bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical alveolar hyperplasia: Relationship with pulmonary adenocarcinoma, p53, and c‐erbB‐2 expression
Authors: Kerr Keith M. , Carey Francis A. , King George , Lamb David 
Published: June 2005

AbstractAtypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well‐recognized progenitor lesion. Epidemiological, morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1–13 lesions per case, mean 3·5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case‐load of 285 adenocarcinoma‐bearing lungs, the AAH incidence was 8·8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c‐erbB‐2 (NCL‐CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty‐nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c‐erbB‐2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c‐erbB‐2 staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant.
Incidence of latent infection of Epstein–Barr virus in lung cancers—an analysis of EBER1 expression in lung cancers by in situ hybridization
Authors: Kasai Kiyoshi , Sato Yuichi , Kameya Toru , Inoue Hayato , Yoshimura Hirokuni , Kon Shinichiro , Kikuchi Kokichi 
Published: June 2005

AbstractTo evaluate the presence of Epstein–Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV‐encoded small nuclear RNA‐1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC‐LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma‐like undifferentiated carcinoma (LELC) of the lung, the PDSCC‐LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a 32P‐labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1‐positive cases, the genome was found to be positive in the five cases with EBER1‐positive staining, including the PDSCC‐LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV‐associated lung cancers are not restricted to the typical LELC type.
Prognostication of astrocytoma patient survival by Ki‐67 (MIB‐1), PCNA, and S‐phase fraction using archival paraffin‐embedded samples
Authors: Sallinen Pauli K. , Haapasalo Hannu K. , Visakorpi Tapio , Helén Pauli T. , Rantala Immo S. , Isola Jorma J. , Helin Heikki J. 
Published: June 2005

AbstractThe prognostic power of three proliferation estimation methods, Ki‐67 (MIB‐1) and PCNA immunohistochemistry, and flow cytometry (S‐phase and S+G2/M fractions, respectively), were evaluated in 50 cases of astrocytoma. Each proliferation index showed a strong association with the grade of malignancy (grades I‐IV). The MIB‐1 labelling index (LI) provided additional information, as it could be used for the discrimination of grade II and grade III astrocytomas (P=0·0357). All three proliferation estimation methods also had strong prognostic potential (MIB‐1 LI: P<0·0001; PCNA Li: P<0·0001; S‐phase: P=0·0004; S+G2/M: P=0·0124). According to the receiver operating characteristics (ROC) curve, the MIB‐1 LI showed generally the best sensitivity and specificity in placing the patients correctly into groups of survivors and non‐survivors, which was further confirmed in the multivariate analysis. Only 4 per cent of the patients having high MIB‐1 scores (>15·3 per cent) were alive after 2‐years' follow‐up. In contrast, 72 per cent of patients with tumours of low proliferation activity survived. It appears that Ki‐67 (MIB‐1) immunolabelling using archival paraffin‐embedded samples is of value in predicting prognosis in astrocytic tumours.
Characterization of a subtype of primary osteoclastoma: Extracellular calcium but not calcitonin inhibits aggressive HLA‐DR‐positive osteoclastoma possessing ‘functional’ calcitonin receptors
Authors: Rathod Hersha , Malcolm Archibald J. , Gillespie James I. , Berry Vanita , Pooley Joseph , Piggott Nigel H. , Datta Harish K. 
Published: June 2005

AbstractWe report here a case of primary osteoclastoma that despite possessing HLA‐DR‐positive status and ‘functional’ calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell‐mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura‐2AM based microspectrofluorimetric assays, the presence of the ‘functional’ calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA‐DR‐positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors.
Intrahepatic expression of hepatitis C virus antigens in chronic liver disease
Authors: Nouri‐Aria Kayhan T. , Sallie Richard , Mizokami Masashi , Portmann Bernard C. , Williams Roger 
Published: June 2005

AbstractLocalization of hepatitis C virus (HCV) antigens was studied in fresh frozen and formalin‐fixed, paraffinembedded liver tissue by immunoperoxidase using monoclonal antibodies to nucleocapsid protein and polyclonal human immunoglobulin G purified from plasma containing antibodies to structural and non‐structural antigens of hepatitis C virus. The results observed using monoclonal antibody to HCV core were similar to those of polyclonal IgG against HCV antigens in the majority of cases and both correlated well with HCV status as defined by ‘nested’ polymerase chain reaction. HCV antigens were detected in both hepatocytes and mononuclear cells. Using polyclonal human IgG, a small proportion of biliary epithelial cells were also positive in 6/29 patients. In most of the specimens examined, relatively few cells (1–5 per cent) were found to be positive for HCV antigens. The cryostat sections, using polyclonal IgG against HCV antigens, exhibited greater immunohistochemical staining, suggesting that the fixation and processing of the tissue may be a major factor in the conservation and the outcome of HCV antigen(s) findings. However, the results using monoclonal antibodies may reflect the specificity of antigen expression.
Is the carbohydrate sialosyl‐Tn a marker for altered, non‐malignant activity in squamous epithelium in the head and neck region?
Authors: Bryne M. , Gravdahl C. , Koppang H. S. , Kjærheim Å. , Dabelsteen E. 
Published: June 2005

AbstractCell surface carbohydrates are involved in many cell functions such as cellular differentiation, adhesion, and invasion. A carbohydrate, sialosyl‐Tn (STn), is expressed in many human carcinomas but generally not in normal epithelia. In the oral mucosa, however, STn had recently been observed on basal cell in some lesions with epithelial hyperplasia and dysplasia. The aim of this study was to carry out a systematic investigation of STn expression on epithelial basal cells in hyperplastic, ‘borderline’ malignant, and malignant head and neck lesions, to see if the expression of STn is associated specifically with hyperplastic conditions. Using the primary monoclonal antibody TKH2, normal controls did not reveal STn. STn was detected on probably post‐mitotic basal cells in hyperplastic head and neck lesions and on basal cells adjacent to cancers, but not within the carcinomas. A Ki67 antibody reacted with basal cells in other locations. The most highly differentiated lesions, such as focal epithelial hyperplasia and verrucous hyperplasia, revealed a high percentage (86 per cent in both cases) of STn reactivity. The least‐differentiated verrucous carcinomas (VCs) and keratoacanthomas (KAs) did not express STn, in contrast to the highly differentiated VCs and KAs. These findings indicate that STn‐negative cases may have a greater malignant potential that the STn‐positive cases. In conclusion, STn expressed on basal cells is possibly a marker for non‐malignant conditions with altered basal cell activity and for highly differentiated verrucous carcinomas.
Human papillomavirus DNA in oesophageal carcinomas in South Africa
Authors: Cooper Kumarasen , Taylor Louise , Govind Sanjay 
Published: June 2005

AbstractUsing morphological criteria, the presence of human papillomavirus (HPV) in oesophageal carcinomas has been inferred in patients from Finland and South Africa. However, studies to demonstrate the viral antigen in tissue sections of these tumours have proved disappointing. This study investigates 48 archival oesophageal carcinoma biopsies from South Africa for the presence of HPV DNA using non‐isotopic in situ hybridization (NISH) with HPV DNA probes to HPV 6, 11, 16, 18, 31, and 33. HPV DNA sequences were detected in 25/48 (52 per cent) oesophageal cancers. HPV 16 was present in 84 per cent of the HPV‐positive cancers. A NISH type 2 signal pattern (punctate/dot) was present in all HPV‐positive tumours. This signal pattern was previously shown to represent integrated HPV DNA within host chromosome. Integrated HPV DNA in oesophageal cancers has also been demonstrated in patients from China and Japan. In addition, the prevalence of HPV DNA in oesophageal cancers from high‐risk countries like South Africa (52 per cent) and China (49 per cent) would appear to be consistent.
17q allele loss is associated with lymph node metastasis in locally aggressive human colorectal cancer
Authors: Purdie Colin A. , Piris Juan , Bird Colin C. , Wyllie Andrew H. 
Published: June 2005

AbstractA consecutive series of 87 colorectal tumours were studied for loss of a polymorphic probe on chromosome 17q and of the 64 informative cases, 13 (20 per cent) showed loss of heterozygosity (LOH). Examples of LOH were found in carcinomas of all stages and in a large non‐invasive adenoma. There was no correlation between 17q LOH and patient age, sex, standard clinicopathological variables (differentiation and nature of tumour margin), DNA ploidy, or tumour site, nor was 17q LOH associated with 17p LOH defined at four loci adjacent to p53. However, comparison of Dukes' B and C carcinomas revealed that tumours which had metastasized to regional lymph nodes at the time of primary surgery were significantly more likely to have lost this 17q allele. Clinical follow‐up of this cohort of patients showed no significant difference in survival between patients whose tumours had lost or retained 17q. Thus, we conclude that 17q allele loss is associated with lymph node metastasis in locally aggressive colorectal tumours but probably not with blood‐borne metastasis.
Chromosome 1 aneusomy, identified by interphase cytogenetics, in mammographically detected ductal carcinoma in situ of the breast
Authors: Harrison Michele , Magee Hilary M. , O'loughlin John , Gorey Thomas F. , Dervan Peter A. 
Published: June 2005

AbstractBecause of the relative rarity of ductal carcinoma in situ (DCIS) in the premammographic screening era, the unavailability of adequate fresh tissue for culture, and the lack of cytogenetic expertise in most pathology departments, there is little information on karyotypic abnormalities in DCIS. The purpose of this study was to investigate the frequency of chromosome 1 aneusomy in DCIS, using interphase cytogenetic techniques, and to correlate the findings with nuclear grade. Twenty‐one cases of DCIS, identified in a mammographically screened population, were studied by in situ hybridization. Chromosome 1 numbers were identified in interphase nucler in conventional histology sections, using a specific centromeric probe (pUC 1.77). In each case, 100 tumour nuclei were compared with 100 normal nuclei. Eighteen of 21 (86 per cent) cases were aneusomic for chromosome 2. This included 15 of 16 (94 per cent) pure comedo or predominantly comedo DCIS. Fifteen of 16 (94 per cent) DCIS with grade 3 nuclei and 3 of 5 (60 per cent) cases with grade 2 nuclei were aneusomic. One case with grade 3 nuclei (a comedo carcinoma) was negative. We conclude that chromosome 1 aneusomy precedes invasion and is a relatively consistent occurrence in those DCIS with high nuclear grade.
Upregulation of integrin expression in benign vulvar warts
Authors: Williams A. T. , Sexton C. J. , Hanna N. F. , Leigh I. M. 
Published: June 2005

AbstractBenign anogenital warts demonstrate features both of hyperproliferation and of aberrant differentation associated with human papillomavirus (HPV) infection. The expression of integrins has been examined in normal vulvar epithelium and benign vulvar warts to determine whether HPV infection is associated with changes in integrin expression, either during terminal differentiation or among the proliferating cell population. The expression of integrins in normal vulvar epithelium was similar to that seen in the epidermis, with little expression of α1 and expression of α2, α3, and β1 at the periphery of basal cells. In vulvar wart epithelium, α1 was not significantly expressed, but upregulation of α2, α3, and β1 was seen at the periphery of cells throughout the basal and spinous layers. In addition, α2 staining was greater at foci along the basal layer of normal vulva, whilst such heterogeneity was not detected in wart sections. Expression of β4 and αv was confined to the basal and lateral aspects of normal basal cells, but expressed at the periphery of basal cells and to a lesser extent in epibasal and spinous layers of warts. The observed differences in integrin expression are consistent with those reported in other hyperproliferative epithelia.
Mononuclear cell thyroiditis in rats with graft‐versus‐host disease
Authors: Fujiwara Kouji , Peszkowski Michael J. , Larsson Åke , Yamasaki Akira , Toda Shuji , Watanabe Teruo 
Published: June 2005

AbstractRats with graft‐versus‐host disease (GVHD), induced by injecting spleen cells of parental strain rats (Brown Norway) into non‐irradiated (Brown Norway × Lewis) F1 hybrid rats, develop thyroiditis. This is characterized by mononuclear cell infiltration with destruction of the epithelium and a significant reduction in serum thyroid hormone levels. Immunohistochemically, the mononuclear cells consisted mainly of CD8‐positive cells and macrophages. These findings provide evidence that the thyroid gland can now be enumerated as one of the target organs during GVHD. The CD8‐positive cells may serve as important effector cells in lesion development, either by direct cytotoxicity or by supporting the cytotoxic potential of macrophages.
Low incidence of mbr bcl‐2/JH fusion genes in Hodgkin's disease
Authors: Kneba Michael , Eick Stefan , Herbst Hermann , Pott Christiane , Bolz Ingrid , Dallenbach Friederike , Hiddemann Wolfgang , Stein Harald 
Published: June 2005

AbstractLymph node biopsies from 140 cases of Hodgkin's disease (HD) and from 30 non‐malignant lesions were screened for the presence of t(14;18) translocations involving the major breakpoint region (mbr) of the bcl‐2 gene and the joining region (J)H of the immunoglobulin heavy chain gene, using a polymerase chain reaction (PCR) assay with subsequent nucleotide sequencing of amplified bcl‐2/JH junctional regions. Expression of the bcl‐2 protein within the Hodgkin and Reed‐Sternberg (HRS) cells was investigated in 86 cases of HD by immunohistochemistry on cryostat or paraffin sections. Although bcl‐2 expression could be found in a proportion of neoplastic cells in up to one‐third of HD cases, the frequency of t(14;18) gene fusions detected by PCR was low. We identified such gene fusions in only 3 out of 140 (2 per cent) HD cases, one biopsy of which presented with four clonally distinct bcl‐2/JH sequences. No t(14;18) was found in any of 30 reactive lymph node lesions. All fusion gene sequences were unique regarding the localization of the chromosome 14 and 18 breakpoints and the extranucleotide N‐insertions. None of these gene fusions conformed to t(14;18) breakpoint sequences previously characterized in our laboratories. Our findings point to a mere coincidence in some cases of HD lesions and cells carrying a t(14;18) in the same biopsy and argue against a significant role of bcl‐2 in the pathogenesis of HD.
Immunohistochemical localization of thrombomodulin in normal human skin and skin tumours
Authors: Jackson D. E. , Mitchell C. A. , Bird P. , Salem H. H. , Hayman J. A. 
Published: June 2005

AbstractThrombomodulin (TM) expression has been investigated in sections of normal human skin, in cultured normal human keratinocytes, and in a variety of skin tumours. TM was present in squamous epithelial cells in the spinous layer of normal epidermis and in the outer root sheath of hair follicles, but was absent in the cells of the basal layer. It appeared to be predominantly localized to the cell membrane and the intercellular bridges in these areas. Cultured normal human keratinocytes demonstrated functionally active constitutive TM expression on their cell surface. Immunoperoxidase staining of skin tumours using anti‐human TM antibodies demonstrated a typical cell membrane positivity in tumours with squamous or hair follicle differentiation. Basal cell carcinomas showed TM expression only in areas where incomplete squamoid metaplasia occurred. Sweat gland tumours and lesions of the melanogenic system failed to express TM. The localization of TM by immunostaining in various benign and malignant skin tumours typically correlated with their normal skin element of origin. The physiological significance of TM expression in the epidermis is currently undefined.
An evaluation of the staining of lymphomas and normal tissues by the rabbit polyclonal antibody to protein gene product 9.5 following non‐enzymatic retrieval of antigen
Authors: Langlois N. E. I. , King G. , Herriot R. , Thompson W. D. 
Published: June 2005

AbstractWe have previously described the staining of normal follicle centre lymphoid cells by the rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5), following an antigen unmasking step employing heat pretreatment. Applying this finding to a range of lymphomas to determine whether this phenomenon could have a role in identifying lymphomas of follicle centre origin revealed no relationship between type or grade of lymphoma and staining of neoplastic cells. Testing a range of normal tissues following antigen retrieval displayed increased sensitivity and a greater range of tissue positivity. Immunoblots of gel electrophoresed tonsil and brain extract were performed. Although subjecting these blots to antigen unmasking increased sensitivity, no novel epitopes, in terms of additional bands, appeared. This suggested that antibody specificity remained unaltered.
p53 gene point mutations in relation to p53 nuclear protein accumulation in colorectal cancers
Authors: Costa Aurora , Marasca Roberto , Valentinis Barbara , Savarino Marco , Faranda Alessandra , Silvestrini Rosella , Torelli Giuseppe 
Published: June 2005

AbstractIt is known that structural alterations of the p53 tumour suppressor gene cause malignant transformation and tumour progression in colorectal mucosa. In this study, 38 colorectal cancers were analysed for mutations detected in the p53 gene by single‐strand conformational polymorphism and DNA sequence analysis, and the results were compared with p53 protein expression detected by immunohistochemistry. A very strict association (P<0·0001) was found between genetic alterations and protein accumulation, as detected by the PAb 1801 monoclonal antibody. p53 expression and gene mutations were more frequent in rectal than in colonic cancers. No relation was observed with Dukes' stage, even though most of the mutations were at exon 7 in Dukes' A–B cancers and almost all mutations at exon 8 were observed in Dukes' C–D cancers. DNA ploidy was not generally associated with p53 protein expression or gene mutations. However, 83 per cent of cases with exon 5 and 6 mutations were diploid or near‐diploid and 71 per cent of cases with mutations at exons 7 and 8 were aneuploid. Tumours with p53 gene mutations at exon 5 had a higher median [3H]thymidine labelling index (17 per cent) than those with mutations at exons 6, 7, and 8 (11·8 per cent).
An evaluation of the cell cycle‐associated monoclonal antibody Ki‐S1 as a prognostic factor in primary invasive adenocarcinoma of the breast
Authors: Morris E. S. , Elston C. W. , Bell J. A. , Galea M. , Blamey R. W. , Ellis I. O. 
Published: June 2005

AbstractImmunohistochemical staining with the novel monoclonal antibody Ki‐S1, believed to recognize a cell cycle‐associated antigen, was investigated in 110 cases of invasive carcinoma of the breast. Immunoreactivity indices were compared with disease‐free interval (DFI), overall survival, and a series of other prognostic indicators. Significant positive correlations were found between the percentage of strongly positive immunoreactive nuclei and tumour size, histological grade and type, vascular invasion, and mitotic count. A significant negative correlation was found with age. No significant correlation was found with either DFI or overall survival. Although a correlation with mitotic count does imply that the Ki‐S1 antigen is cell cycle‐associated to some extent, Ki‐S1 does not appear to be a useful prognostic factor in human breast carcinoma.
Lectin‐binding properties of the antral and body surface mucosa in the human stomach—are the differences relevant for Helicobacter pylori affinity?
Authors: Baczako Karl , Kühl Philippa , Malfertheiner Peter 
Published: June 2005

AbstractBiopsy specimens from histologically normal human gastric mucosa were examined histochemically with the use of lectins. Significant differences were found in the glycoconjugate patterns of the surface mucous cells between the body and the corresponding antrum. Two lectins (Ulex europaeus agglutinin I and Ricinus communis agglutinin I) specific for fucose and galactose residues stained the apical membrane and the intracellular (perinuclear) region of the antral mucosa more strongly than those of the body (P<0·04). Body and antral biopsies from patients with Helicobacter pylori‐positive chronic active gastritis were also studied, but the lectin patterns of Helicobacter pylori‐infected body and antrum did not differ. On comparing these chronically infected gastric biopsies with normal antral mucosa, however, significant changes could be seen with the fucose‐binding lectin as well as with two other lectins (succinylated concanavalin A and peanut agglutinin).These differences could have been induced directly by bacterial virulence factors or could be due to non‐specific reactions to the inflammatory process.