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Biomedical subjects

P Validire

Publications and source records attributed to P Validire.

At least 55 records · Page 3Linked to original sources

N-MYC amplification, loss of heterozygosity on the short arm of chromosome 1 and DNA ploidy in retinoblastoma.

Recurrent genetic alterations different from the alteration of the RB1 gene on chromosome 13q14 have been described in retinoblastoma, including structural alterations on the short arm of chromosome 1 and amplification of the N-MYC oncogene. These two genetic alterations are major prognostic factors in neuroblastoma, another embryonic neuro-ectodermal tumour. In order to assess the frequency of these alterations and their possible association with clinical parameters in retinoblastoma, we studied a series of 46 retinoblastoma tumour samples. Ploidy was assessed by flow cytometry, N-MYC copy number was evaluated by a spot-blot procedure using the pNb-1 probe and loss of heterozygosity was investigated by PCR analysis at mini- and microsatellites located on the short arm of chromosome 1. Most tumours were in the diploid or near diploid range; only one case exhibited tetraploidy. N-MYC amplification was observed in only one of the 45 tumours. Loss of heterozygosity on the short arm of chromosome 1 was observed in 9/43 tumours (21%); in particular, its incidence was higher in metastatic than in localised disease (P < 0.05). We suggest that alterations of one or several genes on chromosome 1p might play a role in the oncogenesis or progression of retinoblastoma. Analysis of the long term follow-up of these and additional patients should determine the prognostic value of this parameter.

Child, Preschool↗

Frequent association of human papillomavirus 16 and 18 DNA with anal squamous cell and basaloid carcinoma.

Human papillomaviruses (HPVs) play a major role in the development of genital neoplasia. Their role in anal carcinogenesis is less clear, and the rate of HPV genome detected in invasive anal carcinoma varies considerably in the different reports. Moreover, the relationship of HPV to basaloid carcinoma, claimed to represent a histologic type different from the common squamous cell carcinoma, is still controversial. By use of both polymerase chain reaction and Southern blot hybridization on DNA extracted from frozen tissue specimens, we looked for HPV sequences in 12 cases of squamous cell carcinoma, in 9 cases of basaloid invasive carcinoma, in 1 case of carcinoma in situ, and in 1 case of Paget's disease of the anal canal. We have looked for correlations between virologic data and histologic types of tumors, and analyzed the clinical characteristics of HPV-positive and HPV-negative lesions. In our series, 20 (74%) of 27 cases of invasive anal carcinoma were positive for HPV DNA by Southern blot hybridization and/or polymerase chain reaction. HPV 16 DNA was found in 17 cases, HPV 18 in 2 cases, and in 1 case, the type of the HPV sequences detected remained undetermined (HPV X). Histovirologic correlations showed that 12 of 18 squamous cell carcinomas were associated with HPV 16 and that 8 of 9 cases of basaloid carcinoma were HPV positive; 5 case corresponded to HPV 16, 2 cases to HPV 18, and 1 case to HPV X. The carcinoma in situ case and the Paget's disease case were negative. An analysis of these data within the framework of the literature indicates that approximately 75% of cases of invasive anal carcinoma can actually be considered associated with HPV sequences. Basaloid carcinoma is also frequently associated with HPV genomes and is more likely to represent a histologic variant of squamous cell carcinoma than a separate entity. No clinical characteristics related to the HPV status of the tumors were observed in our series. Epidemiologic data on cervical, anal, and vulvar neoplasia are compared and their relation to the oncogenic properties of HPV in these different tissues are discussed.

Adult↗

[Facial myofibroma of the newborn simulating sarcoma].

INTRODUCTION: Myofibromatosis is a rare but probably under estimated tumor. OBSERVATION: We report a case of a newborn presenting with a facial tumor suggestive of sarcoma. Discrepancy between clinical features and histologic pattern of angioma suggested the diagnosis of myofibroma. The diagnostic of myofibromatosis was made later by specific labelling (actin-smooth muscle) and was confirmed by major spontaneous involution. DISCUSSION: The histology of myofibroma associates fibrous and angiomatous patterns that may be confusing when examining a small biopsy. Due to confusing semiology and histology, subcutaneous myofibromas are certainly misdiagnosed and specific actin labelling (actin, HHF 35) may be of interest. Myofibromas are the most frequent tumor among fibromatoses. The diagnosis should be suspected on the stony consistence of the tumor uncompatible with angiomatous histology. Contrary to multicentric myofibromas of which the prognosis depends on visceral involvement and compressions (72 p. 100 of fatal outcome), solitary subcutaneous myofibroma has a very good prognosis with spontaneous involution.

Diagnosis, Differential↗

[Metaplastic breast cancer with chondroid differentiation. Report of three cases].

The authors report three cases of breast carcinoma with chondroid metaplasia. These three tumors were characterized by direct transition between the carcinomatous and the mesenchymal component. Immunohistochemical study revealed epithelial antigens within the mesenchymal appearing component. Pitfalls in the diagnosis and in the classification of metaplastic carcinomas are reviewed.

Adult↗

The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients.

BACKGROUND: Orbital involvement is a rare occurrence in retinoblastoma but still carries a bad prognosis. The aim of this study was to define more clearly the role of chemotherapy in this advanced disease. METHODS: Between 1977 and 1991, 33 patients were treated at the Services de Pédiatrie at Institut Curie (Paris, France) for orbital involvement of retinoblastoma, which was isolated in 20 patients and associated with metastases in 13 patients (outside the central nervous system [CNS], 6; within the CNS, 7). Treatment included chemotherapy for 33 patients, irradiation of the orbit for 23 patients, and intrathecal chemotherapy and/or CNS irradiation in selected patients. RESULTS: The plateau phase of the survival curve was reached at 15 months, with a survival of 34% plus or minus 8%. The disease free interval was longer when patients had no CNS disease (P < 0.05). Twenty of the 21 recurrences (95%) occurred within 1 year after diagnosis of orbital involvement. CONCLUSIONS: Intensive chemotherapy using cyclophosphamide, platinum compounds, epipodophyllotoxins, doxorubicin, and vincristine was effective in orbital involvement of retinoblastoma even with associated extra-CNS metastases. However, associated CNS disease still carries a bad prognosis, and long term follow-up is necessary to evaluate the risk of a second tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Cytogenetic study of 30 colorectal adenomas.

The cytogenetic analysis of 30 colorectal adenomas obtained from 24 patients is reported. Only normal karyotypes were observed in eight cases. Among the 22 adenomas with abnormal karyotypes, 15 showed clonal anomalies. Chromosome gains involving chromosomes 13, 20, 7, 9, and 12 were recurrently observed. Chromosome 18 was frequently lost or involved in translocations at bands q21-q22. More chromosome alterations were observed in the cases in which histologic examination revealed severe dysplasia or a carcinomatous component. These anomalies are discussed in relation to those described in colorectal adenocarcinoma.

Adenocarcinoma↗

Circulating levels of colony-stimulating factor 1 as a prognostic indicator in 82 patients with epithelial ovarian cancer.

Serum samples from 82 patients with epithelial ovarian cancer, previously assayed for CA125, were assayed for circulating colony-stimulating factor 1 (CSF-1). An elevated CSF-1 concentration (> 450 U ml-1 or > 5.42 ng ml-1) was significantly associated with a worse survival (P = 0.02). The predictive value of raised CSF-1 levels was retained whether the first available sample for all patients (n = 82) or the first sample at the start of chemotherapy (n = 41) was considered. Mean CSF-1 levels (n = 14) dropped significantly during six courses of platinum-based chemotherapy (P = 0.02). Although an elevated CA125 concentration appeared to be a prognostic indicator in the total population (n = 82), it was not related to prognosis in the group of patients from whom samples had been drawn at the start of chemotherapy. In a Cox proportional hazards model, CSF-1, but not CA125, was significantly associated with outcome following adjustment for stage, grade and degree of surgical clearance.

Adenocarcinoma↗

[Immunoradionuclide localization of human neuroblastoma xenografted in nude mice using anti-GD2 labelled with I125].

Neuroblastoma is the most frequent tumour of the childhood under the age of 5. The staging and the follow up are achieved by MIBG scintigraphy, considered as the method of reference, but sometimes difficult to interpret . The availability of monoclonal antibodies against the ganglioside GD2, expressed on the cell membrane of neuroblastoma and neuro-endocrine cancers offers novel tools that deserve to be carefully explored. We investigated four mouse monoclonal antibodies (3 IgG3: BW704, 7A4, 60C3, and the IgG1 variant of BW704: MAK704), on nude mice xenografted with a human neuroblastoma (REM). Sixty one nude mice were included. The three former MAbs provided tumour imaging, the best results being obtained with BW704, followed by 7A4 and 60C3. MAK704 was disappointing. A control antiphosphorylcholine antibody (P51-1) did not give any tumour image in the three tested mice. Scintigraphy ratios tumour/liver and tumour/muscle reached 20 and 100 with BW704, respectively, on the 10th day. Good imaging quality was already obtained from the 24th h. The tumour uptake, calculated from radioactivity countings of resected samples, reached 22 +/- 3% of injected dose per gramme. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications.

Animals↗

Mammographically-detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity.

The new histologic classification proposed by Holland et al was applied to 127 cases of mammographically-detected ductal carcinoma in situ (DCIS). The relationship between histologic types and tumor cell expression of estrogen and progesterone receptors, p53 protein, c-erbB-2 oncoprotein, and proliferative activity markers was evaluated. There were 38 (30%) well differentiated, 39 (31%) intermediately differentiated and 50 (39%) poorly differentiated DCIS. Immunohistochemistry showed that 81% of the tumors were estrogen-receptor positive and 73% progesterone receptor positive. p53 protein and c-erbB-2 oncoprotein expression was identified in 40% and 57% of the cases, respectively. Growth-fraction determination with the Ki-67 antibody showed that 52% of the tumors had high proliferative activity. A highly significant association was found between the histologic types of DCIS and p53 protein, c-erB-b2 oncoprotein, and proliferative activity marker expression: these biological markers were more frequently overexpressed in less differentiated DCIS. No significant relationship with estrogen or progesterone receptor expression was noted. A strong relationship with the amount of tumor necrosis was also found. The clinical significance of these results should, however, be determined by long-term follow-up studies of patients with DCIS.

Adult↗

Adenomyoepithelioma of the breast: fine-needle sampling with histologic, immunohistologic, and electron microscopic analysis.

Fine-needle sampling was performed in a woman with a subareolar breast mass. The cytologic diagnosis was consistent with a benign sweat gland-type tumor. Cytologic features included epithelial cells and spindle-shaped cells lying free or in fibrillary myxoid ground substance. Histologic study revealed the biphasic appearance of this tumor composed of proliferating myoepithelial cells and glandular epithelial cells as supported by immunohistologic and electron microscopic analyses. Epithelial cells were strongly positive for cytokeratins, and spindle cells were positive for actin, S-100 protein, and keratin and showed ultrastructurally typical features of myoepithelial cells.

Biopsy, Needle↗

Paget's disease of the nipple without clinically and radiologically detectable breast tumor. Histochemical and immunohistochemical study of 44 cases.

Paget's disease of the nipple is a rare lesion nearly always associated with an underlying breast cancer, clinically impalpable and radiologically undetectable in about 40% of the patients. Fourty-four cases (28 mastectomies and 16 biopsies of the nipple) of Paget's disease of the nipple without clinically and radiologically detectable breast tumor were retrospectively studied by means of histochemistry and immunohistochemistry. Histochemical study showed that Paget cells were PAS positive and diastase resistant, and alcian blue positive at pH 2.5 in 32% and 18%, respectively. Immunohistochemical study showed that Paget cells were EMA and c-erbB-2 positive in 100% and 84%, respectively. Four of the six EMA positive and c-erbB-2 negative cases of Paget's disease of the nipple in which the underlying tumor could be pathologically analyzed were associated with ductal carcinoma in situ of cribriform or mixed types. These findings are helpful for differentiating Paget's disease from other lesions of the nipple, namely Bowen's disease and eczema which do not react with both antibodies, and from nipple adenoma which exhibits a positive staining with anti-EMA antibody and no reactivity with anti-c-erbB-2 antibody.

Adult↗

An experience of the use of radioactive plaques after failure of external beam radiation in the treatment of retinoblastoma.

The authors have reviewed the results of radioactive plaques in recurrent retinoblastoma after external beam radiation in 34 eyes. They give their results on ocular conservation and on the visual outcome and compare these results with other series previously published. They think radioactive plaques are an alternative to enucleation in recurrent retinoblastoma after external beam.

Brachytherapy↗

Human papillomavirus infection in esophageal squamous-cell carcinoma in western countries.

Recent studies have suggested that esophageal HPV infection could be a risk factor for esophageal squamous-cell carcinoma. The aims of our study were to assess the presence of HPV esophageal infection among French patients with esophageal squamous-cell carcinoma and to compare the prevalence of this infection among control patients exposed to similar known risk factors (alcohol and tobacco) and among non-exposed control patients. All patients had the following investigations: serum immunoglobulin level, T-lymphocyte subsets, cutaneous anergy test and endoscopy with biopsies from tumoral and normal areas. Three different methods were used for HPV-infection diagnosis: histological score, in situ hybridization intended for detection of HPV types 6, 11, 16, 18, 31 and 33, and dot blot intended for detection of HPV types 6/11 and 16/18. Five out of 12 patients with esophageal carcinoma had HPV esophageal infection. This infection did not result from impaired immune status. The most frequently observed types are HPV 16/18. None out of 17 exposed controls and only 1 out of 7 nonexposed controls had HPV esophageal infection (p less than 0.01). HPV infection may be implicated in the development of esophageal squamous-cell carcinoma in association with known risk factors.

Age Factors↗

Induction chemotherapy in advanced head and neck tumors: results of two randomized trials.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Antineoplastic Agents↗

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients].

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.

Antineoplastic Combined Chemotherapy Protocols↗

[Value an immediate histological study of the lymph nodes at the time of surgical treatment of cancer of the uterine cervix].

From 1978 to 1989, 500 external iliac lymph node dissections were carried out at the Institut Curie during surgery for cancers of the uterine cervix. The percentage of error of the histological study of the lymph node was 2.8%, including 13 false-negative findings and 1 false-positive. In 1.8% of cases (9), there were doubts as to lymph node invasion, and no confirmation was possible. The most frequent cause of error was the failure to recognize partial invasion of a lymph node. Fibrosis and necrosis secondary to preoperative radiation therapy make the intraoperative histological study more difficult.

Cervix Uteri↗

Survival and acquired genetic alterations in colorectal cancer.

To set the basis for a precise assessment of new therapeutic approaches, the prognosis of patients with colorectal cancer should be evaluated with the highest precision. The recent discovery, in tumor cells, of somatically acquired genetic alterations believed to be instrumental in tumor behavior may provide new independent prognostic factors. In the present study, the usual prognostic factors and a set of genetic alterations, i.e., Ki-ras mutations, DNA content, and allelic losses on chromosome 17p, 18q, 5q, and 1p, were investigated in 109 colorectal carcinomas. Univariate analysis for correlation with 5-year survival showed the following significant associations: histological staging (P less than 0.00001), preoperative serum carcinoembryonic antigen concentration (P less than 0.002), DNA content (P less than 0.009), and allelic loss on the short arm of chromosome 17 (P less than 0.002) and 1 (P less than 0.03). In multivariate analysis, only histological staging and allelic loss on the short arm of chromosome 17 were found to be independently associated with shorter survival (P less than 0.0001 and P less than 0.004, respectively). Loss of 17p alleles in colorectal carcinoma thus appears to be a marker of tumor aggressiveness. Its monitoring may lead to an improved classification of patients when adjuvant chemotherapy is considered.

Aged↗