Biomedical subjects

K Hou-Jensen

Publications and source records attributed to K Hou-Jensen.

At least 37 records · Page 2Linked to original sources

PubMed1995

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. No differences in staining pattern or number of positive keratinocytes could be demonstrated between these conditions. The dermatofibromas were negative. The invasive basal cell carcinomas showed abundant p53 positivity. The lack of p53 immunoreactivity in the epidermal basaloid proliferations overlying dermatofibromas indicates that these lesions have not acquired a phenotype as seen in malignant conditions.

Basal Cell Carcinoma↗

PubMed1995

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. Regression was the least reproducible, with level of invasion and type of melanoma in the mid range. Intra-observer variation was uniformly less than inter-observer variation for each variable. For tumour thickness a variance component analysis was done to quantify the variability further. The clinician should not base his choice of treatment entirely on the microscopic classification but take into consideration the clinical course and appearance of the tumour.

Analysis of Variance↗

PubMed1994

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

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Base Sequence↗

PubMed1994

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. A total of 9 different histopathologically characterized primary tumors were analyzed in this study. The TILs in these tumors were found to preferentially express certain TCR V alpha and V beta regions. The differential usage of certain V alpha regions was very pronounced as illustrated by V alpha 4, which was highly expressed in 3/8 tumors, and V alpha 22, which was highly expressed in 4/8 tumors. For comparison, specific highly expressed V alpha regions in control samples of peripheral-blood lymphocytes rarely exceeded 10%. The most highly expressed V beta region was V beta 8, which was highly expressed in 2/8 tumors. For the highly expressed V alpha 4 and V alpha 22 and V beta 8 regions, the high levels may be explained by the in situ clonal or oligoclonal expansion of TIL. In one specific case, the high expression of V beta 8 was due to expansion of a single clone of TILs, as evidenced by a fully readable sequence of the CDR3 (V-D-J) region, determined by direct sequencing of the PCR product corresponding to V beta 8. In contrast, sequence analysis of V alpha 22, which was expressed in the same tumor sample at similar levels, demonstrated the simultaneous presence of 3 different CDR3 (V-J) sequences derived from V alpha 22 transcripts of exactly the same length. The observed preferential use of TCR V alpha and V beta regions suggests the in situ clonal expansion of specific populations of T-cells, possibly reactive with melanoma-associated peptides presented by HLA molecules. The preferential use of TCR V alpha and V beta regions may imply the involvement of a limited number of shared melanoma-associated peptides.

Base Sequence↗

PubMed1994

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. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled "ordinary" tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11b, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigation.

Adolescent↗

PubMed1993

[Significant prognostic factors for recurrence-free survival after surgical treatment of head-neck melanoma].

The clinico-pathological and therapeutic data of 512 patients with clinical stage I invasive head and neck melanoma of the skin were re-evaluated. There were 287 females and 225 males. The median age at primary surgery was 65 years, range 18 to 96 years. The median observation period was 5 years, range 1 month to 25 years. Sex, age, ulcerated tumor and tumor thickness were found by Cox multivariate regression analysis to act as independent prognostic factors for recurrence-free survival. In addition, size of the excision margin was found of no significance for survival without relapse when adjusting for the independent risk factors.

Adolescent↗

PubMed1993

Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

Diagnosis, Differential↗

PubMed1993

P53 protein expression in Hodgkin's disease.

P53 is an oncosuppressor gene which is located on chromosome 17. Mutations of the p53 gene are closely associated with malignant transformation under in vitro conditions and are the most common genetic alteration in human malignancy. Unlike normal p53 protein which is unstable and usually cannot be detected by immunohistology, mutated p53 shows a decreased cell turnover rate and overexpression as compared with the wild-type protein. In this study a panel of four anti-p53 antibodies (PAb240, PAb421, PAb1801 and DO7) was applied to 52 cases of Hodgkin's disease: three cases of nodular lymphocytic predominance (LP), 33 cases of nodular sclerosis (NS), and 16 cases of mixed cellularity (MC). The results show that 53 protein is present in the Hodgkin's- and Reed-Sternberg cells in 82% of NS and 94% of MC, but not in nodular LP. It is suggested that mutations of the p53 gene and loss of normal p53 function are frequent in Hodgkin's disease and may be implicated in the pathogenesis of this disease.

Antibodies, Monoclonal↗

PubMed1993

Melanocytic lesions in a private pathology practice. Comparison of histologic features in different tumor types with particular reference to dysplastic nevi.

This study reviews a total of 1000 melanocytic lesions--two separate 500 consecutive sample groupings from 1980 and 1989, respectively--diagnosed in a private non-hospital-associated pathology practice. Lesions were classified as lentigo simplex, congenital nevus, "common" nevus, dysplastic nevus, blue nevus, Spitz's nevus or malignant melanoma. A comparison of the two periods reveals an increase in dysplastic nevi from one in 1980 to nine in 1989. The histologic changes in these nevi were compared to those of the other tumors. Pronounced cytologic atypia was seen in the melanocytes of a few "common" nevi, but more often in the dysplastic nevi and in all of the melanomas. Slight nuclear atypia was usual in "common" nevi and lentigines, and also fibroplasia, lymphocytic infiltration, vessel proliferation and pigment incontinence were seen in both "common" nevi and dysplastic nevi. It is concluded that no single histologic variable was specific for dysplastic nevi.

Adult↗

PubMed1993

Altered expression of beta-2-microglobulin in basaloid proliferations overlying dermatofibromas.

The epidermis overlying 2-8% of dermatofibromas shows basaloid proliferations that are indistinguishable from superficial basal cell carcinoma. It is well established that basal cell carcinomas uniformly exhibit a strongly reduced expression of HLA class I molecules. Nineteen dermatofibromas with overlying basaloid proliferations were studied by immunohistochemistry using a monoclonal antibody against beta-2-microglobulin, the invariant chain of the HLA class I molecule. The basaloid proliferations exhibited the same strong reduction in expression of beta-2-microglobulin as demonstrated in basal cell carcinomas. We suggest that this phenomenon may represent a proliferative change induced by the mesenchymal cells of the underlying dermatofibroma.

Basal Cell Carcinoma↗

PubMed1993

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. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.

Adult↗

PubMed1992

Skin melanoma of the head and neck. Prognostic factors and recurrence-free survival in 512 patients.

The clinicopathologic and therapeutic data of 512 patients, with clinical Stage I invasive head and neck melanoma of the skin were retrospectively evaluated. There were 287 females and 225 males. Median age at primary surgery was 65 years (range, 18 to 96 years). Median observation period was 5 years (range, 1 month to 25 years). Site of first recurrence was local in 7% (38 of 512), regional in 13% (67 of 512) and distant in 6% (31 of 512). Sex, age, ulcerated tumor, and tumor thickness were found to act as independent risk factors to recurrence-free survival by Cox multivariate regression analysis. In addition, size of excision margin was found to be of no significance to survival without relapse when adjusting for the independent risk factors.

Adult↗

PubMed1991

Treatment of lichen planus with acitretin. A double-blind, placebo-controlled study in 65 patients.

Sixty-five patients with lichen planus were included in a multicenter trial of acitretin. At the end of an 8-week placebo-controlled, double-blind phase, a significantly higher number of patients treated with 30 mg/day acitretin (64%) showed remission or marked improvement compared with placebo (13%). Furthermore, during the subsequent 8-week open phase, 83% of previously placebo-treated patients responded favorably to acitretin therapy. Typical retinoid adverse reactions were present in all patients on active drug. Laboratory studies did not show any clinically significant changes. This study shows that acitretin is an effective and acceptable therapy for severe cases of lichen planus.

Acitretin↗

PubMed1991

The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

Adult↗

PubMed1991

Expression of intercellular adhesion molecule-1 (ICAM-1) in benign naevi and malignant melanomas.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.

Antigens, CD↗

PubMed1991

Changes over the course of time in histological subclassification of Hodgkin's disease in Denmark.

Primary diagnostic lymph node biopsies from 317 patients with Hodgkin's disease pathologic stage (PS) I or II in the prospective randomised trial of the Danish National Hodgkin Study and from 174 patients with Hodgkin's disease stage III or IV examined and treated at the Finsen Institute, Copenhagen, Denmark, were reviewed. The original diagnosis of Hodgkin's disease was made during the period 1971-1983 and was a result of a consensus among three members of a panel of pathologists. In the current study, the histological material was re-examined in order to critically consider and exclude cases which are not histologically diagnostic but microscopically bear resemblance to Hodgkin's disease, to obtain a uniform subclassification in accordance with recent new points of the Rye classification, to examine possible changes in incidence over the course of time and to examine the NS subclassification according to the BNLI proposals. Two cases (0.4%) were reclassified as not being Hodgkin's disease, and 489 cases (99.6%) were reclassified as Hodgkin's disease in the subgroups: LP 7.5% (16.7%), NS 65.1% (54.7%), MC 21.9% (26.4%) and LD 1.2% (1.2%) (the numerals in brackets state the original subgroups). In 9.7% of the cases, the subclass could not be assessed, because the biopsies were too small for subclassification. The difference between the original and the present subclassification could be explained partly by a change in the criteria for the different subgroups and partly by interobserver disagreement. In the histologically reclassified material, the Rye classification lost its prognostic significance. It was not possible to demonstrate a gradual change over the course of time in the relative number of cases in each subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

PubMed1990

Tumor cell concentration and tumor burden in relation to histopathologic subtype and other prognostic factors in early stage Hodgkin's disease. The Danish National Hodgkin Study Group.

Prognostic factors were examined by multivariate analysis after a recent follow-up of the 300 patients with Hodgkin's disease pathologic stage (PS) I or II treated with radiotherapy +/- adjuvant combination chemotherapy in the prospective randomized trial of the Danish National Hodgkin Study. Initial biopsy material was classified according to the Rye histopathologic classification, the grading and subclassification proposed by the British National Lymphoma Investigation (BNLI), and tumor cell concentration in sections. Tumor cell concentration as a prognostic factor turned out to be better than the other classifications. However, if macroscopic tumor burden was taken into account both tumor cell concentration and the other histopathologic classification systems lost their prognostic significance. Significantly, however, a combination of macroscopic tumor burden and tumor cell concentration, yielding an estimate of the total tumor cell burden, was even better than the macroscopic tumor burden as a prognostic factor. In conclusion, a simple tumor cell concentration count seems to be the most useful form of histopathologic subtyping for prognostic purposes in early stage Hodgkin's disease.

Hodgkin Disease↗

PubMed1989

A simplified working formulation of non-Hodgkin's lymphomas based on quantifiable histologic criteria.

Quantifiable criteria for a Simplified Working Formulation of non-Hodgkin's lymphomas are proposed. Biopsy specimens from 582 patients followed from 8.5 to 18.0 years were classified according to the Working Formulation. In addition, on hematoxylin and eosin-stained histologic sections, differential counts among six lymphoma cell types were performed. In each lymphoma 100 cells were counted from representative areas. The intralymphoma variation observed by this method was insignificant for the reproducibility of classification. Five histologic types were defined: (1) follicular small cell (less than or equal to 25% large cells), (2) follicular large cell (greater than 25% large cells), (3) diffuse small (less than or equal to 10% large cells), (4) diffuse large cell (greater than 10% large cells), and (5) lymphoblastic (greater than 20% lymphoblasts). These criteria had clinical significance with regard to prognosis, leukemic conversion, and meningeal involvement. The intraobserver and interobserver reproducibility of the Simplified Working Formulation was, respectively, 91% and 88%.

Cell Count↗