Biomedical subjects

E Rambech

Publications and source records attributed to E Rambech.

8 recordsLinked to original sources

PubMed2003

Defective mismatch-repair in patients with multiple primary tumours including colorectal cancer.

Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at least four malignancies, including two colorectal cancers, for studies of the tumour characteristics associated with HNPCC. In total, these individuals developed 209 tumours, 156 of which were successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A concordant loss of expression for the same MMR protein in several tumours from the same individual, a pattern that strongly suggests an underlying germline MMR gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients and MSH2 in 9 patients. We conclude that the development of multiple primary tumours, including synchronous or metachronous colorectal cancers, is associated with an increased frequency of MSI and loss of immunohistochemical expression of MLH1 and MSH2.

Adult↗

PubMed2001

Beta-catenin activation through mutation is rare in rectal cancer.

Increased transcriptional activation through beta-catenin stabilization plays a central role in colorectal tumorigenesis. Alterations of phosphorylation sites within the CTNNB1 gene, which codes for beta-catenin has been reported to occur in about one-half of colorectal tumors without APC-gene mutations. We assessed the importance of mutations in the regulatory domain, located within exon 3 of CTNNB1, in 103 rectal carcinomas and correlated these data with presence of microsatellite instability, somatic frame-shift alterations of the TCF-4 gene, and APC-gene mutations in the tumors. No mutation was detected in exon 3 of the CTNNB1 gene and our results thus demonstrate that beta-catenin activation through mutation rarely contributes to the development of sporadic and microsatellite instability stable rectal cancer.

Adenocarcinoma↗

PubMed2001

Tissue microarray technique in soft tissue sarcoma: immunohistochemical Ki-67 expression in malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) represents a heterogeneous soft tissue sarcoma entity. The authors compared different methods to determine immunohistochemical staining in whole tissue sections, evaluated the tissue microarray technique, and assessed immunohistochemical heterogeneity using the proliferation marker Ki-67 in 47 histopathologic tumor blocks from 11 MFHs. Whole tissue sections were assessed counting 400 cells along a line and counting all cells in 10 high-power fields (0.16 mm2) with mean Ki-67 expression levels of 13% and 11%, respectively. For the tissue microarray technique, two to three 0.6-mm diameter biopsies were studied from each of the 47 tumor blocks. Good correlation was obtained between whole tissue immunohistochemistry and tissue microarray with the microarray method, giving on average 8.6% greater Ki-67 expression levels than the reference method. Immunohistochemical tumor heterogeneity, evaluated using the high-power field method, showed a median standard deviation of 2.3% within the tumor blocks and 2.5% between the blocks from the same tumor. The authors concluded that the tissue microarray technique yields good quality staining and expression levels for Ki-67 comparable with whole tissue methods in MFH, but because of tumor heterogeneity, several tumor blocks ideally should be studied and, because of loss of material in the microarray process, multiple biopsies should be taken. The feasibility of tissue microarray for immunohistochemical studies of soft tissue sarcomas offers new possibilities to study multiple markers in large tumor materials.

Aged↗

PubMed1999

Dominant human herpesvirus type 8 RNA transcripts in classical and AIDS-related Kaposi's sarcoma.

Skin biopsy sections of Kaposi's sarcoma (KS) from 25 patients (5 AIDS-related, 20 classical cases) were histologically staged and hybridized in situ with oligonucleotide probes for constitutively transcribed human herpesvirus 8 (HHV-8) mRNA T0.7 and T1.1 using a colourimetric technique. T1.1 increases during experimental induction of the viral lytic phase in the HHV-8-infected lymphocytes of primary effusion lymphoma and its colourimetric detection in KS cells presumably corresponds to virion production. Immunostaining with anti-CD20, CD45RO, MAC 387, and alpha-smooth muscle actin was performed following T1.1 in situ hybridization (ISH). When the amount of T0.7 was above the detection threshold, the signal was made up of multiple coarse intranuclear dots in most spindle cells. Of the six early-stage lesions, none produced a T1.1 hybridization signal. Two of four AIDS-related and two of eight classical lesions with incipient spindle cell growth produced rare but distinct dense intranuclear T1.1 signals in endothelial cells lining narrow tubes. In contrast, eight of ten (all classical KS) mature spindle cell lesions displayed a signal, scattered in up to 2 per cent of spindled endothelial cells. Cell types other than endothelium produced no T1.1 hybridization signal in double stains. The results are consistent with other published data indicating latent HHV-8 infection in endothelium and its tumour cell progeny, with simultaneous virion production in a small subset of cells. Immunodeficiency may not influence the number of cells lytically infected with HHV-8 in early KS, in contradistinction to other herpesviruses with latent-lytic cycles.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) DNA in Kaposi's sarcoma lesions, AIDS Kaposi's sarcoma cell lines, endothelial Kaposi's sarcoma simulators, and the skin of immunosuppressed patients.

We used the polymerase chain reaction on 63 tissue specimens of histologically staged classic Kaposi's sarcoma (KS) from 40 patients, 14 specimens from 14 acquired immune deficiency syndrome (AIDS)-KS cases (all from the same geographic area over a 10-year period), and peripheral blood mononuclear cells from 1 of the non-AIDS KS patients to amplify a specific 210-bp genomic sequence of the newly discovered KS-associated herpesvirus (KSHV). Also tested were 86 benign and malignant endothelial lesions, which potentially simulated each KS histological stage and were further matched by age approximation and by sex with a classical KS specimen. The lesions included hemangioma, lymphangioma, pyogenic granuloma, and angiosarcoma. KSHV was also sought in multiple well characterized vascular endothelial cell lines from AIDS-KS lesions and in 20 mainly cutaneous benign and malignant lesions from 15 immunosuppressed transplant patients. Overall, 92% of KS tissue specimens, representing 88% of classical KS and 100% of AIDS-KS patients, and in addition the sample of peripheral blood mononuclear cell DNA, were positive as visualized on ethidium bromide gels and confirmed by Southern blot hybridization (only 1 case was negative on gell visualization but positive on Southern blot), thus confirming the close association of KSHV with KS of different clinical forms. None of the various other endothelial lesion, skin lesions in immunosuppressed patients, or AIDS-KS endothelial cell lines contained amplifiable KSHV DNA, which indicates that reactivation of KSHV is not present in the skin lesions of immunosuppressed patients and probably is not a ubiquitous agent that secondarily infects proliferative endothelium. The absence of amplifiable virus DNA in the cultured endothelium of KS suggests that the stimulus for angioproliferation originates in another host cell or under conditions not reproduced in culture. The polymerase chain reaction is a specific and sensitive means of verifying KS in the differential diagnosis of angioproliferative lessons.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Sinonasal T-cell lymphoma in the differential diagnosis of lethal midline granuloma using in situ hybridization for Epstein-Barr virus RNA.

"Lethal midline granuloma" of the upper airways generally encompasses T-cell lymphoma and Wegener's granulomatosis in Western populations. Treatment and outcome for each is different, but their pathological distinction may not always be possible on routine biopsy specimens. Within a defined population between 1947 and 1994, we found 12 cases of primary sinonasal T-cell lymphoma, all with a CD20-, CD3+ immunophenotype in paraffin sections. We studied the occurrence of the Epstein-Barr virus RNA EBER1 using colorimetric in situ hybridization (ISH) with an oligoprobe. All available biopsy specimens from each patient were hybridized to detect the presence of EBER1 in relation to the phase of lymphoma progression. In addition, ISH was performed on 23 cases of nonspecific rhinitis and 10 cases of Wegener's granulomatosis to determine the specificity of the method in the differential diagnosis of inflammatory/ulcerative lesions. In ten cases of lymphoma, initial biopsy specimens showed the early phase with minimal lymphocytic atypia ("polymorphic reticulosis"). Four of these (including one recurrence) had been missed by experienced pathologists, resulting in a diagnostic delay of 2 to 8 yr. The remaining two cases were in the late phase, i.e., malignant grade atypia was apparent in the initial biopsy specimen, and neither was misdiagnosed as being benign. All hybridizable lymphoma sections, regardless of phase of development, gave a strong ISH signal easily detected at low magnification in 50 to 100% of tumor cells. Scattered positive cells were usually present even in necrotic areas. In contrast, no case of Wegener's granulomatosis or nonspecific rhinitis produced a true hybridization signal. We conclude that a negative EBER1 ISH provides strong evidence against T-cell lymphoma in the differential diagnosis of lethal midline granuloma in our population. Conversely, a strong ISH signal for EBER1 in immunohistochemically determined T-cell infiltrates within sinonasal tissues provides strong support for the presence of lymphoma.

Adolescent↗

PubMed1995

Incidence and prognostic significance of t(14;18) translocation in follicle center cell lymphoma of low and high grade. A report from southern Sweden.

BACKGROUND: The t(14;18)(q21;q32) is the most common recurrent genetic defect in follicle center cell lymphoma (FCC). Conflicting reports exist in regard to a possible prognostic significance for the translocation. PATIENTS AND METHODS: In a single center, 102 patients with either low-grade (n = 50) or high-grade (n = 52) FCC (Kiel classification) and a median follow-up of 82 months were retrospectively studied to determine survival in relation to t(14;18) as shown by either PCR of the bcl-2 rearrangement in paraffinized tissue or karyotype analysis. RESULTS: t(14;18) was detected in 30 of 50 (60%) low-grade FCC and in 12 of 52 (23%) high-grade FCC. The presence of the t(14;18) was not related to morphologic bone marrow involvement or other clinical parameters, but it was related to age: in low-grade FCC, patients with t(14;18) were an average of 17 years younger (p = 0.002) than those without the translocation. In the group with high-grade histology, 30% survived beyond 60 months regardless of t(14;18) status (p = 0.92). Patients with low-grade histology and t(14;18) fared better than those without, irrespective of age (p = 0.01). No significant difference in disease-free survival related to t(14;18) was found in either low- or high-grade FCC. CONCLUSIONS: The incidence of t(14;18) is in accord with that of other European reports. T(14;18) does not define a prognostic subset of high-grade FCC, but is significantly correlated with a better survival in low-grade FCC. The association of t(14;18) with younger age and indolent lymphoma is perplexing in light of recent findings of an age-related increase in t(14;18) in normal subjects.

Adult↗

PubMed1995

Determination of nonendemic nasopharyngeal carcinoma by in situ hybridization for Epstein-Barr virus EBER1 RNA: sensitivity and specificity in cervical node metastases.

After time-consuming and costly investigations, patients with neck metastases from an occult primary often receive unnecessarily large radiation volumes to treat a possible origin in the nasopharynx. In this study a colorimetric antisense Epstein-Barr early ribonucleoprotein 1 (EBER1) oligonucleotide probe specific for Epstein-Barr virus RNA was hybridized in situ to metastatic tissue obtained from 18 nasopharyngeal, 54 oral and pharyngeal, and 12 occult carcinomas derived from an unselected population. All 16 nonkeratinizing nasopharyngeal carcinomas (NPCs) were positive for EBER1. Both cases of keratinizing NPC and all 54 other metastases were negative. A single positive case of occult carcinoma indicated its origin from NPC. In retrospect, 7 patients with occult carcinoma had received unnecessary treatment with irradiation to the nasopharynx. Nasopharyngeal carcinoma appears to be a less common origin of occult carcinoma than previously considered. In the proper clinicopathologic context EBER1 in situ hybridization (EBER1-ISH) allows exclusion of NPC with a high degree of accuracy. Thus unnecessarily large radiation volumes and their adverse sequelae may be reduced in the treatment of occult carcinoma. Conversely, a positive result of ISH allows exclusion of further extensive diagnostic procedures.

Adolescent↗