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M F Avril

Publications and source records attributed to M F Avril.

At least 55 records · Page 3Linked to original sources
PubMed1998

HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance.

Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.

Cell Membrane↗
PubMed1998

Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group.

Germline mutations in the p16 and CDK4 genes have been reported in a subset of melanoma pedigrees, but their prevalence is not well known. We searched for such germline mutations in 48 French melanoma-prone families selected according to two major criteria: families with at least three affected members (n = 20) or families with two affected members, one of them affected before the age of 50 (n = 28), and one additional minor criterion. Sixteen different p16 germline mutations were found in 21 families, while one germline mutation, Arg24His, was detected in the CDK4 gene. The frequency of p16 gene mutation in our sample (44%) is among the highest rates yet reported and the CDK4 mutation is the second mutation detected in this gene worldwide. In summary, our results show frequent involvement of the p16 gene in familial melanoma and confirm the role of the CDK4 gene as a melanoma-predisposing gene.

Adult↗
PubMed1998

Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases.

Several clinical and histopathologic features of 65 CD30+ cutaneous lymphoproliferations were evaluated for their diagnostic value between CD30+ primary versus secondary cutaneous lymphomas and for their prognostic significance. Primary cutaneous disease, spontaneous regression, and absence of extracutaneous spreading (but not age < or =60 years) were associated with a better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were expressed in all types of cutaneous lymphoproliferations. However, epithelial membrane antigen immunoreactivity was more frequently expressed in CD30+ secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression was not associated with spontaneous regression, extracutaneous spreading, or survival. Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1 of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.

Biomarkers, Tumor↗
PubMed1998

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients.

PURPOSE: In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS: Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Cox's regression, respectively. RESULTS: Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION: Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

Adult↗
PubMed1998

Subcutaneous interleukin-2 and interferon-alpha therapy associated with cisplatin monochemotherapy in the treatment of metastatic melanoma.

The anti-tumoral activity of interleukin-2 (IL-2) is well-documented. Although the response rate with this cytokine is low, it appears to be improved when associated with interferon-alpha (INF-alpha) and/or cytotoxic drugs. Aim of this work was to study the efficacy and tolerance of an ambulatory treatment using subcutaneous, low-dose IL-2 with subcutaneous INF-alpha and chemotherapy. We report a multicenter study of ambulatory treatment combining subcutaneous (SC) low-dose IL-2 (9 x 10(6) IU) with SC INF-alpha-2a (3 x 10(6) IU) and cisplatin (100 mg/m2) in 33 patients (13 women and 20 men, 22 to 66 years of age) with metastatic malignant melanoma. Metastases were mainly nodal (54.5%) and pulmonary (51.5%). For 81.8% of patients, this therapy constituted the firstline treatment. The overall response rate at the end of the first maintenance course was 30.3% (3 complete responses and 7 partial responses). Adverse effects were observed in 28 patients (84.8%), but were most often minor (grade 1 or 2 on the WHO toxicity scale). The results confirmed the good tolerance to SC IL-2 and its suitability for ambulatory therapy, as well as the potential benefit of associating IL-2 with cisplatin in the treatment of metastatic melanoma (a possibility considered in two previous studies).

Adult↗
PubMed1997

Diversity of the cytotoxic melanoma-specific immune response: some CTL clones recognize autologous fresh tumor cells and not tumor cell lines.

In the present work, to analyze the heterogeneity of the tumor-specific cytotoxic immune response, a large number of T cell clones were generated from the infiltrate of a tumor-proximal invaded lymph node, and two kinds of melanoma-specific CD8+ CTL clones were derived. The majority of T cell clones (about a hundred) are characterized by a specific lysis of the autologous tumor cell lines. Among 34 of the latter clones, HLA-A2 molecule and MART-1(27-35) peptide have been shown to play a predominant role in tumor recognition. However, no significant amplification at the tumor site was observed for 3 of these CTL. The other kind of tumor-specific CTL (1 oligoclonal and 2 clonal cell lines) did not lyse the autologous melanoma cell lines but lysed the "fresh" autologous tumor cells in a MHC class I-dependent manner. Functional analysis of the two different CTL clones have shown that they did not lyse NK targets, autologous peripheral monocytes, activated T cells, and transformed B cells or any of the few allogeneic cultured and uncultured melanoma cells we tested. TCR repertoire analysis has shown that one of these CTL clones was significantly detectable "in situ" among tumor-infiltrating lymphocytes, while not detectable among PBMC. Such melanoma-specific lymphocytes, which could not have been picked out through conventional screening procedures using tumor cell lines, could potentially play a role in tumor rejection. These results suggest that the immune response analyzed toward melanoma cell lines does not totally reflect the in situ immune status.

Aged↗
PubMed1997

Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

Adult↗
PubMed1997

Intratumoral oxygen tension in metastatic melanoma.

Tumour hypoxia can lead to a decrease in the biological effectiveness of radiation and alkylating agents. Few data are available on oxygen tension (PO2) in melanoma. In 20 patients with past history of melanoma, PO2 was evaluated in normal tissues and suspected metastatic lesions (nodes and skin metastases). Oxygen tension was measured using a needle probe technique (KIMOC-6650 histograph, Eppendorf, Germany), the day before the surgical removal of the suspected metastatic lesion. Histological confirmation of the malignant origin of the removed lesion was obtained in 18 cases. In two cases invasion by the known melanoma was not seen histologically. The median PO2 for normal tissues was 40.5 mmHg. For tumours, the median PO2 was 11.6 mmHg, and it was 17.1 mmHg in nodes and 6.7 mmHg in skin metastases. Very low values (< 2 mmHg) accounted for 20% of the recorded values in nodes and 15% in skin metastases. When analysed according to the node size (< or > or = 3 cm in diameter), the median PO2 was 10.4 mmHg in large nodes (six patients) and 53.3 mmHg in small nodes (six patients). For the two non-tumoral lesions, the median PO2 values were 20.9 and 25.1 mmHg, with no values below 10 mmHg. Thus a decrease in PO2 values, probably corresponding to tumour hypoxia, was found in most of the metastatic tumours when compared with normal tissues. The prognostic value of these PO2 measurements in melanoma remains to be demonstrated in the tumour response to radiotherapy or alkylating agents. However, tumour hypoxia can already be investigated as a target for new treatment modalities in metastatic melanoma.

Adult↗
PubMed1997

Malignant melanoma and granulomatosis.

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Adult↗
PubMed1996

Melanoma in childhood: an EORTC-MCG multicenter study on the clinico-pathological aspects.

Melanoma in children is rare. Nevertheless, it is imperative that clinicians be aware that melanoma does occur in childhood. Yet there is very little information available on the clinico-pathologic variations, and the prognostic parameters of melanoma in children. This report presents the results of a multicenter study of 102 lesions originally diagnosed as cutaneous melanoma, conducted among 5 Western European countries and collected during the period 1961-1994. Criteria for inclusion in the study included: (1) diagnosis of cutaneous melanoma; (2) age up to 16 years at diagnosis; and (3) availability of representative microscopic slides. On the basis of the histologic review only, 60 lesions were confirmed as melanoma, and 42 lesions initially diagnosed as melanoma were reclassified as nevi; 31 of the latter contained a predominance of spindle cells. The only significant parameter associated with the development of metatases or fatal outcome was thickness of more than 2.00 mm. The 5-year survival rate observed in this study was 84%. Based on these findings we conclude that considerable over-diagnosis of melanomas in children occurs. In order, therefore, to give consistent epidemiological data on melanomas in children and to improve proper recognition of their diagnostic features, both by clinicians and by pathologists, we propose to set up a central registry of melanomas in children in Europe, under the auspices of the European Organization for Research and Treatment of Cancer.

Adolescent↗
PubMed1996

Complete remission seven years after treatment for metastatic malignant melanoma.

BACKGROUND: In this study, the authors identified seven-year survivors after completion of the French multicenter Phase II trial of fotemustine for the treatment of metastatic malignant melanoma. METHODS: One hundred sixty-nine patients with metastatic malignant melanoma were included in this Phase II study. One hundred fifty-three patient records were evaluable with an overall response rate of 24.2%. RESULTS: Five of these patients are alive and in complete remission. One patient had a complete response after fotemustine administration and then relapsed. One patient had a partial response. Three patients had stable disease. These five patients underwent surgery for relapse or residual disease and subsequently achieved durable complete remission. CONCLUSIONS: Long term survival may be the outcome after surgical resection of residual metastatic melanoma after chemotherapy.

Antineoplastic Agents↗
PubMed1996

Genetic and epidemiological risk factors for a malignant melanoma-predisposing phenotype: the great number of nevi.

Multiple genetic and epidemiological factors are involved in the etiology of cutaneous malignant melanoma. The phenotype defined by a great number of nevi (GNN) is consistently reported as being a major risk factor for melanoma and is likely to be under genetic control. As part of a large genetic and epidemiologic survey of melanoma in France, our goal was to understand the pattern of inheritance of GNN in 295 nuclear families ascertained through 295 melanoma probands. The GNN phenotype was defined as having 50 or more nevi vs. less than 50 nevi. Four percent of the 295 families included at least 2 GNN cases. We found that sun exposure during holidays and propensity to sunburns were significantly associated with GNN, independent of the occurrence of melanoma. Four segregation analyses of GNN were conducted, using the class D regressive logistic model, which differed according to the sampling procedure chosen (with and without the melanoma probands) and the inclusion or not of the significant risk factors. Three of these analyses led to the detection of a recessive-like major factor, which did not fit a Mendelian pattern of inheritance in two of them. Our results are discussed with respect to the low familial clustering of GNN, the type of analysis conducted, the characteristics of the model used, and the complexity of the mechanisms underlying the GNN phenotype.

Female↗
PubMed1996

Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities.

OBJECTIVE: To test the hypothesis that drug-induced pseudolymphoma and hypersensitivity syndrome are 2 distinct clinical entities. DESIGN: Retrospective study from 1980 to 1993. SETTING: Departments of dermatology and medicine of 5 referral universitary hospitals. PATIENTS: Twenty-four patients who met arbitrary criteria selected as being suggestive of lymphoma, with probable drug cause. Patients with other definite cutaneous drug-induced eruptions were excluded. INTERVENTION: None. MAIN OUTCOME MEASURES: Suspect drugs; clinical, biological, and pathological findings; and evolution of each case and of 110 published case reports. RESULTS: Two groups were separated according to their mode of onset and clinical aspect. Three patients (and 15 cases in the literature) had subacute papulonodular or infiltrated plaques, without visceral involvement. Skin biopsy specimens showed a dense lymphocytic infiltrate mimicking lymphoma. Healing was constant when the drug was stopped. The 21 remaining patients (and 95 published cases) had an acute widespread eruption, with fever, enlarged lymph nodes, and multivisceral involvement. Lymphocytosis, atypical lymphocytes, eosinophilia, hepatitis, and high levels of lactate dehydrogenase were frequent. Skin biopsy findings were usually not specific (lymphocytic infiltrate and keratinocyte necrosis) but sometimes mimicked lymphoma. Severe forms and relapses occurred, even after the drug was stopped. The inducing drugs were the same in the 2 groups. CONCLUSIONS: These 2 groups correspond to drug-induced pseudolymphoma and hypersensitivity syndrome. We think that they are 2 distinct entities with different clinical and biological features and outcome, even if the pathological findings are sometimes similar. Prospective studies are needed to confirm these facts, to evaluate the therapy, and to follow up patients.

Adolescent↗
PubMed1996

[Primary ano-rectal melanoma. Report of 9 cases].

We report nine cases of anorectal melanoma illustrating the histopathological features of these tumors. In all cases, the diagnosis was made at symptomatic stage. Eight patients were treated by surgical procedure which consisted of abdominal perineal resection or local excision. The tumor was either monomorphous, composed of epithelioid or spindle cells, or polymorphous containing both cell types. One case was characterized by small cells resembling plasma cells. Pigmentation was inconstant. Tumor cells were marked by antibodies directed against the S100 protein (9 cases/9), HMB45 (4 cases/7) and vimentin (5 cases/7). As suggested by these cases, the diagnosis of melanoma should be systematically kept in mind in case of an anorectal tumor with unusual histopathological features.

Aged↗
PubMed1995

Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.

Adolescent↗