One-bloc percutaneous large biopsy of soft-tissue tumours: feasibility study and possible indications.

AIM: To report the early results of the Intact lesion excision system (LES) regarding feasibility, tolerance and efficiency in obtaining soft-tissue tumour samples under ultrasound guidance. MATERIALS AND METHODS: The feasibility and tolerance of Intact LES procedures under ultrasound guidance were studied prospectively in 15 patients. The procedure was performed on an outpatient basis under local anaesthesia by a single interventional radiologist with 6 years of experience and lasted around 30 min. RESULTS: The feasibility of the Intact LES for soft-tissue masses was good except when lesions were hard and calcified. Tolerance was good, with median pain experienced during the procedure evaluated at 4.5/10 (SD 2.2) and median post-procedural pain at day 1 evaluated at 1.8/10 (SD 2.5). No major complications were observed; however, for vascularised lesions, one case of acute wound bleeding and two post-procedural haematomas led to delayed pain. CONCLUSION: Percutaneous biopsy of suspected soft-tissue sarcoma using the LES device under ultrasound guidance is well tolerated and feasible. After a first non-contributing core biopsy, and especially, in the case of lipomatous lesions, it is a valuable option to consider, as is surgical incision biopsy.

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma.

The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC.

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome.

BACKGROUND: (18)Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. METHODS: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. RESULTS: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were confirmed in the independent cohort of 127 cancer patients. CONCLUSION: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H(+) symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Indications of external beam radiation therapy in non-anaplastic thyroid cancer and impact of innovative radiation techniques.

BACKGROUND: The mainstay of treatment for differentiated thyroid carcinomas is surgery. There is hardly any room for radiation therapy in differentiated thyroid carcinomas. We aimed to update recommendations for RT in the context of histological variants, increased use of radioiodine and new irradiations techniques. MATERIALS AND METHODS: A search of the French and English literature was performed using thyroid carcinoma, radiation therapy, surgery, variants and radioiodine. RESULTS: Papillary, follicular, Hürthle and medullary carcinomas represent about 80%, 11%, 3% and 4% of all thyroid carcinomas, respectively. Ten-year survival rates for patients with papillary, follicular and Hürthle cell carcinomas are 93%, 85%, and 76%, respectively. The occurrence of criteria such as older age (45 or 60 years-old), massive primary disease, extensive extracapsular spread and macroscopic iodine-negative components inconsistently indicate external beam irradiation (EBRT). The impact of EBRT on poorer-prognosis histological variants is an emerging issue. Noteworthy, the incidence of laryngeal and wound healing complications has been an important limitation to EBRT. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumor coverage and organ sparing such as the larynx, thus reducing late toxicities to less than 5%. Iodine contrast agents should be avoided during 4-6 weeks before radioiodine. PET CT is increasingly used in iodine-negative tumors. CONCLUSION: There are elective indications for EBRT and IMRT has the potential to improve local control.

Chemoradiation in anaplastic thyroid carcinomas.

BACKGROUND: ATC represents 1-2% of all thyroid carcinomas. Median survival is poor (3-10 months). Our goal is to update recommendations for RT in the context of new irradiation techniques. MATERIALS AND METHODS: A search of the French and English literature was performed with terms: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy and surgery. Level-based evidence remains limited in the absence of prospective studies and the small size of retrospective series of this rare tumor. RESULTS: Surgery when possible should be as complete as possible but without mutilation given the 8-month median survival of ATC. It should be followed by systematic chemoradiation in ATC. Initiation of treatment is an emergency given fast tumor doubling time. The most promising results of chemoradiation to date have been shown in series of radiation therapy (+/- acceleration) combined with doxorubicin +/- taxanes or cisplatin. Adjuvant chemotherapy (doxorubicin, cisplatine and/or taxane-based) may also be recommended given the metastatic potential of ATC and warrants further investigations. Data on neoadjuvant chemotherapy are missing. Intensity modulated radiation therapy offers clear dosimetric advantages and has the potential to improve tumor and nodal (posterior neck, mediastinum) coverage, i.e., locoregional control while optimally sparing the spinal cord, larynx, parotids, trachea and esophagus. PET-CT and MRI may be used for RT planning. CONCLUSION: Chemoradiation with debulking surgery whenever possible is the mainstay of treatment of anaplastic thyroid carcinomas (ATC). EBRT using IMRT has the potential to improve local control. Taxane-doxorubicin concomitant chemoradiotherapy is worth further investigation.

Prognostic impact of tumour multifocality in thyroid papillary microcarcinoma based on a series of 160 cases.

OBJECTIVE: The objective of this study was to evaluate the prognostic impact of tumour multifocality in papillary thyroid microcarcinoma (PTMC). METHODS: All patients who underwent total thyroidectomy and central neck dissection for PTMC in our institution between 1990 and 2007 were included in this retrospective study. Statistical correlations between tumour multifocality and various clinical or pathological prognostic parameters were assessed by univariate and multivariate analyses. RESULTS: A total of 160 patients (133 women and 27 men; mean age: 47.8±13.7 years) were included in this study. Tumour multifocality was demonstrated in 59 (37%) patients. Central neck metastatic lymph node involvement was identified in 46 (28%) patients. No statistical correlation was demonstrated between tumour multifocality and the following factors: age, gender, tumour size, extension beyond the thyroid, metastatic central neck lymph node involvement and risk of recurrence. A tumour diameter greater than 5mm was associated with a higher risk of recurrence (P=0.008). CONCLUSION: Tumour multifocality does not appear to have a prognostic impact in PTMC.

[Publication of biological samples collections catalogues by tumor banks]. / La publication de catalogues de collections d'échantillons biologiques par les tumorothèques.

Biobanks in general, and specifically tumour banks, are considered as essential tools for the development of translational and clinical research in biology and oncology. Biobank tasks include the collection and preservation of biological samples, and their association with information that will be essential for further scientific use ("annotations" that allow for the "qualification" of biological samples in biological resource). A collection is made of a series of biological resource that are representative of a homogeneous group of individuals or patients that are defined on the basis of clinical or biological information. Collections are used by scientists that are aware of their existence. In the absence of a published catalogue, this awareness is most often limited to research teams that are geographically close, or to investigators who already established collaborative projects with medical teams within the hospital that operates the tumour bank. Publications of catalogues, especially digitalized and online catalogues, should foster the development of high-level, large-scale and multicentric scientific projects. In addition, tumour banks will formalize rules that allow publication of collections, and upstream, rules that are used to qualify biological samples in biological resource: this should translate in an improved overall quality of samples and annotations. Tumour bank catalogues remain relatively few; however, some recent achievements established the "proof of concept" and already raise questions regarding rules for publication. It will be important to demonstrate that these high expectations translate into measurable benefits.

[CyberKnife and neoadjuvant chemotherapy for breast tumors: preliminary results]. / CyberKnife et chimiothérapie néoadjuvante pour les tumeurs du sein localement évoluées : résultats préliminaires.

PURPOSE: CyberKnife((R)) (CK) allows stereotaxic irradiation for thoracic tumor thanks to a tracking system which potential is known for lung tumors. This technique has never been used to treat breast tumors but may have a real potential. PATIENTS AND METHOD: In order to define the interest of treating breast tumors with CK, we have conducted a phase I study with a dose escalation, adding CK to neoadjuvant chemotherapy in view of allowing conservative treatment for patients that will not have surgery in first intent. Neoadjuvant chemotherapy includes six cures, including three of docetaxel and three of FEC. CK treatment is made during the second cure of chemotherapy. Two dose levels are delivered in three fractions: 19.5 and 22.5Gy. Surgery is performed six to eight weeks after the last cure. The primary objective is to define tolerance of stereotactic irradiation concomitant with neoadjuvant chemotherapy for breast tumors. Skin toxicity is the limiting criterion of the study. The secondary objectives are both histological response and quality of surgery. Here, we are presenting the preliminary results of the 2-dose level. This study participates in the French national grant called Programme hospitalier de recherche clinique (PHRC). RESULTS: No skin toxicity of grade I or more have been find. Surgery was performed as conventional and there was no complication. Pathology exams found one complete response, one lymphangitis and one partial response. CONCLUSION: These preliminary results seem to be promising but need to be confirmed. We carry on the dose escalation study.

[Papillary thyroid microcarcinomas: review of 230 cases]. / Les microcarcinomes papillaires de la glande tyroïde: à propos de 230 cas.

OBJECTIVES: Papillary microcarcinoma (PMC) is one of the most frequent pathological forms of thyroid cancer Here, we describe the circumstances of diagnosis and the clinical and pathological characteristics of this tumour We also analyze the therapeutic management and compare it with the recent published guidelines. METHODS: Between 2000 and 2006, a total of 230 patients with a PMC of the thyroid gland were included in this retrospective study. We have investigated the correlations between some pathological parameters (plurifocality, lymph node invasion...) and several factors (age, gender, tumour size...). RESULTS: The diagnosis of PMC was suspected in the preoperative period in 15% of the patients, and was confirmed intraoperatively by the pathologist in 42% of the cases. Plurifocal or bilateral PMC were discovered in respectively 30 and 17% of the patients. The rate of lymph node invasion in the central neck (level VI) was 26%. An elevated tumor size was correlated with a higher rate of plurifocal or bilateral PMC and of lymph node metastasis (p < 0.05). The indications for postoperative radioiodine therapy were reduced by approxiately 50% in the second part of our study. There were no case of thyroid PMC-related death. CONCLUSIONS: Even for these small tumours, tumour size remains correlated with the tumour aggressiveness. The place of radioiodine therapy in the management of thyroid PMC was progressively reduced because of the good prognosis of this tumour.

Prognostic factors in 1,038 women with metastatic breast cancer.

BACKGROUND: Treatment of metastatic breast cancer (MBC) remains palliative. Patients with MBC represent a heterogeneous group whose prognosis and outcome may be dependent on host factors. The purpose of the present study was dual: first, to draw up a list of factors easily available in everyday clinical practice requiring no sophisticated or costly methods and second, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. PATIENTS AND METHODS: From 1975 to 2005, a total of 1,038 women with MBC during their follow-up were included in this retrospective analysis. Patients were subsequently assigned to five groups according to the period of metastatic diagnosis. RESULTS: It is shown that age at initial diagnosis, hormonal receptor status and site of metastasis are the most relevant prognostic factors for predicting survival from the time of metastastic occurrence. It is also shown that a metastasis-free interval is an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease. CONCLUSION: These fundamental observations may assist physicians in evaluating the survival potential of patients and in directing them toward the appropriate therapeutic decision.

Very Late Local Relapse of Ewing's Sarcoma of the Head and Neck treated with Aggressive Multimodal Therapy.

Ewing's sarcoma's relapse rarely occurs more than two years after the initial diagnosis. We report the case of a 26-year-old man with a history of Ewing's sarcoma of the left maxillary sinus at the age of 10 who presented with a very late local relapse, 16 years after the first occurrence of disease. Ultimate control was achieved after multimodal therapy including surgery, high-dose chemotherapy, and radiotherapy. This report indicates that local relapses of Ewing's sarcoma can be treated with curative intent in selected cases.

[When should caution be used with regards to histopathologic findings of imaging-guided breast micro- and macro-biopsies?]. / Quand se méfier des résultats des micro et macrobiopsies guidées mammaires?

The development of imaging-guided biopsy techniques has considerably improved the early diagnosis of breast cancers following initial detection by screening. Nevertheless, in a small percentage of cases, histopathologic findings are unsatisfactory owing to false negative errors attributable to operator inexperience or inadequate sample material (this is especially true for microcalcifications with 20% underestimation rates for atypical hyperplasia); repeat biopsy is warranted in such situations. When a discrepancy exists with imaging findings and for cases of atypical epithelial hyperplasia, surgical excision is imperative so as not to overlook or underestimate a malignant lesion. Controversy continues concerning the best approach for radial scars (sclerosing ductal lesions), papillary lesions, atypical lobular hyperplasia and lobular carcinoma in situ: determination of which benign anomalies can merely be followed-up remains a problem. Better awareness of the limitations of percutaneous tissue sampling procedures should lead to refinement of the indications for these techniques and improvement of patient selection and thereby reduce delays in accurate diagnosis.

Early versus late local recurrences after conservative treatment of breast carcinoma: differences in primary tumor characteristics and patient outcome.

OBJECTIVES: To investigate whether some aspects of patient or tumor characteristics influence the timing of local recurrence (LR) in breast cancer treated conservatively, and to assess the impact of the timing of LR on patient outcome. METHODS: A retrospective analysis was conducted on patients treated with conservative breast surgery followed by radiotherapy for breast carcinoma who developed LR. Out of 2,008 cases treated in our Institute between 1977 and 2002, 180 ipsilateral LR were observed. Of these, 46 LR were observed within 36 months after treatment, called early local recurrence (ELR), 44 developed between 37 and 60 months, called medium local recurrence (MLR), and 90 occurred after 60 months, called late local recurrence (LLR). Patient and tumor characteristics were analyzed in the 2 groups and compared. RESULTS: Primary tumors >20 mm were more frequently found in patients with ELR (31%) than in patients with LLR (17%, p = 0.047). Grade 3 tumors were more often encountered in patients with ELR than in patients with LLR (27 versus 7%, p = 0.0002). Patients with ELR more frequently had tumors with negative estrogen receptors than patients with LLR (37% versus 6%, p < 0.0001). There was no statistically significant difference in the axillary lymph node (LN) status between patients with ELR and those with LLR (35 and 23% of positive LN, respectively, p = 0.24). Tumor size, grade, LN status, hormone receptors and the timing of LR affected the specific survival (SS) from initial surgery. On multivariate analysis, only LN status and the timing of LR retained an independent prognostic value, with an odds ratio of 6.7 for ELR. After LR, the SS was also influenced by all of the above factors, and on multivariate analysis, LN status, hormone receptors and the timing of LR were independent predictors with an odds ratio of SS of 2.50 in case of ELR (p = 0.006). The 5-year SS after LR for ELR, MLR and LLR were 55.8, 74.8 and 79.5%, respectively. CONCLUSIONS: Unfavorable tumor characteristics such as big size, high grade, lack of hormone receptors, but not LN status, were associated with ELR. These findings suggest that patients with such aggressive tumor characteristics who do not recur early will have a lower risk of LLR than patients with more favorable factors.

[Guillain-Barré syndrome and non-Hodgkin's lymphoma. Report of one case and review of literature]. / Syndrome de Guillain-Barré et lymphome non-hodgkinien. A propos d'une observation et revue de la littérature.

Patients with lymphoma frequently develop neurologic abnormalities mainly due to nervous system infiltration but also direct drug toxicity. Moreover Guillain-Barré syndrome (GBS) remains a possible neuropathy, rarely described in non-Hodgkin's lymphoma. We describe a case of GBS in a patient with non-Hodgkin's high grade lymphoma. A 74-year old man with a newly diagnosed stage I high-grade lymphoma (precursor B-cell Burkitt like type according to the R.E.A.L. Classification) develop flaccid quadriparesis, 7 days after the end of the third course of CHOP treatment. The clinical course and neurological examination were consistent with GBS. The patient was in tumoral complete response. Despite appropriate treatment and a transfer in a reanimation unit, the patient died 3 days after the beginning of neurologic symptoms. The low number of cases described in the international literature doesn't permit to understand the association of this neurologic disease with non-Hodgkin's lymphoma. Collecting more data could lead interesting information to know the place of malignant hematological disease in the natural history of GBS.

P53 determination alongside classical prognostic factors in node-negative breast cancer: an evaluation at more than 10-year follow-up.

BACKGROUND: There is heterogeneity of methods and conflicting results concerning the prognostic value of p53 in node-negative breast cancer. The clinical value of a quantitative method for measuring tumoralp53 content still needs to be evaluated. PATIENTS AND METHODS: A long-term retrospective study was conducted on 297 node-negative patients with a median follow-up greater than 10 years (11 years, 101-172 months). Classic prognostic factors were considered including age, tumor size, histoprognostic grade and estradiol (ER) and progesterone receptors (PR). In addition, the value of p53 determination (immunoluminometric assay in tumor cytosol) was assessed for this long follow-up period. RESULTS: p53 concentrations were significantly linked to the histological grade (P = 0.001), to tumor size (P = 0.02) and ER status (P = 0.01). Higher p53 tumoral concentrations were found in tumors with large size, pejorative histological grade and negative ER status. In contrast, p53 tumoral concentrations were not influenced by menopausal or PR status. Multivariate Cox analysis demonstrates that tumor size was the only significant predictor of disease-free survival (P = 0.049) with a risk factor at 1.38. As regards specific survival, univariate Cox analysis indicates that p53 taken as a continuous variable is a significant predictor (P = 0.024) together with histological grade, tumor size and ER status. In a multivariate Cox analysis there were two significant and independent variables for predicting overall survival: tumor size (P = 0.031) and, ER status (P = 0.015) with the highest risk factor (RR = 2.14). CONCLUSIONS: The present investigation points out that the prognostic power of p53 tumor determination evaluated at more than 10 years median survival is not higher than the well-recognized classic prognostic factors in node-negative breast cancer. The present data highlight the need to assess the prognostic value of potentially new biological factors in node-negative breast cancer on cohorts of patients followed over periods in excess of 10 years.

Application of an original RT-PCR-ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients.

The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil-epirubicin-cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28-79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection (beta2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg(-1)) up to 35.71 ng mg(-1) (mean 1.18, median 0.13 ng mg(-1)). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r= -0.27). P53 was not linked to progesterone receptor (PR) status, S phase fraction, or MRP Significantly greater MDR1 expression was observed in grade I tumours (P = 0.029). No relationship was observed between MDR1 and MRP. Neither MDR1 nor MRP was linked to ER or PR status. Unlike MDR1, MRP was correlated with the S phase: the greater the MRP, the lower the S phase (P = 0.006, r = -0.42). Univariate Cox analyses revealed that MDR1, MRP, p53 and S phase had no significant influence on progression-free or specific survival. A tendency suggested that the greater the p53, the shorter the progression-free survival (P = 0.076 as continuous and 0.069 as dichotomous).

[Immunohistochemical evaluation of the in vitro bromodeoxyuridine labeling index. 236 breast cancers studies by image analysis]. / Evaluation immunohistochimique de l'index de marquage après incorporation in vitro de bromodéoxyuridine. A propos de 236 cancers mammaires étudiés par analyse d'image.

We studied with computerized image analysis 236 breast cancer samplings after in vitro bromodeoxyuridine incorporation and immunohistochemical revelation. Labeling index values were compared with the usual prognostic factors and with the other studies in the literature. We established a positive correlation between labeling index and tumor size, histoprognostic grading, phase S and DNA index. A high labeling index was correlated with the absence of hormonal receptors but not correlated with the other prognostic factors. These results on tumor kinetics are similar to those obtained by flow cytometry and from other studies in the literature. However, this technic using optical microscopy allows for reliable selection of tumoral cells. Furthermore, the semi-automated image analysis provides an objective and reproducible evaluation of the labeling index.

Study of the frequencies of CYP1A1 gene polymorphisms and glutathione S-transferase mu1 gene in primary breast cancers: an update with an additional 114 cases.

We studied the polymorphisms m1 (Msp1 restriction site) and m2 (codon Val substitution) of CYP1A1 gene and the copy number of glutathione S-transferase mu1 (GSTM1) gene on 487 DNA of breast cancer primary tumours from Caucasian group. Tumours of patients aged 55 years and under at diagnosis presented a great proportion of wild m1 (-/-) genotype; 83.6% vs. 69.5% (p < 0.0006), and a higher percentage of copy number of GSTM1 equal or under one copy; 65.2% vs. 53.4% (p < 0.011) for older patients m1 and m2 variants are closely linked (p < 0.0000). Tumour with a low copy number of GSTM1 is correlated with high histological grading (p < 0.01) and high Cathepsin D concentrations (p < 0.02). The combinations of different genotypes showed that association wild m1 (-/-) genotype and copy number of GSTM1 inferior or equal to one copy is correlated with an early onset of breast cancer primary tumour 44% vs. 6.4% for m1 (-/+) or (+/+) genotype and copy number of GSTM1 superior to one (p < 0.0000). The CYP1A1 gene wild form seems to be associated with early cancer development in Caucasian patients.

[Malignant nasosinusal melanomas. Review of the literature apropos of 12 cases]. / Les mélanomes malins nasosinusiens. Revue de la littérature à propos de 12 cas.

Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses remains a scarcely encountered malignancy and we report 12 cases of our own experience from 1991. These mucosal melanomas occur mainly in the elderly and present most commonly as a one sided airway obstructive syndrome with often bleeding in the nasal cavity. No sex or race ratio is found. Histological examination of the surgical specimen has been made easier since the use of immunohistochemical studies. The original site of onset is commonly located at the inferior part of the nasal cavity but in many cases, it is noted several sites of tumor localization. Despite well conducted treatment the prognosis remains quite deceiving and significantly poor. In our study, the 4-year actuarial survival was 26%. The 5-year survival rate ranges in the literature from 10% to 40%. Short and long term follow-up show an important rate of recurrence (local and lymph node metastases as well as distant metastases). The insidious evolution of the malignancy usually happens during the first year. Computed tomography and MRI are essential in the evaluation of tumor extension. The treatment is based on the combination of surgery and radiotherapy: Surgery is practised first and must ensure sufficient excision of the tumor without minimal functional or aesthetic damage in this complex region. This surgery is based on surgical approaches to the midface known as Lateral rhinotomy and midfacial degloving. When there is cervical lymph node involvement at the time of diagnosis it is suitable to treat it, even in case of recurrence. Complementary high dose radiation is required to treat tumors which could not undergo surgery and also as adjuvant therapy after removal of the mass.

Cell cycle expression of p53 protein, c-Myc gene product and tyrosine-phosphorylation level determined by image analysis in human breast cancer cells.

OBJECTIVE: To investigate the cell cycle expression of p53 protein, c-myc gene product and tyrosine phosphorylation level in human breast cancer cells. STUDY DESIGN: Using a multifluorescence imaging procedure, the concentration per cell in different phases of the cell cycle can be evaluated by analyzing the bivariate contour plot of DNA content versus antigen concentration. RESULTS: Low fluorescence intensity was observed in the G0/G1 phase for the three markers. The analysis of individual cells demonstrated that approximately 10% of cells were negative. During the G1/S transition, the fluorescence intensity of the three antigens increased rapidly. However, after the mild S-phase, the increase of c-myc was more marked than the tyrosine phosphorylation level, whereas p53 protein remained stable, with a slight tendency to decrease. CONCLUSION: This study confirmed that the p53 protein and c-myc gene product could perform a regulatory function in G1/S transition and, consequently, may play an important role in malignant transformation. Like-wise, the variations of tyrosine kinase activity were linked to cellular progression throughout the cell cycle and could be a useful marker of alteration in the growth-factor signaling pathway. Thus, the multifluorescence imaging procedure may provide useful information on the mechanisms of the cell cycle and on malignant transformation.