bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas
Authors: Holm R , Skovlund E , Skomedal H , Flørenes V A , Tanum G 
Published: March 2003

Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas Aims: p21 and p27 protein expression were examined in a comparatively large series of patients with squamous cell carcinoma of the anal canal and compared with clinical and histopathological data (tumour stage, nodal status and differentiation). Methods and results: We analysed the expression of p21 and p27 protein in 94 anal carcinomas by immunohistochemistry. Nuclear p21 and p27 staining were detected in 71% (67/94) and 75% (71/94) of the cases, respectively. There was no significant association between p27 staining and tumour stage, nodal status or overall survival. We observed that negative p21 immunoreactivity was significantly associated with poorly differentiated anal carcinomas. Furthermore, a shorter overall survival for patients with no p21 protein expression was seen. Conclusions: Our data indicate that p21 levels, but not p27 expression, may be a useful predictor of survival in patients with anal carcinomas.
Differential immunoreactivity of melanocytic lesions of the conjunctiva
Authors: Sharara N A , Alexander R A , Luthert P J , Hungerford J L , Cree I A 
Published: March 2003

Differential immunoreactivity of melanocytic lesions of the conjunctiva Aims: To evaluate the expression of S100NKI/C3 and HMB45 antigens in melanocytic lesions of the conjunctiva and the ability of HMB45 to aid assessment of neoplasia. Methods and results: Stored formalin‐fixed specimens of conjunctival melanomas and primary acquired melanosis were considered as participants and conjunctival naevi and racial melanosis as controls. Ninety‐seven conjunctival melanocytic lesions were analysed using formalin‐fixed paraffin‐embedded material. These included 20 melanomas arising in the context of primary acquired melanosis (PAM), 22 melanomas arising without evidence of pre‐existing PAM, seven cases of PAM with atypia, nine cases of PAM with no atypia, 35 conjunctival naevi and four cases of racial melanosis. S100 and NKI/C3 were similarly expressed in all lesions, with at least one of these markers positive in 100% of the lesions examined. HMB45 was expressed in 72.7% of primary melanomas and 85% of melanomas in the context of PAM; 42.8% of PAM with atypia expressed HMB45 while it was expressed in 11.1% of PAM without atypia and 8.5% of naevi. Racial melanosis cases did not express HMB45. S100 and NKI/C3 were expressed to a similar extent in all groups. Conclusions: S100 and NKI/C3 are useful markers to assess the extent of melanocytic lesions in the conjunctiva. HMB45 immunoreactivity can act as a useful aid to histopathology for the distinction of benign from malignant conjunctival lesions, particularly in the context of primary acquired melanosis.
Splenic littoral cell haemangioendothelioma: a new low‐grade variant of malignant littoral cell tumour
Authors: Ben‐Izhak O , Bejar J , Ben‐Eliezer S , Vlodavsky E 
Published: March 2003

Splenic littoral cell haemangioendothelioma: a new low‐grade variant of malignant littoral cell tumour Aims: Littoral cell angioma is a recently described splenic vascular tumour of splenic sinus lining cells. Almost all cases of splenic littoral cell tumours hitherto described were benign. Methods and results: A splenic littoral cell tumour recurred 8 years after splenectomy, with an abdominal mass and multiple liver metastases, resulting in the patient’s death. Histologically, the original splenic tumour showed solid areas with small necrotic foci in addition to large areas of typical littoral cell angioma. The recurrent tumours showed increased solid architecture and slightly increased nuclear atypia. The tumours showed an immunohistochemical profile positive for factor VIII, CD31, CD68, cathepsin D, and CD21 and negative for CD34 and CD8, consistent with the immunophenotype of classic littoral cell angioma. Ki67 index in the recurrent tumours was higher than in the primary tumour. Conclusions: The mildly atypical, but not frankly malignant, histological features as well as the protracted clinical course support definition of the tumour as ‘littoral cell haemangioendothelioma’. Low rate of Ki67 staining and diploid DNA histogram with low S‐phase fraction of the tumours are in accordance with a low‐grade malignancy. Literature review revealed two other cases of littoral cell tumours with disseminated disease that may be other examples of littoral cell haemangioendothelioma. Littoral cell haemangioendothelioma should be distinguished from the overtly malignant splenic angiosarcomas, of which a few may show splenic lining cell differentiation with some immunohistochemical features of littoral cells. Due to difficulties in predicting biological behaviour based on histological features of splenic littoral cell tumours, a long‐term follow‐up for these patients, especially for those with atypical histology, is recommended.
Pseudo‐partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles
Authors: Paradinas F J , Sebire N J , Fisher R A , Rees H C , Foskett M , Seckl M J , Newlands E S 
Published: March 2003

Pseudo‐partial moles: placental stem vessel hydrops and the association with Beckwith–Wiedemann syndrome and complete moles Aims: To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann syndrome. Methods and results: We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as ‘large’. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified. Conclusions: This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith–Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.
Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases
Authors: Kurian K M , Al‐Nafussi A 
Published: March 2003

Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases Aims: To analyse the clinical and pathological features with long‐term follow‐up of a series of 12 cases of sarcomatoid carcinoma of the breast. Methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacent in‐situ carcinoma/atypical epithelial proliferation. The mean age of the patients was 61 years with a median of 64 and range 46–82 years. The mean size of the tumour was 52 mm (range 22–100 mm). None of the patients had distant metastasis at presentation and only one case had local lymph node metastasis which had a carcinomatous appearance. Five women were still alive after a minimum 12‐year follow‐up period. Four patients died of their disease (three with lung metastasis only and one with lung and bone metastases), one died of carcinoma of the cervix and two patients were lost to follow‐up. Pathologically, four cases (33.3%) had no or almost undetectable epithelial structures by light microscopy, i.e. ‘monophasic sarcomatoid carcinoma’. The remaining cases revealed varying proportions of both epithelial and mesenchymal elements, i.e. ‘biphasic sarcomatoid carcinoma’. Of the epithelial component, six (50%) tumours had predominantly carcinoma of no special type, one lobular and one tubular carcinoma. The mesenchymal component was fibromatosis/nodular fasciitis‐like, malignant fibrous histiocytoma‐like (MFH), osteosarcoma‐like and fibrosarcoma‐like in five (42%), four (33%), two (17%) and one (8%) tumours, respectively. In 3/4 monophasic tumours, the mesenchymal component was of a low‐grade fibromatosis/nodular fasciitis type. In 6/12 (50%) of the cases there was associated in‐situ atypical epithelial proliferation (five ductal carcinoma in situ (DCIS) and one atypical ductal hyperplasia). Conclusions: From this small series it appears that sarcomatoid carcinoma is an uncommon tumour, which is large in size and tends to lack local or distant metastasis at presentation. Pathologists should be alert to the presence of the bland monophasic sarcomatoid carcinoma which has a pure mesenchymal appearance on light microscopy, but epithelial components demonstrated by cytokeratin immunohistochemistry. These showed metastases on long‐term follow‐up, similar to other histological patterns of sarcomatoid carcinoma.
Accessory cell tumour: a clinicopathological study of 16 aggressive tumours containing EBV‐positive Hodgkin and Reed–Sternberg‐like giant cells
Authors: Shimazaki K , Ohshima K , Haraoka S , Suzumiya J , Nakamura N , Kikuchi M 
Published: March 2003

Accessory cell tumour: a clinicopathological study of 16 aggressive tumours containing EBV‐positive Hodgkin and Reed–Sternberg‐like giant cells Aims: Lymph nodes contain non‐lymphoid accessory cells including follicular dendritic cells and interdigitating dendritic cells. Functionally, these cells belong to the category of immune accessory cells involved in antigen presentation to B or T‐lymphocytes. Neoplastic proliferation of these cells is very uncommon. We present here the clinicopathological features of 16 cases of accessory cell tumour. Methods and results: We performed electron microscopic and immunohistochemical examinations, and used in‐situ hybridization for EBV‐encoded RNA (ISH‐EBV) to detect the EBV genome in 11 cases, and Southern blot analysis to assess EBV clonality in two cases. Tumour cells were composed of oval‐to‐spindle cells arranged in diffuse, vague storiform, fascicular and sometimes whorled patterns in a background of small lymphocytes. In all cases, binucleated or multinucleated Hodgkin and Reed–Sternberg‐like giant cells were encountered. Staining for CD68 was positive in all cases. CD21, CD35, Ki‐M4p, Ki‐FDC1p, and S100 exhibited variable reactivity. ISH‐EBV yielded positive labelling in seven of 11 cases, of which five exhibited EBV only in Hodgkin and Reed–Sternberg‐like giant cells. Southern blot analysis showed clonality of EBV terminal repeats (EBV‐TR) in the two cases examined. Electron microscopic examination showed that many of the tumour cells had numerous interwoven long villous cell processes connected by occasional desmosomes. Many tumours were very refractory to chemotherapy and radiation, with a few exceptions, and half of the cases classified initially as stage IV. A short survival time, of 10 months or less, was observed in seven of 16 patients. Conclusions: Our study identified more aggressive behaviour of accessory cell tumours. Our results suggest that EBV may potentially induce activation of accessory cells to form Hodgkin and Reed–Sternberg‐like giant cells, which correspond with poor prognosis.
Matrix metalloproteinase‐2 expression correlates with morphological and immunohistochemical epithelial characteristics in synovial sarcoma
Authors: Saito T , Oda Y , Sakamoto A , Tamiya S , Iwamoto Y , Tsuneyoshi M 
Published: March 2003

Matrix metalloproteinase‐2 expression correlates with morphological and immunohistochemical epithelial characteristics in synovial sarcoma Aims: Synovial sarcoma is a unique mesenchymal tumour characterized by the presence of epithelial differentiation, although the mechanism involved in the epithelial morphology is still unclear. The aim of this study was to evaluate the function of matrix metalloproteinase‐2 (MMP‐2) in synovial sarcoma, in order to assess whether MMP‐2 expression plays an important role in epithelial differentiation, or whether it contributes to a poor clinical outcome. Methods and results: Immunohistochemical stainings for MMP‐2, cytokeratins (CKs) 7, 8, 18 and 19, and E‐cadherin were performed for 58 (44 monophasic and 14 biphasic) cases of synovial sarcoma, and we compared the expression of these proteins with the histological and clinical findings. MMP‐2 and E‐cadherin expression was observed in 43 cases (74.1%) and in 18 cases (31.0%), respectively. Expression of these proteins was preferentially observed in the glandular components of biphasic tumours or the epithelioid areas of monophasic tumours. Statistically significant correlations were recognized between MMP‐2 expression and E‐cadherin expression of biphasic subtype. Moreover, there were statistically significant correlations between monophasic tumours with epithelioid areas and MMP‐2 expression or E‐cadherin expression. MMP‐2 expression was correlated with epithelial differentiation as assessed by CK immunoreactivity. The expression of MMP‐2 did not affect the overall survival rate in synovial sarcoma. Conclusions: MMP‐2 expression seemed to have an important role to play in the epithelial differentiation of tumour cells in synovial sarcoma, through remodelling of the extracellular matrix and by changing the cytoskeletal interaction between the extracellular matrix and tumour cells.
PTEN is not altered in sporadic vestibular schwannomas
Authors: Mawrin C , Kirches E , Boltze C , Dietzmann K 
Published: March 2003

PTEN is not altered in sporadic vestibular schwannomas Aims: To investigate the role of the tumour suppressor gene PTEN in the tumorigenesis and growth of sporadic vestibular schwannomas, and to characterize the cellular distribution of the PTEN protein in relation to the MIB‐1 proliferation index in these tumour. Methods and results: Immunoexpression of the PTEN protein was observed within the neoplastic Schwann cells in 21 out of 30 sporadic schwannomas examined (70%). PTEN expression was consistently stronger in Antoni A areas than in Antoni B areas. High levels of PTEN immmunoexpression in schwannomas were associated with an increased MIB‐1 labelling index. Occasionally, vascular endothelial cells also showed PTEN immunoreaction. By polymerase chain reaction‐single strand conformation polymorphism screening, no mutations were found in the complete protein coding region of the PTEN gene. Conclusions: The PTEN tumour suppressor gene is expressed in the majority of sporadic schwannomas. The maintained expression of the PTEN protein, together with the lack of detectable mutations in this gene, suggests that the function of the PTEN tumour suppressor gene is not altered in sporadic vestibular schwannomas.
Unusual intraparenchymal growth patterns of malignant pleural mesothelioma
Authors: Nind N R , Attanoos R L , Gibbs A R 
Published: March 2003

Aims:  Malignant pleural mesothelioma is known to mimic morphologically a number of diverse reactive and neoplastic conditions. We describe three unusual intraparenchymal growth patterns of malignant mesothelioma seen in a series of 200 malignant pleural mesotheliomas. The diagnostic pitfalls associated with these findings are described and their potential medico‐legal implications are highlighted.Methods and results:  The study group comprised 200 malignant pleural mesotheliomas. In each case diagnosis was morphologically confirmed with ancillary immunohistochemistry using a broad panel of both mesothelial and epithelial markers. The patterns of intraparenchymal growth were documented and grouped as: direct subpleural; lymphangitic; and other. The 200 malignant pleural mesotheliomas comprised 118 epithelioid, 57 biphasic and 25 sarcomatoid, subtyped according to the WHO classification. Direct subpleural invasion was seen in 42 cases, lymphangitic spread in 27 cases. Other less well‐defined intraparenchymal patterns included three sarcomatoid subtype malignant mesotheliomas exhibiting an intra‐alveolar growth pattern mimicking epithelioid haemangioendothelioma. One epithelioid subtype malignant mesothelioma contained an intraparenchymal tumour nodule microscopically comprising lepidic spread of neoplastic cells over maintained alveolar structures mimicking bronchioloalveolar carcinoma. One epithelioid subtype malignant mesothelioma morphologically had areas in which alveoli were distended by discohesive epithelioid neoplastic cells with no interstitial invasion. The appearances mimicked desquamative interstitial pneumonia. Immunohistochemistry played an important role in the definitive diagnosis of each unusual parenchymal tumour deposit. In 126 malignant mesotheliomas no invasion of the subjacent lung parenchyma was identified.Conclusions:  An awareness of the unusual parenchymal growth pattern in malignant mesothelioma is important to prevent misdiagnosis of other entities. In the medico‐legal setting, the presence of epithelioid haemangioendothelioma or bronchioloalveolar carcinoma (in the absence of asbestosis) may be deemed to impact upon the patient's anticipated life expectancy and thereby would decrease the compensation settlement.
TCR‐α chain‐like molecule is involved in the mechanism of antigen‐non‐specific suppression of a ubiquitin‐like protein
Authors: Nakamura M. , Tsunematsu T. , Tanigawa Y. 
Published: March 2003

Although existence of suppressor T cells is a controversial issue in cellular immunology, several lines of evidence indicate that T‐cell‐receptor α‐chain (TCR‐α) is a critical component of suppressor factors produced by these cells. Monoclonal non‐specific suppressor factor (MNSF), a lymphokine produced by murine T‐cell hybridoma, possesses pleiotrophic antigen‐non‐specific suppressive functions. Recently, we have shown that the 70 000‐MW MNSF comprises an 8000‐MW ubiquitin‐like polypeptide and other subunit(s). Here we report that the 8000‐MW ubiquitin homologue is associated with an intracellular TCR‐α (but not TCR‐β) ‐like molecule and released from the cells. The affinity eluates obtained from the culture supernatants of E17 cells and concanavalin A (Con A)‐activated splenocytes with anti‐TCR‐α monoclonal antibody (mAb) showed an antigen‐non‐specific, major histocompatibility complex (MHC)‐non‐restricted suppression. Immunoblot analysis demonstrated that anti‐TCR‐α, but not anti‐TCR‐β, mAb recognizes native 70 000‐MW MNSF. In addition, we found the dissociation of the 8000‐MW polypeptide from the 62 000‐MW TCR‐α cross‐reactive protein by hydrolase which cleaves isopeptide bonds. Thus the covalent attachment of ubiquitin‐like protein(s) may be involved in the underlying mechanism of suppressor T‐cells and TCR‐α‐like molecule(s) might be a main link between antigen‐specific and non‐specific suppression.hNSF, human non‐specific suppressor factor MNSF, monoclonal non‐specific suppressor factor Ubi‐L, ubiquitin‐like moiety.
Analysis of immunoglobulin E VH transcripts in a bronchial biopsy of an asthmatic patient confirms bias towards VH5, and indicates local clonal expansion, somatic mutation and isotype switch events
Authors: Snow R. E. , Djukanovic R. , Stevenson F. K. 
Published: March 2003

SummaryImmunoglobulin E (IgE)‐dependent mechanisms play a pivotal role in mediating allergic disease. Previously, VH‐Cε transcripts from blood or spleen of atopic asthmatics have been analysed for VH gene usage and patterns of somatic mutation. An over‐representation of the minor VH5 family has been observed, consistent with a superantigen drive. As local mucosal events in IgE production may be more significant in the disease process, we have analysed VH‐Cε transcripts from a bronchial biopsy of a patient with severe asthma. VH5 predominance was confirmed with 10 of 30 unique clones derived from this family. Repeated sequences, some with intraclonal variation, revealed clonal expansion and continuing mutational activity at the site. Unexpectedly, three unmutated VH‐Cε sequences were found, indicating that isotype switching to IgE can occur without mutation. Detection of a sister clone with extensive mutations was again consistent with local mutational activity. Evidence for local isotype switching was obtained by identification of clonally related immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin E (IgE) sequences. However, in contrast to findings in blood, no IgG4 transcripts clonally related to IgE were detected, suggesting that the balance between synthesis of IgG4 and IgE may differ between systemic and local sites. These data confirm a VH5 bias in IgE, and support the concept that IgE‐synthesizing B cells arise via local differentiation.
Dimerization of major histocompatibility complex class I on the surface of THP‐1 cells stimulates the expression of inducible nitric oxide synthase and subsequent nitric oxide release
Authors: Bottley G. , Fernández N. 
Published: March 2003

SummaryWe show that dimerization of major histocompatibility complex (MHC) class I on a human monocytic cell line, THP‐1, induces nitric oxide (NO) synthesis. Cells cultured in the presence of a human MHC class I‐specific monoclonal antibody produced significant amounts of NO after 72 hr. Reverse transcription–polymerase chain reaction and flow cytometry analysis revealed that the cells synthesized detectable levels of inducible NO synthase mRNA and protein. These effects were not seen after treatment with monovalent Fab fragments or Fc fragments of the same antibody, or after treatment with a control antibody. These data show a link between innate and acquired immune mechanisms mediated by NO and MHC class I.
Cyclooxygenase‐independent inhibition of dendritic cell maturation by aspirin
Authors: Matasić R. , Dietz A. B. , Vuk‐Pavlović S. 
Published: March 2003

SummaryWhen immature human myeloid dendritic cells were differentiated in vitro in the presence of aspirin, they were unable to stimulate T‐cell proliferation. Aspirin and its major metabolite salicylate changed the surface marker phenotype of dendritic cells. The drugs particularly suppressed the levels of CD83 and the secreted p40 unit of interleukin‐12 (IL‐12), both markers of mature dendritic cells; 50% inhibitory concentration (IC50) values were 2·5 m
m, a concentration more than 100 times greater than the concentration at mid‐point inhibition (ID50) value for inhibition of prostaglandin synthesis. Concomitantly, the levels of CD14, a marker of monocytes/macrophages, increased above the levels found in immature dendritic cells. Cyclooxygenase inhibitors ketoprofen, indomethacin and NS‐398 had no effect at concentrations more than a thousand‐fold higher than their IC50 values. The effects were independent of the presence of prostaglandin E2 in the medium. Salicylates suppressed activation of the nuclear transcription factor κB, which regulates dendritic cell differentiation, but their effects on mature dendritic cells were negligible. Hence, aspirin inhibits dendritic cell function by inhibiting their terminal differentiation at concentrations achieved in the blood of patients chronically treated with high‐dose aspirin.