Expression of gp100, MART-1, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group.

With the recent availability of novel antibodies against melanoma antigens tyrosinase and MART-1, it is important to validate their usefulness in pathology practice and in screening patients for immunotherapy treatment. In the present study conducted by the Melanoma Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC-MCG), immunohistochemical staining for gp100 (antibodies NKI-beteb and HMB-45), MART-1 (A103), tyrosinase (T311), and S100 (S100) was compared on formalin-fixed and paraffin-embedded tumour lesions from 80 patients with 130 malignant melanoma lesions, comprising 44 primary tumours, 18 locoregional metastases, 41 lymph node metastases, and 27 visceral metastases from the lung, liver, and brain. A score between 0 and 5 was allocated to each immunohistochemically stained section.

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases.

The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34-91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis.

[Pseudolymphoma and ventricular maltoma in patients with chronic gastritis, ulcer and Helicobacter pylori infection].

Among 128 patients with malignant B-lymphoproliferative disorders, 19 patients had long lasting dyspepsia and gastroscopy showed chronic active gastritis or gastric ulcer. PCR analysis for TCR and IgH clonality in biopsies showed local involvement of the malignant lymphocyte clone in four patients out of eight indicating presence of these cells in the inflammatory infiltrate. Weak B-cell clonality was found in four patients.

Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies.

The PTEN/MMAC1 gene on chromosome 10q23 encodes a lipid phosphatase with tumor-suppressive properties. Germline PTEN/MMAC1 mutations have been implicated as the predisposing factor in Cowden disease and other hamartoma syndromes, and somatic mutations and deletions have been identified in a wide range of human cancers, including 30-40% of metastatic melanoma cell lines. To study further the possible role of PTEN/MMAC1 in the pathogenesis and progression of malignant melanoma, we examined uncultured specimens from 16 primary and 61 metastatic tumors from 67 patients.

Expression of basic fibroblast growth factor and vascular endothelial growth factor in primary and metastatic melanoma from the same patients.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are both recognized as stimulators of migration and angiogenesis during the progression of melanoma. However, the timepoints during tumour progression at which the expression of these angiogenic factors is most essential is still controversial. Using immunohistochemical analyses, melanoma cells were found to express bFGF in 18 out of 19 primary tumours and in 13 out of 20 metastases.

Apoptosis-related genes and proteins in Hodgkin's disease.

During recent years it has become increasingly evident that L&H cells in nodular lymphocytic predominance (LP) Hodgkin's disease (HD) and Hodgkin and Reed-Sternberg (H-RS) cells in approximately half the cases of classical HD originate from B-lymphocytes, and that H-RS cells in most of the remaining cases of classical HD express a null phenotype. The pathogenesis of HD is unknown. An association with Epstein-Barr virus (EBV) has been suggested and there are also indications that genes involved in programmed cell death (apoptosis) may be implicated.

Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.

Objective: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations.

Subjects And Design: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma.

Setting: A university hospital and The State Serum Institute in Copenhagen.

Somatic Fas mutations in non-Hodgkin's lymphoma: association with extranodal disease and autoimmunity.

Fas (APO-1/CD95) is a cell-surface receptor involved in cell death signaling. Germline mutations in the Fas gene have been associated with autoimmune lymphoproliferative syndrome, and somatic Fas mutations have been found in multiple myeloma. We have examined the entire coding region and all splice sites of the Fas gene in 150 cases of non-Hodgkin's lymphoma.

BAX protein is not expressed by basal cell carcinomas.

BAX and related proteins encoded by the BCL2 gene family are involved in the regulation of apoptosis. BAX is an apoptosis-promoting protein. The slow growth of basal cell carcinoma (BCC) has so far been explained by a high apoptotic activity.

Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb.

Mantle cell lymphomas (MCL) are morphologically and immunophenotypically distinctive lymphoid neoplasms characterised by overexpression of cyclin D1. Recent studies have suggested that co-operating aberrations of cell cycle associated genes may provide a growth advantage to a tumour. To address this issue further, we investigated five typical and three aggressive (blastoid) MCL for alterations in the cell cycle regulating genes p15, p16, CDK4, Rb and p53.

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.

Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q.

Analysis of T cell receptor AV and BV chain gene expression by infiltrating lymphocytes in Spitz naevi and in halo naevi.

Spitz naevi and halo naevi are benign melanocytic lesions that share many histological features with malignant melanoma. All lesions are characterized by a brisk infiltration of lymphocytes, mainly of the T cell subtype, and halo naevi are known to undergo spontaneous regression. Since the benign nature of Spitz naevi and halo naevi might therefore be caused by specific T cell responses against tumour-associated antigens, it was found of interest to characterize this T cell response in detail.

Bcl-2 overexpression in basaloid proliferations overlying dermatofibromas and basal cell carcinomas.

Basaloid proliferations overlying dermatofibromas resembling superficial basal cell carcinomas have been interpreted both as reactive/regressive and frankly malignant. Basal cell carcinoma is a slow-growing tumour, which so far has been regarded as an actively proliferating lesion with a high apoptotic activity. We examined immunohistochemically 6,dermatofibromas with overlying simple hyperplasia, 12 dermatofibromas with overlying basaloid proliferations, and 24 basal cell carcinomas for expression of Ki-67 protein, and bcl-2 protein.

Metallothionein expression in basaloid proliferations overlying dermatofibromas and in basal cell carcinomas.

Basaloid proliferations overlying dermatofibromas which morphologically resemble superficial basal cell carcinomas have been interpreted as both reactive/regressive and frankly malignant. Metallothioneins (MTs) are low-molecular-weight proteins with a selective binding affinity for heavy metal ions. MTs has been proposed to represent a biological marker of carcinogenesis and, in a variety of human tumours, a correlation between immunohistochemically overexpression of MT and aggressive clinical behaviour has been shown.

The bone-marrow infiltration pattern in B-cell chronic lymphocytic leukemia is not an important prognostic factor. Danish CLL Study Group.

In a multicentre study of 635 consecutive newly diagnosed patients with B-CLL, the histological bone marrow (BM) specimens were reviewed independently by each of 3 pathologists and found evaluable for BM infiltration pattern in 575 patients, 404 of whom had a CD5+, mainly FMC7-, faint surface-membrane immunoglobulin (SIg) fluorescence-intensity ppenotype. In these 404 patients the following BM infiltration patterns were found: mixed nodular-interstitial (30%), moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In univariate survival analysis, significant differences were found according to BM pattern (p < 0.

p53 protein expression in cutaneous T-cell lymphomas.

p53 is an oncosuppressor gene located on chromosome 17p. Point mutations of the p53 gene are seen frequently in human malignancies, and are closely associated with malignant transformation under in vitro conditions. Mutated p53 protein shows a slow cell turnover rate, and accumulates in cells at the nuclear and/or cytoplasmic level.

Observer variation in histological classification of cutaneous malignant melanoma.

To evaluate the variations within and between observers in the interpretation of important histological prognostic factors, a series of 96 melanoma patients was randomly selected from a database of 1691 patients with cutaneous malignant melanoma. The stained sections were examined on two occasions by four experienced pathologists. Analysis by observed agreement and kappa statistics showed maximal tumour thickness to be the best reproducible variable, with ulceration the second best.

Immunohistochemical detection of p53 in epidermal proliferations overlying dermatofibromas.

Basaloid proliferations of epidermis overlying dermatofibromas and morphologically resembling superficial basal cell carcinomas might possess a malignant potential. In order to elucidate whether these basaloid proliferations share phenotypic characteristics with malignancy, we examined immunohistochemically 19 cases of dermatofibroma with overlying epidermal basaloid proliferations, 10 dermatofibromas with overlying simple epidermal proliferations, and 10 invasive basal cell carcinomas for expression of p53. Simple and basaloid proliferations showed sparse positive immunostaining for p53, as seen in normal epidermis.

Histiocytic sarcomas and monoblastic leukemias. A clinical, histologic, and immunophenotypical study.

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures.

Preferential usage of T-cell receptor alpha beta variable regions among tumor-infiltrating lymphocytes in primary human malignant melanomas.

The usage of T-cell-receptor (TCR) alpha beta variable (V) regions among tumor infiltrating lymphocytes (TILs) in primary human malignant melanomas was characterized using a method based on the polymerase chain reaction (PCR). A panel of 57 different variable-region primers specific for the TCR V alpha I-29 and V beta I-28 was designed, and a semi-quantitative PCR method applicable to formalin-fixed, paraffin-embedded tissues was developed. This semi-quantitative method was demonstrated to be reproducible and to be useful for the assessment of V alpha- and V beta-gene-family usage in formalin-fixed, paraffin-embedded tissue samples.

Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series.

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment.