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Biomedical subjects

L Suter

Publications and source records attributed to L Suter.

At least 19 recordsLinked to original sources
PubMed1995

Expression of MAGE genes in primary and metastatic cutaneous melanoma.

Human genes MAGE-1 and MAGE-3 code for antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. These antigens may constitute useful targets for specific anti-tumor immunization of cancer patients, since genes MAGE-1 and MAGE-3 are expressed in a number of tumors of different histological types, but are not expressed in normal adult tissues other than testis. This also applies to genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3. We have analyzed the expression of these 4 MAGE genes in cutaneous melanoma. Sixteen of 100 primary tumors vs. 69 (48%) of 145 metastases from individual patients expressed MAGE-1. Similar differences in the frequency of gene expression between primary and metastatic tumor samples were observed for MAGE-2, MAGE-3, and MAGE-4. MAGE expression in primary tumors was correlated with tumor thickness: there was a significantly increased frequency in the expression of MAGE-1, -2 and -3 in tumors of greater thickness. Benign and dysplastic nevi, as well as in situ melanomas, did not express any of the 4 MAGE genes.

Adult↗
PubMed1995

Association with clinical outcome of expression of VLA-4 in primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels.

BACKGROUND: The process of tumor growth and metastasis is a complex multistep cascade. The ability of tumor cells to adhere to and detach from extracellular matrix and endothelial cells may be crucial in the metastatic process and may dramatically alter the clinical prognosis and outcome for patients with certain cancers. A number of adhesion molecules have been detected on human melanoma cells and have been associated with various properties in vitro including invasiveness. Recent findings from our laboratory have indicated an ordered change in integrin expression during the process of tumor progression. PURPOSE: This study was designed to identify molecular markers present on human melanoma cells and in intratumoral vessels that have prognostic significance regarding disease-free interval and survival time. METHODS: Specimens of primary cutaneous malignant melanoma were obtained from 60 patients who had been followed for at least 36 months, with development of metastases in 29 patients during that period of time, and were analyzed for their expression of VLA-4, VLA-6, ICAM-1, ELAM-1 (E-selectin), CD62 (P-selectin), and CD44v6 molecules on tumor and endothelial cells by immunostaining. Light microscopy was used to evaluate and categorize the number of positively stained cells. Statistical analyses were done to determine the relationship of the expression of individual adhesion molecules with time to disease progression (i.e., disease-free interval) and overall survival time. RESULTS: In each case, positive staining for ELAM-1 and CD62 on intratumoral vessels and for VLA-4 on human melanoma cells was negatively associated with disease-free interval (P < .01) and overall survival time (P < .01). The presence of VLA-6, CD44v6, and ICAM-1 on melanoma cells was not associated with clinical outcome. CONCLUSIONS: Immunohistochemical screening and detection of ELAM-1, CD62, and VLA-4 may help to define a subgroup of melanoma patients at risk of developing metastases.

Adult↗
PubMed1995

Mast cells in melanocytic tumours.

The importance of mast cells in local homeostasis, inflammation and tumour surveillance is supported by many studies, and the association of mast cells with various neoplasms has been known for a long time. The functional significance of mast cells surrounding tumours is currently unclear. In the present histopathological study, 16 naevi and 44 primary malignant melanomas were analysed. The follow-up time after primary surgery of malignant melanoma patients was almost 10 years, during which time half of the tumours had metastasized. The numbers of mast cells surrounding pigmented lesions were determined. The mast cells were visualized using a modified toluidine blue staining (pH 0.5; 24 h). Significantly different numbers of mast cells were found in naevi compared to melanomas (P = 0.0013), but no significant correlation could be identified regarding prognostic parameters including tumour thickness and clinical outcome.

Adult↗
PubMed1995

[Unusual radiation reaction after soft roentgen radiotherapy in a patient with pemphigus vulgaris].

A 71-year-old woman suffered from pronounced erosion of her nose after soft X-ray therapy (total dose 28 Gy, half dose depth 10.5-11.5 mm). 5 weeks after the end of the irradiation no healing tendency was observed. This unusual clinical course was caused by a simultaneously existing pemphigus vulgaris that worsened after radiotherapy, presumably as a consequence of the release of epidermal antigens. In this case it is improbable that the pemphigus was induced by the radiotherapy, as has been reported on several occasions in the literature. However, this possibility cannot be entirely excluded.

Aged↗
PubMed1991

p-glycoprotein expression in malignant melanoma.

In some human malignancies resistance to chemotherapy is caused by an energy-dependent efflux system, responsible for the removal of chemotherapeutics out of the resistant tumor cells. A major component of this efflux system is the permeability glycoprotein (p-glycoprotein), which depends on the multidrug-resistance gene MDR1. We have tested p-glycoprotein in primary and metastatic human melanoma by use of the monoclonal antibody C219; a substantial expression was only observed in 1/37 primary melanomas and in 1/27 melanoma metastases. None of the patients with negative metastases responded to chemotherapy. Moreover a complete remission of metastatic growth was observed in the patient with the metastasis significantly expressing the p-glycoprotein. Sequential studies revealed no significant increase of p-glycoprotein-positive cells during and after chemotherapy. We conclude that drug resistance in human melanoma does not usually depend on the p-glycoprotein-related efflux system. Other mechanisms are obviously responsible for drug resistance in this human malignancy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

The relationship between characteristics of the tumor cells and sex of the patients in primary malignant melanomas.

Sex is a well proven prognosticator in primary malignant melanoma. We studied 19 parameters of tumor cells in primary malignant melanoma from 391 patients, the purpose being to determine if melanomas in men and women are alike. Apart from results in thin melanomas, no difference was seen between the sex groups. Thin melanomas showed a significant difference for the melanoma-associated antigen G7-E2 (higher expression in women) and the histocompatibility antigen HLA-DR (higher expression in men). The results suggest that sex-related prognostic differences are due more to host than to tumor characteristics.

Antigens, Neoplasm↗
PubMed1991

Radiotherapy of primary human melanomas--experiences and suggestions.

We treated 60 invasive primary human melanomas by soft X-rays. In 23 additional cases radiotherapy was applied after total excision of a primary melanoma. Only in two cases was a tumor observed in the field of irradiation during the follow-up period: a recurrence of a primary melanoma and a skin metastasis. Radioresistance cannot be unequivocally assumed in either case. Since deeply situated in-transit metastases cannot be destroyed by soft X-rays in spite of our good results we regard radiotherapy of invasive primary melanomas as a second choice treatment to be administered if impaired general health, excessive tumor growth in certain localisations or refusal of the patient do not allow a major operation. Nodular parts of primary melanomas should be excised before radiotherapy to obtain material for histopathological confirmation of the diagnosis and to determine the thickness of the tumor. X-rays of lower hardness can subsequently be applied.

Adolescent↗
PubMed1989

Metastatic human melanoma. Phenotypic heterogeneity and antigen expression in relation to the clinical status.

According to animal experiments, metastasis to a particular organ depends on the phenotype of the tumor cells. Widespread metastatic dissemination including internal organs would therefore, at least in part, depend on the capacity of tumor cells to modulate, resulting in increased phenotypic heterogeneity. We found evidence for this assumption in human melanoma by phenotyping metastases (mainly cutaneous/subcutaneous) from 59 patients by the use of six monoclonal antibodies. Interlesional antigenic heterogeneity was present in 22/33 (67%) patients with disseminated metastases including at least one internal organ, but only in 4/26 (15%) patients whose metastases were restricted to skin and/or skin-draining lymph nodes (P less than or equal to 0.01). Chemotherapy cannot be the main reason for interlesional phenotypic heterogeneity, as seen by comparison of treated and untreated patients. Aneuploid melanoma metastases, as an indication for instability on the chromosomal level, were found in the majority of patients (84%) regardless of their clinical situation. Widespread disease was significantly related to the loss of the cytoplasmatic antigen K-1-2 and to the expression of the 130-kDa membrane antigen A-1-43.

Antigens, Neoplasm↗
PubMed1989

The Ki-67 antigen in primary human melanomas--its relationship to mitotic rate and tumor thickness and its stability.

We investigated whether two parameters of proliferative activity - mitotic rate and Ki-67 positive cells - are interchangeable. The mitotic rate was assessed on paraffin-embedded sections, Ki-67 positive cells were immunohistologically determined in frozen tissue. A poor correlation (correlation coefficient r = 0.57) was found between both parameters. The proliferative activity was often not homogeneously distributed in the tested tumors. However, this is a major reason for the observed difference only in thin melanomas (less than 1.5 mm) as seen by comparison of tumors with homogeneous and inhomogeneous proliferative activity. We assume that arrest of cells in different stages of the cell cycle - variable from melanoma to melanoma - is the major reason for the observed discrepancy between mitotic rate and Ki-67 positive cells in tumors of 1.5 mm and thicker. The mean number of Ki-67 positive cells increased with tumor thickness. The stability of the Ki-67 antigen towards freezing, thawing, and formalin was studied.

Antigens, Surface↗
PubMed1988

Architectural features in melanocytic lesions with cellular atypia.

According to the quantity of single atypical melanocytes at the dermoepidermal junction 334 nevi were assigned to 3 groups: (1) with pronounced nuclear and cellular atypia (n = 73); (2) with moderate atypia (n = 127), and (3) without atypical melanocytes (n = 134). Three architectural features were almost exclusively observed in groups 1 and 2 with cellular and nuclear atypia: atypical localization of melanocytes in the epidermis, irregular distribution of melanocytes in the junctional zone and atypical nests of melanocytes. A combination of 2 or 3 of these features was seen in 76% of the nevi with pronounced cellular and nuclear atypia, in 28% of those with moderate atypia and in none of those without atypical melanocytes. Regarding 4 other criteria only minor but still statistically significant differences were found between the 3 groups of nevi. We conclude that these 4 other criteria, i.e. inflammatory infiltrate, lamellar and/or concentric fibroplasia, persisting lentiginous hyperplasia and dust-like pigment in melanocytes and nevus cells are not helpful for the diagnosis of a dysplastic nevus because of their low specificity. Minimal requirements for the diagnosis of a dysplastic nevus are suggested.

Adolescent↗
PubMed1987

Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype.

In order to gain insight into the role of macrophages in human melanoma, we studied fresh-frozen material from 15 dysplastic nevi, 199 primary melanomas, 107 melanoma metastases, and paraffin sections from 98 primary melanomas with the monoclonal antibody 25F9 which recognizes an 86 x 10(3) dalton protein present on a subset of mature human macrophages. Considerable infiltration of tumors with 25F9-positive macrophages was observed in 2 dysplastic nevi (13%), 87 primary melanomas (44%), and 45 metastases (42%). The degree of intratumoral macrophage infiltration correlated with expression of class II HLA-DR antigens on tumor cells, in primary melanoma with a tumor thickness above 0.75 mm, and with the occurrence of metastases within 2 years. In paraffin sections, intratumoral 25F9-positive macrophages also correlated with metastatic spread of primary tumors after longer follow-up. Metastases revealed a higher degree of macrophage infiltration following systemic or local immunotherapy, compared with untreated metastases, or metastases removed during chemotherapy. Of 38 patients who died within an observation period of 1 year, 19 (50%) had considerable infiltration of metastases with 25F9-positive macrophages, whereas this was found in only 4 of 12 patients (33%), who survived for longer than 2 years following metastases removal. A higher degree of 25F9-positive macrophages correlated with a shift towards the T8-positive subsets within the T cell compartment of the infiltrate. Our results suggest that accumulation of 25F9-positive macrophages in melanomas indicates more aggressive tumor properties.

Antibodies, Monoclonal↗
PubMed1986

BCG immunotherapy in stage I melanoma patients. Does it influence prognosis determined by HLA-DR expression in high-risk primary tumors?

Previously, we have provided evidence for a positive correlation between HLA-DR expression in primary melanoma and early metastasis. In the present study we investigated whether this relationship was modified by adjuvant BCG immunotherapy. The study comprised 107 patients with a stage I high-risk melanoma; 44 patients had been treated with BCG, whereas the remaining patients had not received any adjuvant therapy. There was no difference in disease-free survival between BCG-treated and untreated patients. Disease-free survival was significantly shorter in patients with high expression of HLA-DR antigens in the primary tumor. Subgrouping BCG-treated and control patients according to HLA-DR phenotype of the melanoma revealed a prolongation of disease-free survival in the subgroup of BCG-treated patients with no or low expression of HLA-DR antigens in the primary melanoma. BCG therapy apparently did not influence prognosis of patients with high expression of HLA-DR antigens in the tumor.

BCG Vaccine↗
PubMed1986

[Radiotherapy of neoplasms of the facial skin].

Radiotherapy--predominantly with soft x-rays--is, besides plastic surgery and cryosurgery, suitable for the treatment of facial malignancies for which operation would be undesirable in consideration of tumour size and the patient's general health, age and internal diseases. Operation should be preferred for smaller tumours that can be operated on with primary wound closure; tumours that grow into the mouth angle or into the cartilaginous folds of the ear; for patients under 50 years of age; for facial malignancies that have already caused a defect; for patients with nevoid basal cell epithelioma syndrome or xeroderma pigmentosum; for melanomas and sarcomas (except lentigo maligna). Optimal results are achieved by exact limitation of the irradiated area (with a safety margin) and a ray hardness that corresponds to the individual tumour thickness. Due to mechanical irritation, unusually high sun exposure, allergies, pyodermas and local treatment with corticosteroids ulceration may develop in the radioderma remaining after radiotherapy. Radiation-induced tumours occurring in radiodermas are extremely rare if irradiation was applied for a facial malignancy according to the rules and after the 50th year of age.

Aged↗
PubMed1985

Phenotypic dynamics of tumor progression in human malignant melanoma.

The phenotypic changes in human melanoma cells during the course of tumor progression were studied with monoclonal antibodies (MAbs) against the melanoma-associated antigens (MAA) M.2.2.4, H.2.8.10, K.1.2, A.1.43, and A.10.33, and HLA-(A,B,C and D). Cryostat sections of 172 primary melanomas of the skin, 157 melanoma metastases and 56 nevi were investigated with an indirect immunoperoxidase method. Phenotypic heterogeneity was observed within lesions at all stages, and also within different tumors of the same patients. Despite this heterogeneity, principles of antigen expression were found. From the reaction pattern of MAbs, the following classifications of antigens were derived: "constitutive" markers of nevomelanocytic cells (M.2.2.4 and H.2.8.10) were found expressed over a wide range of local and systemic tumors. One MAA, K.1.2 (Suter et al., 1985), that declines with progression of melanoma, was classified as an "early" antigen, whereas MAA that appear in primary melanoma in proportion to invasiveness, and which are expressed in metastases of lymph nodes and visceral organs (A.1.43, and A.10.33), were classified as "late" markers of tumor progression. HLA-antigens were classified as "intermediate" markers, HLA-A,B,C, as an "early-intermediate", and HLA-DR as a "late-intermediate" marker. The occurrence of class II HLA, A.1.43-, and A.10.33-positive tumor cells in primary melanoma indicates a high metastatic potential of tumors, independent of tumor thickness. The data show that local and systemic progression of melanoma is associated with qualitative changes in tumor cells which can be recognized by MAbs.

Antibodies, Monoclonal↗
PubMed1985

A tumor-associated antigen expressed in melanoma cells with lower malignant potential.

The antigen K-1-2, detectable by a MAb is found in nevi and melanomas. It is associated with melanoma cells of low invasive and metastatic potential as shown by immunoperoxidase studies with cell lines, biopsies and autopsies: K-1-2 occurs in melanoma cell line SK-Mel 25, but not in cell line A-375. A-375 has a higher malignant potential than SK-Mel 25 because, in contrast to SK-Mel 25, it produces plasminogen activator and grows in nude mice. K-1-2 was frequently strongly expressed (greater than or equal to 50% cells positive) in flat (less than 1.5 mm) and less frequently in medium and thick primary tumors. In thick primary melanomas K-1-2 positive cells were confined to the junctional zone or to marginal, flat areas of the tumor. Only rarely does K-1-2 occur in metastases. Strong expression of the K-1-2 antigen was found less often in primary melanomas, which develop early metastases, than in tumors that had not metastasized during an observation period of 18 months. In 5 patients with disseminated metastatic disease, metastases strongly expressing K-1-2 and those negative for this marker or containing only a minor percentage of K-1-2 positive cells were observed simultaneously or at different times. These findings suggest that a change from high malignancy to low malignancy--as observed in animal systems--may also occur in human melanoma.

Animals↗
PubMed1985

[Multiple primary malignant melanomas].

We report on a 54-year-old woman who developed 6 melanomas and 9 lentigines malignae in 5 years. Five of the 6 melanomas were malignant lentigo melanomas. In one case it was not possible to differentiate between malignant lentigo melanoma and superficial spreading melanoma. Intensive exposure of the corresponding localizations (face, arms and back) to sunlight over many years was the only risk factor known in this case. In spite of multiple tumors, the prognosis is relatively good for this patient, because the risk of recurrence or metastasis does not multiply but depends on the prognostically most unfavorable tumor (0.65 mm--level III--with regression zone).

Female↗
PubMed1984

HLA-DR antigen expression in primary melanomas of the skin.

Ninety-three primary malignant melanomas of the skin were typed immunohistologically for the expression of HLA-DR on tumor cells. HLA-DR-positive stroma cells were HLA-DR-negative or only locally positive in most cases. In 36 (39%) of the lesions more than 10% of the tumor cells were stained by two monoclonal antibodies against the nonpolymorphic portion of HLA-DR. HLA-DR-positive tumor cells were often accumulated at the advancing front of the melanoma. The occurrence of HLA-DR-positive tumor cells was related to tumor thickness and level of invasion. Substantial numbers of HLA-DR-positive tumor cells were found in half of the tumors thicker than 1.5 mm and in only 18% of flatter lesions. The highest percentage of HLA-DR-positive tumors was found in the group of melanomas invading the reticular dermis (level IV). The majority of tumors (18/24) that had metastasized within an observation period of 0-32 months were HLA-DR-positive. Regarding the mononuclear cell infiltrate, no correlation between the degree of overall infiltrate and the expression of HLA-DR by the tumor cells was found. The infiltrate within the tumor, however, was more often marked in HLA-DR-positive than in HLA-DR-negative melanomas.

Antibodies, Monoclonal↗