resemble, clinically and morphologically, follicular lymphoma. We report three cases of follicular lymphoid hyperplasia of the hard palate and oral mucosa which caused diagnostic difficulties for the referring pathologists. The clinicopathological features are described and integrated into a review of the 16 previously recorded cases. The condition most commonly presents as a slowly growing mass situated in the posterior hard palate but may present with multicentric oral lesions and lymphadenopathy. Morphologically, it is characterized by a dense follicular lymphoid infiltrate within the lamina propria which may show the classical features of benign reactive hyperplasia, but not uncommonly, indistinct germinal centres, ill-defined mantles and a lack of tingible-body macrophages are features which may lead to an erroneous diagnosis of follicular lymphoma. Follicular lymphoid hyperplasia of the palate is a poorly recognized entity which is frequently confused with follicular lymphoma. Awareness of the entity combined with the use of immunohistochemistry for immunoglobulin light chains and bcl-2 protein allows a correct diagnosis to be made avoiding extensive investigation and aggressive treatment to the patient.
    Histopathology 11/2001; 39(4):353-8. · 2.86 Impact Factor
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    ABSTRACT: Peri-vascular matrices having a finely textured granular substructure have been identified in 27 human lesions: these were mostly malignancies but included benign tumours and reactive processes. The matrices were defined as stromal components surrounding endothelium and pericytes, and lying between vessels and adjacent lesional cells. They were identified as having a finely textured, uniform and moderately dense substructure, and differed from a conventional basal lamina expected at these sites by the absence of the typical lamina densa/lamina lucida configuration. By light microscope immunohistochemistry, vessels stained positively for laminin and collagen IV, two of the main proteins characterising a conventional basal lamina. The present observations emphasise the following. 1) The proteins laminin and collagen IV can be found in peri-vascular locations which have a finely textured granular substructure, and which have clearly defined ultrastructural differences from a conventional basal lamina. 2) While conventional light microscope immunohistochemistry demonstrates the presence and cellular location of proteins, electron microscopy is helpful for giving information on their physical organisation. 3) Peri-vascular granular matrices have a widespread distribution in malignant tumours but also exist in benign tumours and reactive lesions. This paper briefly discusses the possible functions of these matrices as modulators of cell biological processes.
    Journal of submicroscopic cytology and pathology 11/2000; 32(4):515-23.
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    ABSTRACT: We report a case of metastatic malignant melanoma in an inguinal lymph node, expressing ganglioneuroblastic differentiation. This was characterized by the presence of discrete nests and islands of large ganglion cells with abundant cytoplasm and eccentric nuclei with prominent nucleoli admixed with smaller primitive neuroblasts. The cells were separated by pale pink fibrillar material representing neuritic cell processes. These foci of ganglioneuroblastoma were seen over a background of an otherwise typical metastatic epithelioid, focally melanotic, malignant melanoma. Immunohistochemistry showed positivity for neurofilament, synaptophysin, chromogranin, vasoactive intestinal peptide, and glial fibrillary acidic protein in the areas with ganglioneuroblastic differentiation, but not in the melanocytic component. Conversely, HMB45 positivity was expressed by the melanocytic cells only. S-100 protein and Melan-A, a putative melanocytic marker, showed positivity in both melanocytic and ganglioneuroblastic components. Ultrastructurally, neuritic cell processes and dense core neurosecretory granules were identified in the ganglionic and neuroblastic cells. A subsequent nodal metastasis in the same region showed focal neuroblastic differentiation without the ganglionic element. No evidence of neuronal or ganglionic differentiation was seen in the primary skin melanoma.
    American Journal of Surgical Pathology 06/1999; 23(5):582-8. · 4.87 Impact Factor
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    ABSTRACT: To describe the clinicopathological and immunophenotypic features of 26 cases of extra-medullary myeloid tumour (EMMT)/granulocytic sarcoma, which remains poorly recognized and is frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist. Haematoxylin and eosin (H & E) sections of 26 cases of EMMT were re-examined. Immunostains for myeloperoxidase, lysozyme, neutrophil elastase, LCA, CD79a, CD20, CD43, CD45RO, CD3, CD30, CD15, CD68, MAC387, VS38C, MIC2, and the Leder stain for naphthol-ASD-chloroacetate esterase were performed on all cases. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the notes of the patients where available. In the 10 cases with known myeloproliferative disease, the initial diagnosis was correct in 10 whereas all cases presenting with EMMT without a previous history of myeloproliferative disorder had an initial incorrect diagnosis. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma. The morphology of the tumours varied from well differentiated which included all stages of myeloid differentiation to poorly differentiated or blastic showing little or no evidence of myeloid differentiation. The proportion of positive cells for each stain varied. Chloroacetate esterase, myeloperoxidase and CD15 stained a large proportion of cells of the majority of the well differentiated tumours and a smaller proportion of the poorly differentiated/blastic tumours with very focal staining of some of the cases. Lysozyme and CD43 were the most sensitive of the markers staining a large proportion of cells of the majority of the tumours in both groups. Neutrophil elastase was the least sensitive of the markers of myeloid differentiation. CD79a, CD20, CD3 and CD30 were negative in all cases. CD43 was positive in all cases. CD68 stained a substantial number of cells in the majority of tumours. A smaller proportion of the tumours stained with MAC387. Four of the tumours showed positivity for MIC2. One tumour was positive for VS38C. This series documents continuing difficulties in the diagnosis of EMMT. Even well differentiated tumours are frequently mistakenly diagnosed as malignant lymphomas when they present without any history of antecedent myeloproliferative disorder. Careful evaluation of morphology for evidence of myeloid differentiation and a high index of suspicion when confronted with a less differentiated neoplasm are required to avoid this important diagnostic error. We suggest that a panel which includes chloroacetate-esterase, myeloperoxidase, lysozyme and CD43, together with other B- and T-lineage markers, in particular CD79a and CD3 should be used to confirm the diagnosis.
    Histopathology 05/1999; 34(5):391-8. · 2.86 Impact Factor
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    ABSTRACT: To document the clinical, morphological and immunohistochemical features of two cases of primary mucosal melanoma with osteocartilaginous differentiation. Two cases of mucosal melanoma with cartilage and bone formation are reported, one arising in the vagina of a 79-year-old woman and one in the oral cavity of a 67-year-old man. The vaginal melanoma exhibited only cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both bone and cartilage formation and was remarkable for its multifocality, long history not associated with metastases and its lengthy manifestation of dual morphologies: some of the tumours were typical in situ/invasive melanotic melanomas whilst the others were composed of amelanotic spindle and epithelioid cells with osteocartilaginous tissue. One of the lesions exhibited in situ and invasive melanoma with transition to an osteogenic tumour in places. The patient also developed nonosteogenic malignant melanomas in the nasal cavity and nasopharynx. Malignant melanomas showing foci of osteocartilaginous differentiation are extremely rare with only 18 cases reported. Primary mucosal malignant melanomas of vagina and oral cavity showing osteocartilaginous differentiation have not previously been documented. Primary vaginal melanoma with cartilaginous differentiation must be distinguished from primary malignant mixed Müllerian tumour whilst malignant change in a pleomorphic adenoma, sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are included in the differential diagnosis of primary oral mucosal melanomas with osteocartilaginous differentiation. In this context, immunohistochemistry using antibodies to cytokeratin, S100 protein and MIC2 is of value.
    Histopathology 10/1998; 33(3):255-60. · 2.86 Impact Factor
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    ABSTRACT: To describe the clinicopathological and immunophenotypic features of 25 cases of Kikuchi-Fujimoto disease (K-F), which remains a poorly recognized entity and is still frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist. Haematoxylin and eosin sections of 27 lymph node biopsies were re-examined. Immunostains for B-lymphocytes, T-lymphocytes and macrophages were performed. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the patients' notes where available. The suggested initial diagnoses are discussed. The lymph nodes showed a necrotizing process characterized by patchy or confluent areas of necrosis associated with karyorrhexis and absence or paucity of granulocytes. This was associated with a proliferation of large blastic cells consisting of a mixture of T-lymphocytes and histiocytes. Fragmentation of the biopsy was a frequent feature. The diagnosis of K-F was suggested by the referring pathologist in three cases only. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma. This series documents continuing difficulties in the diagnosis of Kikuchi-Fujimoto disease in the UK and emphasizes that cases are still being mistakenly diagnosed as malignant lymphomas. The diagnosis of Kikuchi-Fujimoto disease merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young women presenting with cervical lymphadenopathy.
    Histopathology 10/1998; 33(3):248-54. · 2.86 Impact Factor
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    ABSTRACT: Adenocarcinoma of the rete testis is a rare testicular tumour, which often presents late, with metastatic disease present in a significant proportion of patients. We record the clinicopathological findings in a man who presented with an apparently localized testicular tumour. He however went on to develop a rapidly progressive local recurrence and metastatic disease, despite primary radiotherapy. Detailed immunohistochemical examination was performed and we record positivity of this tumour for the recently developed markers HBME1 and thrombomodulin.
    Clinical Oncology 02/1998; 10(6):401-3. · 2.86 Impact Factor

Publication Stats

566 Citations
86.30 Total Impact Points

Institutions

  • 1993–2013
    • The University of Manchester
      • • School of Biomedicine
      • • Manchester Medical School
      • • School of Psychological Sciences
      Manchester, ENG, United Kingdom
  • 2001–2005
    • The Christie NHS Foundation Trust
      • Clinical Oncology
      Manchester, England, United Kingdom