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C J Meijer

Publications and source records attributed to C J Meijer.

At least 109 records · Page 6Linked to original sources
PubMed1999

Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.

A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.

Antibodies, Viral↗
PubMed1999

Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects.

Sarcomatoid carcinomas and carcinosarcomas are histologically malignant biphasic neoplasms with an epithelial and a spindle cell component. Both a polyclonal and a monoclonal origin have been postulated for these tumours, but the latter has been favoured. For carcinosarcoma, the stem cell from which the epithelial and mesenchymal components are derived is expected to be more immature than the epithelial stem cell from which different components of sarcomatoid carcinoma originate, since in the latter, immunohistochemical or ultrastructural epithelial characteristics are still detectable. In the present study, comparative genomic hybridization was used to test the hypothesis that both tumour components in sarcomatoid carcinoma have more chromosomal aberrations in common than those in carcinosarcoma. From three sarcomatoid carcinomas originating from the urinary bladder and two carcinosarcomas from the pharynx, the epithelial and spindle cell components were microdissected and analysed for their respective chromosomal aberrations, using comparative genomic hybridization. High-level homology was seen in chromosomal aberrations between the different components in each tumour. This level of homology was even higher in the carcinosarcomas (65 and 91 per cent) than in both sarcomatoid carcinomas (21-51 per cent). The different phenotypic components of both sarcomatoid carcinoma and carcinosarcoma show a large overlap of chromosomal aberrations, strongly suggesting a monoclonal origin for all of these tumours. These findings do not support the hypothesis that the divergence between epithelial and spindle cell components occurs at an earlier stage in carcinosarcomas than in sarcomatoid carcinoma.

Carcinoma↗
PubMed1999

Expression of Fas and Fas ligand in cutaneous B-cell lymphomas.

Primary cutaneous B-cell lymphomas (CBCLs) represent a rare, but distinct group of B-cell neoplasms with a different clinical behaviour to B-cell lymphomas secondarily involving the skin. Fas-Fas ligand (Fasl) expression was investigated in a group of primary and secondary CBCLs to gain an insight into the putative role of these apoptotic molecules in the clinical behaviour of these lymphomas. Frozen and paraffin sections from 32 patients with a CBCL were investigated for Fas and Fasl expression, using immunohistochemistry. This group included 24 primary CBCLs [14 primary cutaneous follicle centre cell lymphomas (PCFCCLs), six primary cutaneous large B-cell lymphomas (PCLBCLs) on the leg, and four primary cutaneous immunocytomas] and eight secondary CBCLs. The results were correlated with follow-up data, bcl-2, and ICAM-1 expression. High Fas expression and absent or low Fasl expression were detected in the vast majority of PCFCCLs and immunocytomas. The group of PCLBCLs on the leg, which have an intermediate prognosis, showed variable results with relatively higher Fasl expression. The highest Fasl expression was found in the more aggressive secondary CBCLs whereas in this group, Fas was undetectable in five of eight cases. Statistical analysis showed that Fas and ICAM-1 expression was strongly related to a favourable prognosis, whereas expression of Fasl and bcl-2 was related to a very poor prognosis. Although only type of CBCL and age, but not Fas, Fasl, bcl-2, and ICAM-1 expression, proved independent prognostic parameters using multivariate analysis, the results of this study suggest that differences in the expression of Fas and Fasl, as well as bcl-2 and ICAM-1, contribute to the differences in clinical behaviour between these different types of CBCL.

Adult↗
PubMed1999

Pathological investigation of sentinel lymph nodes.

The sentinel lymph-node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph-node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects as a result of lymph-node dissection. The task of the pathologist is to screen SNs for metastases. To this end, several techniques are available such as standard histo- and cytopathological techniques, immunohistochemistry, flow cytometry, and molecular biological techniques. These methods are explained and their sensitivity for detecting SN metastases is discussed. Some of these techniques also appear to be useful for intra-operative evaluation of SNs. The standard protocol for detection of SN metastases consists of extensive histopathological investigation including step H&E stained sections and immunohistochemistry. Intra-operative frozen-section analysis of SNs has been shown to be reliable for breast-cancer axillary lymph nodes. In the intra-operative setting, imprint cytology can also be used but its additional value to frozen section analysis is not yet clear. Further studies are necessary to establish the role of sophisticated molecular biological techniques such as reverse transcription polymerase chain reaction (RT-PCR) in detecting SN metastases. The sensitivity of flow cytometry is too low for this purpose.

Biopsy↗
PubMed1999

Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior.

Cutaneous T cell lymphomas (CTCL) generally have the phenotype of CD3+, CD4+, CD45RO+ memory T cells. CTCL expressing a CD8+ T cell phenotype are extremely rare and ill-defined. To elucidate whether these CD8+ CTCL represent a distinct disease entity, the clinical, histological, and immunophenotypical features of 17 CD8+ CTCL were reviewed. None of the 17 cases expressed markers characteristic of natural killer cells or gamma/delta T cells. Nine of 17 cases showed the characteristic clinical and histological features as well as clinical behavior of well defined types of CTCL, such as mycosis fungoides (2 cases), pagetoid reticulosis (2 cases), lymphomatoid papulosis (2 cases), and CD30+ large T cell lymphoma (2 cases), all of which usually express a CD4+ T cell phenotype, and 1 case of subcutaneous panniculitis-like T cell lymphoma. The other 8 cases formed a homogeneous group showing a distinctive set of clinicopathological and immunophenotypical features, not consistent with that of other well defined types of CTCL. Clinical characteristics included presentation with generalized patches, plaques, papulonodules, and tumors mimicking disseminated pagetoid reticulosis; metastatic spread to unusual sites, such as the lung, testis, central nervous system, and oral cavity, but not to the lymph nodes; and an aggressive course (median survival, 32 months). Histologically, these lymphomas were characterized by band-like infiltrates consisting of pleomorphic T cells or immunoblasts, showing a diffuse infiltration of an acanthotic epidermis with variable degrees of spongiosis, intraepidermal blistering, and necrosis. The neoplastic cells showed a high Ki-67 proliferation index and expression of CD3, CD8, CD7, CD45RA, betaF1, and TIA-1 markers, whereas CD2 and CD5 were frequently lost. Expression of TIA-1 pointed out that these lymphomas are derived from a cytotoxic T cell subset. The results of this and other studies reviewed herein suggest that these strongly epidermotropic primary cutaneous CD8+ cytotoxic T cell lymphomas represent a distinct type of CTCL with an aggressive clinical behavior.

Adult↗
PubMed1999

Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease.

Granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA-1) are cytotoxic proteins that are specifically expressed by cytotoxic CD4 or CD8 positive T cells and natural killer cells. Recent studies demonstrated frequent expression of GrB and TIA-1 by neoplastic cells in primary cutaneous CD30(+) large T-cell lymphomas and lymphomatoid papulosis but not in CD30(-) large T-cell lymphomas. In the present study, 74 biopsies from 54 patients with mycosis fungoides (MF) were investigated for the expression of GrB and TIA-1 using immunohistochemistry on paraffin sections. Staining of more than 10% of the neoplastic T cells for GrB or TIA-1 was considered positive. All but two follow-up biopsies had been obtained from patients without extracutaneous disease at the time of biopsy. Expression of TIA-1 and GrB was found in 33 (45%) and 14 (19%) of 74 MF biopsies, respectively. Comparison of biopsies from T3NoMo-stage MF (n = 27) and T2NoMo-stage MF (n = 45) showed increased expression of TIA-1 (55 versus 37%) and GrB (33 versus 9%) in T3NoMo-stage MF. Evaluation of multiple sequential biopsies from successive stages of MF also revealed an increase in the GrB/TIA-1 expression with tumor progression in five of eight cases. A clearcut relation between the expression of TIA-1 and/or GrB and the type of skin lesion biopsied was found. Considering all 74 biopsies, expression of TIA-1 and GrB was found in 18 of 50 (35%) and 5 of 50 (10%) patches or plaques, 9 of 16 (55%) and 3 of 16 (20%) tumors without blastic transformation, and 6 of 8 (75%) and 6 of 8 (75%) tumors with blastic transformation (defined as >50% blast cells). Correlation between GrB/TIA-1 expression in first diagnostic biopsies from patches or plaques from 40 patients with T2NoMo-stage MF and clinical follow-up data did not reveal differences in clinical behavior and survival between patients with (n = 14) or without (n = 26) expression of cytotoxic proteins, indicating that MF expressing cytotoxic proteins should not be considered as a separate group.

Antigens, CD↗
PubMed1999

Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction.

OBJECTIVE: Impaired perfusion of the myocardium induces a local inflammatory response. In animal models, there is ample evidence that polymorphonuclear leucocytes (PMNs) infiltrating infarcted myocardium contribute significantly to infarct size. METHODS: To explore a possible role for PMNs in the tissue damage of human myocardial infarction, we investigated localization of intercellular adhesion molecule-1 (ICAM-1) and CD66b (previously clustered as CD67), a marker of degranulation of human PMNs, in relation to deposition of complement in tissue specimens of infarcted and healthy parts of the heart obtained from 20 patients, who had died following acute myocardial infarction. RESULTS: ICAM-1 was transiently expressed by endothelium and for a longer period (few days) on myofibers of infarcted myocardium. This expression only occurred in parts that stained positive for complement. PMN infiltration exclusively occurred in areas with ICAM-1 expression, but not every ICAM-1-positive area contained PMN infiltrates. CD66b was found in PMNs but was also fixed to the plasma membrane of myofibers that stained positive for complement and ICAM-1. CONCLUSION: These findings indicate that, in infarcted human myocardium, PMNs are degranulated, possibly upon interaction with ICAM-1 and activated complement.

Aged↗
PubMed1999

Influence of chemotherapy on the expression of p53, HER-2/neu and proliferation markers in ovarian cancer.

OBJECTIVE: Mutated p53 and HER-2/neu play a role in the etiology of ovarian cancer. It is important to know whether the expression of these proteins is affected by platinum-containing chemotherapy. STUDY DESIGN: Together with the cell proliferation markers Ki-67 and PCNA, the expression of p53 and HER-2/neu was assessed before and after chemotherapy. Paraffin-embedded tumor sections from 20 patients with ovarian cancer and four patients with benign disorders of the ovaries (controls) were analyzed. The expression of p53 was determined by the antibodies DO-1 and BP53-12. In addition to HER-2/neu and PCNA specific antibodies, MIB-1 was used to detect Ki-67. RESULTS: The expression of all markers was higher in ovarian cancer patients than in non-malignant controls. MIB-1 showed a significant increase of expression after chemotherapy (P=0.002). HER-2/neu, p53 and PCNA also showed a clear increase after treatment, but this was not statistically significant. HER-2/neu is of prognostic relevance with respect to the response to chemotherapy (P=0.005) and survival (P=0.0002). CONCLUSION: The different markers tested all increase after chemotherapy, but the differences are not statistically significant. Low HER-2/neu expression correlates with good outcome at second look.

Adult↗
PubMed1999

Differences in cytokine mRNA profiles between premalignant and malignant lesions of the uterine cervix.

The aim of this study was to assess the expression of cytokine transcripts, reflecting the type of ongoing immune responses at the site of human papillomavirus (HPV) infection, in relation to the development of cervical neoplasia. To this end reverse transcription-polymerase chain reaction (RT-PCR) was performed for interferon (IFN) gamma, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12 (p35 and p40), and transforming growth factor (TGF beta 1) in snap-frozen cervical biopsies, which were tested for the presence of high risk HPV DNA and histologically classified from normal to invasive carcinoma (n = 40). IFN gamma, IL-10 and IL-12 (p35 and p40) transcripts were found to be expressed at significantly lower frequencies in invasive carcinoma as compared with premalignant biopsies (P = 0.006, P = 0.007 and P = 0.002, respectively). IFN gamma IL-10 mRNA were associated with the presence of the IL-12 p35 and p40 transcripts (P = 0.008 and P < 0.00001, respectively). These results are consistent with a locally reduced cellular (type 1) immunity correlating with HPV-induced invasive cervical carcinoma.

Adult↗
PubMed1999

Balance of cell proliferation and apoptosis in breast carcinogenesis.

We determined the mitotic and apoptotic index through the spectrum of pre-invasive ductal breast lesions to invasive carcinoma in search of disturbances in the proliferation/cell death balance in breast carcinogenesis. Seventy-two pure pre-invasive ductal breast lesions (without invasive carcinoma) and 103 invasive breast carcinomas were used. The numbers of mitotic and apoptotic cells were microscopically counted in hematoxylin and eosin stained sections (MI and AI, respectively), and the ratio of the values of MI and AI was calculated for each individual case (M/A index). A distinction was made between well differentiated and poorly differentiated breast lesions, based on histological type and nuclear grade, to arrive at two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 6-fold from DCIS to well differentiated invasive carcinoma. The AI remained in the same range, resulting in a 4-fold increase of the M/A index. For the poorly differentiated breast lesions, a significant increase in MI and AI was found from hyperplasia to poorly differentiated DCIS. From DCIS to poorly differentiated invasive carcinoma, the MI increased significantly and the AI decreased 2-fold (n.s.), resulting in a 2.5-fold significant increase of the M/A index. In conclusion, the net increase of the number of cells in the transition from well differentiated pre-invasive to well differentiated invasive carcinoma is accompanied by an increase of cell proliferation rather than decrease in apoptosis, suggesting that in these lesions, proliferation related mechanisms are most important in carcinogenesis and progression. In contrast, in poorly differentiated breast lesions, decreased apoptosis seems to be also important in carcinogenesis and progression. At present, we are gathering patients with invasive breast cancer who had a previous biopsy with a pre-invasive lesion to obtain further more direct evidence for this hypothesis.

Apoptosis↗
PubMed1999

Expression of CD3-zeta on T-cells in primary cervical carcinoma and in metastasis-positive and -negative pelvic lymph nodes.

Lymphocytic infiltrate is often present in cervical cancer lesions, possibly reflecting an ongoing, but ineffective, immune response to the tumour. Recently, evidence has accumulated for systemically impaired T-cell functions in cancer patients, associated with decreased expression of signal-transducing zeta (zeta) chain dimer molecules on circulating T-cells and NK-cells. Here, we report on the intralesional down-regulation of zeta chain expression on T-cells in cervical carcinoma. Paraffin-embedded or snap-frozen sections from 24 different cervical cancer specimens were studied. Paraffin-embedded tumour-positive (n = 7) and tumour-negative (n = 15) pelvic lymph nodes were also included in the study. Immunostaining was performed on consecutive sections with antibodies specific for CD3-epsilon or the CD3-associated zeta chain dimer. Antigen retrieval by sodium citrate/microwave treatment was essential for zeta staining of paraffin sections. The amount of zeta positive cells was quantitated and related to the number of CD3-epsilon+ cells in corresponding tumour areas. Of the 24 cervical cancer specimens studied, zeta chain dimer expression was reduced in seven cases and strongly reduced in the other 17 samples. In tonsil control sections, CD3-epsilon and CD3-zeta were always co-expressed in almost equal numbers. Also, both tumour-negative and -positive lymph nodes showed zeta chain expression which equalled that of CD3-epsilon expression. These data indicate that a decreased expression of signal-transducing zeta molecules on tumour-infiltrating T-cells is frequent in cervical cancer. The apparently unimpaired zeta chain expression within draining lymph nodes suggests that local tumour-derived factors at the primary site are instrumental in zeta chain down-regulation.

Adult↗
PubMed1999

A quantitative polymerase chain reaction-enzyme immunoassay for accurate measurements of human papillomavirus type 16 DNA levels in cervical scrapings.

A quantitative polymerase chain reaction-enzyme immunoassay (Q-PCR-EIA) was developed to measure the amount of human papillomavirus (HPV) 16 DNA per genome equivalent in cervical scrapings. The quantitative approach was based on a combined competitive PCR for both HPV 16, using the general primer GP5+/6+ PCR, and beta-globin DNA. The two competitive PCRs involve co-amplification of target sequences and exogenously added DNA constructs carrying a rearranged 30 bp sequence in the probe-binding region. The accuracy of quantification by combining the two competitive PCR assays was validated on mixtures of HPV 16 containing cervical cancer cells of CaSki and SiHa cell lines. Comparison of this fully quantitative PCR assay with two semi-quantitative HPV PCR assays on a series of crude cell suspensions from HPV 16 containing cervical scrapings revealed remarkable differences in the calculated relative HPV load between samples. We found evidence that correction for both intertube variations in PCR efficiency and number of input cells/integrity of DNA significantly influence the outcome of studies on viral DNA load in crude cell suspensions of cervical scrapings. Therefore, accurate measurements on viral DNA load in cervical scrapings require corrections for these phenomena, which can be achieved by application of this fully quantitative approach.

Base Sequence↗
PubMed1999

Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oral squamous cell carcinomas.

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the secretory pathway of perforin/granzymes to kill their target cells. In contrast to NK cells, CTL responses are MHC class I restricted. In this study we analysed the relative activation of CTL and NK cells in relation with MHC class I expression on oral squamous cell carcinomas (OSCCs). MHC class I expression was investigated in 47 OSCCs by immunohistochemistry using HCA2, HC10 and beta2-m antibodies. The presence of CTLs, NK cells, and its activation, was investigated in 21 of these OSCCs using respectively, CD8, CD57 and GrB7 antibodies. The Q-Prodit measuring system was used for quantification of cytotoxic cells. All OSCCs showed weak or absent staining of beta2-m on the cell surface. The absence of beta2-m was significantly associated with absent expression of MHC class I heavy chain as detected by HC10 antibody (P = 0.004). In tumour infiltrates CTLs always outnumbered NK cells, as reflected by the ratio CD57/CD8 being always inferior to one (mean: 0.19; SD: 0.15). The proportion of activated cytotoxic cells as detected by granzyme B expression was generally low (mean: 8.6%; SD 8.9). A clear correlation between MHC class I expression and the relative proportion of NK cells/CTLs was not found. This study shows that the majority of OSCCs show weak or absent expression of MHC class I molecules on the cell surface, possibly due to alterations in the normal beta2-m pathway. The low proportion of granzyme B-positive CTLs/NK cells indicates that the secretory pathway of cytotoxicity is poor in these patients. The lack of correlation between MHC class I expression and CTL/NK cell activation as detected by granzyme-B expression suggests that, next to poor antigen presentation, also local factors seem to determine the final outcome of the cytotoxic immune response.

Adult↗
PubMed1999

Restricted low-level human antibody responses against Epstein-Barr virus (EBV)-encoded latent membrane protein 1 in a subgroup of patients with EBV-associated diseases.

Human antibody responses to latent membrane protein 1 (LMP1) in patients with Epstein-Barr virus (EBV)-related disease syndromes were analyzed in detail. Only by immunoblot analysis with purified recombinant LMP1 and by IFA on recombinant LMP1-expressing insect cells could human antibodies directed against LMP1 be detected. Low serum levels of LMP1-directed antibodies could be detected in 3 of 8 EBV-positive Hodgkin's disease patients, 3 of 40 nasopharyngeal carcinoma patients, 2 of 23 Burkitt's lymphoma patients, and 1 of 27 non-Burkitt's lymphoma patients. No LMP1-directed antibodies could be detected in healthy EBV carriers, infectious mononucleosis patients, or patients with chronic EBV disease. All sera contained significant levels of EBV antibodies directed against the immunodominant EBV proteins and peptides. From this study, it can be concluded that LMP1 is a protein with a very low immunogenicity for the humoral immune response in humans.

Amino Acid Sequence↗
PubMed1999

EORTC classification for primary cutaneous lymphomas: the best guide to good clinical management. European Organization for Research and Treatment of Cancer.

In 1997 the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC) published a proposal for a classification for the group of primary cutaneous lymphomas (1). The EORTC classification is the first and only classification that is designed exclusively for the group of primary cutaneous lymphomas. It is also the only classification that has been clinically validated for this group of diseases. As illustrated by this special issue, this classification has resulted not only in the discussion of the definition and terminology of some types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL), but also in a discussion of whether organ-based classification schemes (separate from existing hematopathologic classification schemes for non-Hodgkin lymphomas) should be used. This article explains why it was necessary to create a separate classification for the group of primary cutaneous lymphomas. A short introduction on the history of the classification of cutaneous lymphomas is provided. Next, the basic principles of the EORTC classification are presented. Finally, controversies between the EORTC classification versus the REAL classification (2) and the proposed WHO classification (3), which still impede the usage of one common classification system, are discussed.

Humans↗