bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of tumor‐associated 90k‐antigen in human breast cancer: No correlation with prognosis and response to first‐line therapy with tamoxifen
Authors: Foekens John A. , Klun Jan G. M. , Natoli Clara , Van Putten Wim L. J. , Stefano Pia Di , Look Maxime P. , Portengen Henk , Lacobelli Stefano 
Published: February 2007

AbstractIt has been shown that a 90‐kDa protein (90K), with an as yet unknown function, is expressed in the majority of human breast‐cancer tissues. In addition, the serum level of this 90K antigen is elevated in a certain proportion of breast‐cancer patients, and high serum levels are associated with a poor overall survival. It was therefore of interest to determine whether levels of 90K in tumor tissues could be used as a prognostic variable in breast cancer. In the present study, the levels of 90K in primary breast tumor cytosols were studied with respect to the length of relapse‐free or overall survival in 547 patients (median follow‐up, 81.4 months), and the relationship with response to first‐line tamoxifen therapy and the length of progression‐free survival in 184 patients with recurrent disease (median follow‐up, 59.8 months). 90K levels in tumor cytosols were determined with an immunoradiometric assay. The cytosolic contents of 90K were not significantly correlated with age, menopausal status, tumor size, nodal status or differentiation grade. On the other hand, the levels of 90K were positively correlated with those of cytosolic estrogen receptor, progesterone receptor, urokinase‐type plasminogen activator, its inhibitor PAI‐I, cathepsin D and PS2. The cytosolic tumor level of 90K was not associated with the rate of relapse or death in primary breast cancer, nor with response to first‐line therapy with tamoxifen or the length of progression‐free survival in recurrent disease. © 1995 Wiley‐Liss, Inc.
c‐crbB2 gene amplification and protein expression in ovarian epithelial tumors: Evaluation of their respective prognostic significance by multivariate analysis
Authors: Fajac Anne , Benard Jean , Lhomme Catherine , Rey Annie , Duvillard Pierre , Rochards France , Bernaudin Jean‐Francois , Riou Guy 
Published: February 2007

Abstractc‐erbB2 gene amplification or over‐expression has been reported in ovarian cancer, but their prognostic value remains conflicting. To investigate the respective prognostic significance of c‐erbB2 gene amplification and protein over‐expression, tumor samples were obtained from 65 patients with ovarian adenocarcinoma (9 FIGO stage I, 7 stage ll, 38 stage III and 11 stage IV) followed up for a median period of 71 months. c‐erbB2 gene amplification (>2.5 a.u.) was detected in 9/65 (14%) adenocarcinomas and in none of 5 benign and 8 borderline ovarian epithelial tumors also analyzed. Specimens from 52 of the 65 adenocarcinomas were available for immunohistochemi‐cal analysis. c‐erbB2 protein expression was observed in 23/52 (44%) adenocarcinomas. No correlation was found between c‐erbB2 gene copy number and protein expression. There was no correlation of c‐erbB2 gene copy number or protein expression with any of the clinico‐pathological factors analyzed (i.e., GIGO stage, histological type, histological grade and residual tumor). On univariate analysis, c‐erbB2 gene amplification was associated with poorer survival (p = 0.04). However, in the multivariate analysis of clinico‐pathological factors and c‐erbB2 gene copy number, c‐erbB2 gene amplification did not retain any independent prognostic significance (p = 0.19). No significant survival difference was found between patients with and without c‐erbB2 protein over‐expression in univariate or multivariate analyses. Therefore, neither c‐erbB2 gene amplification nor c‐erbB2 protein over‐expression appears to be a significant prognostic marker in patients with ovarian carcinoma. © 1995 Wiley‐Liss, Inc.
Sequential p53 mutation analysis of pre‐invasive and invasive head and neck squamous carcinoma
Authors: El‐Naggar Adel K. , Lai Syeling , Luna Mario A. , Zhou Xiao‐Dong , Weber Randal S. , Goepfert Helmuth , Batsakis John G. 
Published: February 2007

AbstractSingle‐stranded conformation polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non‐invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis‐sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non‐sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non‐invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non‐invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development. © 1995 Wiley‐Liss, Inc.
Detection of TP53 gene mutation in human meningiomas: A study using immunohistochemistry, polymerase chain reaction/single‐strand conformation polymorphism and dna sequencing techniques on paraffin‐embedded samples
Authors: Wang Jia‐Lun , Zhang Zhi‐Jia , Hartman Magdalena , Smits Anja , Westermark Bengt , Muhr Carin , Nistér Monica 
Published: February 2007

AbstractMutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin‐embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas. © 1995 Wiley‐Liss, Inc.
Microsatellite instability in multiple gastric cancers
Authors: Nakashima Hideaki , Honda Masayuki , Inoue Hiroshi , Shibuta Kenji , Arinaga Shinya , Era Shoichi , Ueo Hiroaki , Mori Masaki , Akiyoshi Tsuyoshi 
Published: February 2007

AbstractTo better elucidate the role of genetic instability in the development of gastric cancer, microsatellite alterations were examined in a total of 30 gastric cancers that developed in 14 Japanese patients with multiple gastric cancers, which are considered to have possibly occurred under the same genetic background and in the same microenvironment of the stomach. Microsatellite instability (MSI) in multiple gastric cancers was recognized in 11 out of 14 cases (78.5%) and in 16 out of 30 cancers (53.3%). Eight out of 11 cases showing MSI exhibited a heterogeneity of microsatellite alterations. The incidence of microsatellite instability in the multiple gastric cancers cases was significantly higher than that in the solitary gastric cancer cases reported previously (20.8%: 5 out of 24 cases). These results suggested that (1) genetic instability plays a more important role in the development of multiple gastric cancers than in that of solitary gastric cancer and (2) the heterogeneity of MSI in multiple gastric cancers may not be a rare event, although the significance of the heterogeneity could not be clarified. © 1995 Wiley‐Liss, Inc.
Retinoic acid receptors and retinoid binding proteins in endometrial adenocarcinoma: Differential expression of cellular retinoid binding proteins in endometrioid tumours
Authors: Siddiqui Nadeem A. , Thomas Eric J. , Dunlop William , Redfern Christopher P. F. 
Published: February 2007

AbstractRetinoic acid is apparently required for the normal differentiation of reproductive epithelium. Cellular abnormalities in retinoid homeostasis could be a factor in the development of endometrial malignancy. We have thus investigated the expression of nuclear retinoic acid receptors (RARs and RXRs) and cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) in endometrial adenocarcinoma of the endometrioid histological subtype. Ten grade 1, 11 grade 2 and 10 grade 3 tumour samples, as well as 4 samples of severe atypical precan‐cerous endometrial hyperplasia, were studied. No significant difference in expression of RAR‐β was detected in tumour samples compared with normal epithelial cells. RAR‐γ was significantly elevated in grade 1 and 2 carcinomas, but this may be due to greater stromal cell involvement in these lower grade tumours. There was significant elevation of CRBP 1 mRNA in tumour samples. Furthermore, although undetectable in normal endometrial epithelium, CRABP 1 was expressed in 3/11 grade 2 and 9/10 grade 3 carcinomas, with expression being significantly higher where the primary tumour had invaded more than 50% of the total myometrial thickness. Analysis of 2 epithelial‐like endometrial adenocarcinoma cell lines supported the idea that CRABP 1 expression is characteristic of poorly differentiated endometrial adenocarcinoma. Our data suggest that alterations in mechanisms of retinoid homeostasis are a feature of endometrial adenocarcinoma and may contribute to the severity of disease. © 1995 Wiley‐Liss, Inc.
Expression of 2 variant forms of fibroblast growth factor receptor 1 in human breast
Authors: Luqmani Yunus A. , Mortimer Caroline , Yiangou Constantinos , Johnston Caroline L. , Bansal Gurpal S. , Sinnett Dudley , Law Matthew , Charles Coombes R. 
Published: February 2007

AbstractThe expression of variant mRNAs encoding isoforms of fibroblast growth factor receptor (FGFR) 1 with either 2 or 3 Ig‐like loops in the extracellular domain was investigated in human breast tissues and cell lines using a polymerase chain reaction amplification method. Almost all tissues contained both forms of FGFR1, but cancers (n = 137) had a significantly lower proportion of the transcript that encoded the full 3‐loop form compared with non‐malignant biopsies (n = 34). This was confirmed using microdissected populations of normal and cancerous cells from frozen tissue sections. A high ratio of the 2‐to 3‐loop form was found to be predictive of reduced relapsefree survival. In both groups, however, the predominant form of FGFR1 was that encoding the 2‐loop receptor. Cell lines derived from a variety of tissues, including breast, also co‐expressed both variants of FGFR1, suggesting their presence within the same cell type. Again, there was a similar preponderance of the shorter isoform. Our results were confirmed at the protein level, where out of 5 cancers analysed 4 expressed more of the 2‐loop form than the 3‐loop form. Our findings suggest that cells may normally simultaneously express several splice variants of FGFR1, and aberrant expression or a change in their relative amounts (i.e., in malignancy) could contribute to modified responses to either autocrine or paracrine factors. © 1995 Wiley‐Liss, Inc.
ERBB2 gene amplification detected by fluorescent differential polymerase chain reaction in paraffin‐embedded breast carcinoma tissues
Authors: An Han‐Xiang , Niederacher Dieter , Beckmann Matthias W. , Göhring Uwe‐Jochen , Scharl Anton , Picard Frauke , van Roeyen Claudiavan , Schnürch Hans‐Georg , Bender Hans G. 
Published: February 2007

AbstractFor quantificative determination of ERBB2 gene amplification in archival human carcinoma specimens we have developed a rapid, non‐radioactive approach, which is based on the differential polymerase chain reaction (PCR) and fluorescent DNA technique. Sequences from the ERBB2 gene and from a singlecopy reference gene were amplified simultaneously by PCR, in which one of each primer pair was fluorescently labelled. PCR products were separated by polyacrylamide gel electrophoresis in an automated DNA sequencer and directly quantified after laser activation and emission scanning using appropriate software. This fluorescent differential polymerase chain reaction (fd‐PCR) method was used for quantificative determination of ERBB2 gene amplification in 195 formalin‐fixed, paraffin‐embedded breast carcinoma tissues. ERBB2 gene amplification was found in 52 (26%) of these tumors and correlated significantly with tumor size, absence of estrogen receptor (ER) and pS2 expression, but not with absence of progesterone receptor (PR) or presence of epidermal growth factor receptor (EGF‐R) expression, lymph‐node metastases or grading. In univariate analysis, ERBB2 gene amplification showed no significant correlation with clinical outcome, either in the whole population or in the subgroup defined by positive axillary lymph‐node metastases. However, within the node‐negative subgroup, patients with ERBB2 gene amplification had significantly decreased relapse‐free survival and overall survival (p < 0.05). The fd‐PCR assay is a valuable tool for determination of amplification of ERBB2 gene as well as further oncogenes. In this way, more detailed information about individual tumor biology may be acquired by a routine assay. © 1995 Wiley‐Liss, Inc.
Expression of the MAGE gene family in human head‐and‐neck squamous‐cell carcinomas
Authors: Eura Masao , Ogi Kojiro , Chikamatsu Kazuaki , Lee Kang Dac , Nakano Koji , Masuyama Keisuke , Itoh Kyogo , Ishikawa Takeru 
Published: February 2007

AbstractThe MAGE genes encode certain tumor‐associated antigens recognized by cytotoxic T lymphocytes. We investigated the expression of the MAGE‐1, ‐2, ‐3, ‐4, ‐41 and ‐6 genes in 88 head‐and‐neck squamous‐cell carcinomas (83 fresh tumor samples and 5 cell lines), using a reverse‐transcription‐polymerase‐chain‐reaction assay, followed by dot‐blot hybridization with sequence‐specific oligonucleotides and/or restriction‐enzyme‐pattern analysis. The MAGE‐1, ‐2, ‐3, ‐4, ‐41 and ‐6 genes were expressed at the mRNA level in 27, 34, 36, 22, 16 and 35, respectively, of 83 fresh tumor samples. At least one of these genes was expressed in 59 of the 83 samples. Neither non‐tumor inflammatory cells nor normal tissues were positive for these genes. The MAGE‐1 gene was expressed relatively frequently in SCC of the oropharynx, hypopharynx and maxillary sinus, but at lower rates in SCC of the larynx and of the tongue and oral cavity. MAGE‐1 was frequently expressed in poorly differentiated SCC, somewhat less frequently in moderately differentiated SCC, and only infrequently in well‐differentiated SCC. The expression levels of the other MAGE genes also varied with the anatomic site as well as the degree of differentiation. Our results suggest that specific immunotherapy against MAGE gene products may be useful for patients with head‐and‐neck carcinomas. © 1995 Wiley‐Liss, Inc.
Expression of autocrine motility factor receptor in human esophageal squamous cell carcinoma
Authors: Maruyama Kentaro , Watanabe Hideomi , Shiozaki Hitoshi , Takayama Takuya , Gofuku Junji , Yano Hiroshi , Inoue Masatoshi , Tamura Shigeyuki , Raz Avraham , Monden Morito 
Published: February 2007

AbstractAutocrine motility factor and its receptor (gp78) have been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected gp78 expression in buffered‐formalin‐fixed, paraffin‐embedded sections of esophageal squamous cell carcinomas using an anti‐gp78 monoclonal antibody (MAb), 3F3A, and examined the relationship between gp78 expression and clinicopathological and prognostic factors. In 55 of 101 (54%) patients, gp78 was detected in the tumor cells. The frequency of gp78‐positive expression was significantly associated with tumor size, infiltrative growth, depth of invasion and lymph node metastasis. The cumulative survival rate of patients with gp78 was significantly lower than that of patients without gp78. Our results suggest that autocrine motility factor receptor (gp78) expression could be a useful biomarker for malignancy grading and prognosis in patients with esophageal squamous cell carcinoma. © 1995 Wiley‐Liss, Inc.
Microsatellite instability in oral cancer
Authors: Ishwad Chandramohan S. , Ferrell Robert E. , Rossie Karch M. , Appel Billy N. , Johnson Jonas T. , Myers Eugene N. , Law John C. , Srivastava S. , Gollin Susanne M. 
Published: February 2007

AbstractGeneralized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the Somatic loss of DNA mismatch repair capability. Germ‐line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non‐polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50‐74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30‐58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors. © 1995 Wiley‐Liss, Inc.
Activation of the precursor of gelatinase A/72 kda type IV collagenase/MMP‐2 in lung carcinomas correlates with the expression of membrane‐type matrix metalloproteinase (MT‐MMP) and with lymph node metastasis
Authors: Tokuraku Masato , Sato Hiroshi , Murakami Sinya , Okada Yasunori , Watanabe Yoh , Seiki Motoharu 
Published: February 2007

AbstractWe have identified a novel membrane‐type matrix metalloproteinase (MT‐MMP) expressed on the cell surface and inducing activation of pro‐gelatinase A in vitro. In this study, we further examined the possibility that MT‐MMP is the activator of pro‐gelatinase A in tumors as well as in vitro. Expression of MT‐MMP mRNA was analyzed by Northern blotting in 58 cases of human lung carcinomas. MT‐MMP mRNA expression was increased in tumor tissues compared with adjacent normal tissues. The ratio of MT‐MMP mRNA levels in tumor/normal tissues (T/N ratio) was 3.19 ± 1.62 in 29 cases of adenocarcinoma, 3.09 ± 1.44 in 24 cases of squamous cell carcinoma, 4.40 ± 0.47 in 3 cases of large cell carcinoma and 3.63 ± 2.11 in 2 cases of small cell carcinoma, respectively. Activated gelatinase A, as detected by gelatin zymography, was also predominant in tumors compared with normal tissue counterparts, though the difference in mRNA levels was not significant. The activation ratio of gelatinase A in tumor vs. normal tissues correlated well with that of MT‐MMP mRNA expression and with lymph node metastases. Our findings suggest that MT‐MMP is indeed the tumor‐specific activator of pro‐gelatinase A in lung carcinomas and is important to initiate invasion of basement membranes. © 1995 Wiley‐Liss, Inc.
Microsatellite instability and alterations in the HMSH2 gene in human ovarian cancer
Authors: Fujita M. , Enomoto T. , Yoshino K. , Nomura T. , Buzard G. S. , Inoue M. , Okudaira Y. 
Published: February 2007

AbstractThe role of the replication error‐positive (RER+) phenotype in the development of specific subtypes of sporadic ovarian carcinomas was examined by screening for the presence of microsatellite instability (MI) in 47 tumors. The overall frequency of ovarian MI was 17% only. However, MI occurred in 50% of the ovarian endometrioid‐type tumors, which was significantly more often than in all the other histological sub‐types combined (8%). Five of the 8 RER+ tumors exhibited most marked type I instability, possibly representing a different mechanism than for the remaining type 2 tumors. The cDNA of the mutation suppression gene hMSH2, the gene most often associated with MI, was screened for alterations in 8 MI‐positive and 5 MI‐negative ovarian tumors. Only 3 changes were found. Complete loss of hMSH2 mRNA expression was detected in 1 tumor, while another expressed only an abnormal transcript containing a deletion of exon 3. One additional RER+ serous adenocarcinoma contained a rare polymophism with a non‐conservative amino acid change. One of 8 RER+ tumors showed loss of heterozygosity at the hMSH2 loci. Genetic instability, caused in part by alterations in the hMSH2 gene, may play an important role in the sporadic endometrioid subtype of ovarian tumors. Other mutator‐phenotype genes may be responsible for the remaining cases of RER+ ovarian tumors. © 1995 Wiley‐Liss, Inc.
Detection of p53 gene alteration in renal‐cell cancer by micropreparation techniques of tumor specimens
Authors: Kuczyk Markus A. , Serth Jürgen , Bokemeyer Carsten , Jonassen Jens , Arndt Heike , Paeslack Ute , Werner Martin , Tan Hong‐Ki , Jonas Udo 
Published: February 2007

AbstractAlterations in the p53 tumor‐suppressor gene have been identified in a variety of human malignancies, including renalcell cancer. A technique for the isolation of tumor areas from tissue specimens to analyze formalin‐fixed and paraffinembedded tumors and try to avoid a disturbance of the results due to genetic background signal by the presence of tumorinfiltrating lymphocytes, was established. The presence of lymphocytes within the tumor areas investigated was determined by immunohistochemical staining for CD3, a lymphatic surface antigen. Following the isolation of about 100‐200 tumor cells, PCR‐directed molecular genetic analysis was performed. A highly informative allelotyping approach for the detection of loss of heterozygosity (LOH), determining BstUI‐ and VNTR‐polymorphisms, a 100‐bp marker directly localized in intron I of the p53 gene, as well as screening for mutations by single‐strand conformation polymorphism analysis (SSCP) in exons 5‐8, were used. Out of 44 renal‐cancer specimens, 33 (75%) were informative for PCR‐directed RFLP‐analysis. Allelic loss at the p53 gene locus was observed in 10 of 33 cases (33%). No correlation between p53 gene alteration and T‐stage, histological grade or histological differentiation could be observed. Alterations in the p53 gene, as detected by a molecular genetic as well as an immunohistochemical approach, were correlated to overall survival. During univariate analysis histological grade, lymphnode status and the presence of distant metastases could be identified as prognostic parameters for overall survival. During multivariate analysis none of the factors investigated remained an independent prognosticator for survival. Summarizing these results, it seems unlikely that p53 gene alterations will serve as an important new factor for the clinical prognosis of patients with renal‐cell cancer. © 1995 Wiley‐Liss, Inc.