Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. METHODS: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. RESULTS: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. CONCLUSION: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

Can c-myc amplification reliably discriminate postradiation from primary angiosarcoma of the breast?

PURPOSE: Breast angiosarcomas are rare vascular malignancies that arise secondary to irradiation or de novo as primary tumours. The aim of this study is to know whether c-myc amplification can reliably discriminate these two entities. MATERIEL AND METHODS: Forty-seven patients treated for breast angiosarcomas were studied. Thirty-two patients were diagnosed with postradiation angiosarcomas after breast cancer treatment and 15 patients with primary angiosarcomas. Interphase fluorescence in situ hybridization (FISH) was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections. RESULTS: Amplification (5- to 20-fold) of the c-myc oncogene was found in all breast radiation-induced angiosarcomas (32 tumours) but in none of the 15 primary angiosarcomas except one (7%). CONCLUSION: This study reinforces that there are true pathogenetic differences between the two types of breast angiosarcomas which are morphologically indistinguishable. These data point the pathways preferentially involved in the pathogenesis of post radiation angiosarcomas of the breast and may provide the basis for an additional targeted therapy.

Clinico-pathology and prognosis of endometrial cancer in patients previously treated for breast cancer, with or without tamoxifen: a comparative study in 363 patients.

OBJECTIVE: To compare the clinic-pathologic variables and the prognosis of endometrial cancer in patients with and without previous breast cancer, with and without Tamoxifen. METHODS: We analyzed patients treated for an endometrial carcinoma from 1994 to 2004: patients without breast cancer (group 1), patients with a previous breast cancer without tamoxifen (group 2) and patients treated for breast cancer with tamoxifen (group 3). Survival rates were calculated according to Kaplan-Meier method and compared using a Log rank test, multivariate analysis was performed with a Cox regression model. RESULTS: 363 patients were analyzed. 80 patients had a previous history of breast cancer (43 received tamoxifen). Although it was not statistically significant, more carcinosarcomas were observed in patients in group 3 than patients in groups 1 and 2 (11.7% versus 4.2% and 5.4% respectively, p = 0.17).) Median follow-up was 87 months [2-185]. 5-year overall survival rate was respectively in groups 1, 2 and 3: 82%, 73.2%, and 61% (p = 0.0006). 5-year local relapse-free survival rate was respectively: 95.9%, 93.1% and 82.5% (p = 0.02). In multivariate analysis, factors affecting overall survival rate were: age ≥65 ans (HR 3.62, p < 0.0001), FIGO stage (HR 3.33 p < 0.0001 for locally advanced stage versus early stage, HR 8.87 p = 0.03 for distant extension versus early stage), and group 3 (HR 2.83 p < 0.001 versus group 1). CONCLUSION: Patients with endometrial cancer previously treated for breast cancer show a worse prognostic, particularly if they reveived tamoxifen.

Histological grade concordance between diagnostic core biopsy and corresponding surgical specimen in HR-positive/HER2-negative breast carcinoma.

BACKGROUND: The identification and validation of suitable predictive and prognostic factors are a challenge to improve the treatment scheme selection. Discordances in histological grade can be established between core biopsy and surgical specimens. This is important in HR-positive/HER2-negative subgroup where histological grade identifies patients at high risk and is a strong determinant for treatment scheme. METHODS: A total of 350 consecutive invasive breast carcinoma biopsies were assessed and compared with surgical specimens in Institut Curie, Paris, France. Clinical, radiological and pathological data were recorded. RESULTS: Histological grade concordance rate in the HR+/HER2- group was 75%. A grade underestimation was mainly due to mitotic index misgrading (23%). Large tumours (P<0.05), premenopausal patients (P=0.005) and non-ultrasound-guided biopsies (P=0.04) were risk factors for misgrading. The highest discordance was found in tumours that required chemotherapy (39%, P<0.05), and it was related to an underestimation of histological grade on core biopsies (94%). CONCLUSIONS: Histological grade in HR+/HER2- group is important to identify patients with poor prognosis and start a systemic therapy. Histological grade discordance was correlated with an underestimation of mitotic index and factors probably associated with intratumor heterogeneity (premenopausal status, tumour size and the type of core biopsy performed). But such discordance did not appear to modify the therapeutic decision, because systemic treatment decision-making also integrates other variables. Determining histological grade in core biopsy can be especially important in HR-positive/HER2-negative subgroup where it identifies patients at high risk and is a strong determinant of the treatment scheme.

Uveal metastasis revealing lung cancer.

BACKGROUND: Uveal metastases (UM) are the most common intraocular malignancies and can be the first manifestation of a disseminated disease. The purpose of this study is to determine the frequency with which uveal metastasis results in a diagnosis of lung cancer, to describe the clinical characteristics of patients with lung cancer metastatic to the uvea, as well as diagnostic difficulties that may be encountered. PATIENTS AND METHODS: We carried out a single-center retrospective study of the medical records of all patients who presented with a UM between 1999 and 2010 at the institut Curie in Paris. From these patients, we retrospectively studied UM secondary to lung cancer. A work-up including thoracic-abdominal-pelvic CT was performed for each patient in whom the primary source of choroidal metastasis was unknown. RESULTS: Of 109 patients presenting with UM, 43 were diagnosed with primary lung cancer (39.4%). Of those 43 patients, the UM was observed prior to the lung cancer in 31 patients (72.1%). Demographic data included 61% male and 39% female, mean age 59.1 years (range: 31-78), and mean life expectancy after diagnosis of UM was 7.5 months (range: 0.7-29). Other metastatic sites were associated with UM in 90.7% of the patients. In all, 90.7% of the patients presented with blurred vision, and 25.6% with pain or inflammation. UM were located within the choroid for 39 patients (90.7%), the iris for three patients (7.3%) and the vitreous for one patient. Seventy percent of patients had a solitary lesion, 76.7% had unilateral involvement, and 23.3% of cases were bilateral. Mean thickness on B-scan ultrasonography was 3.61 mm (range: 1-8.5 mm). In all, 81.4% of UM were unpigmented, while 18.6% showed pigment mottling. In all, 20.9% of patients were referred with the diagnosis of choroidal melanoma from their regular ophthalmologist, and three of the 43 patients (6.9%) were initially misdiagnosed and treated for melanoma at Curie. Chest X-ray was unremarkable in 18.9% of patients. CONCLUSION: UM is often the first manifestation of disseminated disease and requires a search for the primary tumor, in particular lung cancer. Standard chest X-ray cannot rule out the diagnosis. Metastases may be solitary with heterogenous pigmentation, and the differential diagnosis from uveal melanoma may be difficult, requiring the expertise of a referral center.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution.

OBJECTIVE: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX.

BACKGROUND: Colorectal cancer (CRC) patients whose tumours have microsatellite instability (MSI) do not benefit from adjuvant 5-fluorouracil. However, the predictive value of MSI is not known for FOLFOX, now recommended in adjuvant setting. PATIENTS AND METHODS: MSI phenotype was assessed by the pentaplex method. Three-year relapse and disease-free survival (DFS) of patients treated for CRC with FOLFOX 4 in an adjuvant setting were compared according to MSI phenotype. RESULTS: A total of 105 patients (19 MSI, 86 microsatellite stable, MSS) were included. Stage II patients more frequently exhibited MSI (58%) than MSS (21%); (p=0.002). Patients with MSI relapsed significantly less than those with MSS (10.5% vs. 35.0%; p=0.04). DFS was similar for MSI and MSS (p=0.1). In univariate analysis, stage (p=0.0006) and MSI status (p=0.017) were significant predictors of DFS. CONCLUSION: MSI status was associated with significantly fewer relapses and a better prognosis. FOLFOX4 did not alter survival of patients with MSI and can be administered to them.

Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer.

BACKGROUND: Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer. PATIENTS AND METHODS: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria. RESULTS: Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients. CONCLUSION: No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.

[Prognostic factors for malignant uveal melanoma. Retrospective study on 2,241 patients and recent contribution of monosomy-3 research]. / Facteurs pronostiques du mélanome malin de l'uvée. Etude rétrospective sur 2,241 patients et apport récent de la recherche de la monosomie 3.

INTRODUCTION: We conducted a retrospective study on the clinical factors influencing the local and general prognosis of patients treated for uveal melanoma with a preliminary analysis of the prognostic value of monosomy 3. PATIENTS: and method: The patients sent to Curie Institute for uveal melanoma have a complete initial clinical evaluation, conservative management by radiotherapy or enucleation, and local and general long-term follow-up. Over the last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors of enucleated patients. Findings concerning the initial workup, treatment, and follow-up are recorded prospectively. We conducted a retrospective study with multivariate analysis of the clinical factors influencing local recurrence, ocular conservation metastasis, and survival and studied the effect of monosomy 3. RESULTS: A total of 2241 patients were registered with a median follow-up of 72 months. Of these patients, 92.8% had conservative management with iodine 125 brachytherapy or proton beam therapy and 7.2% of the patients had enucleation (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The clinical factors influencing survival were the size and location of the tumor, age of the patient, gender, and initial treatment. The factors influencing the metastatic risk were the same plus retinal detachment and local recurrence. Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION: This study found the usual risk factors with the difference that location on the equator seems to be of worse prognosis than ciliary body involvement for survival and metastasis. In addition, the initial retinal detachment appears to be a risk factor for local recurrence and metastasis. At present, the evaluation of chromosome 3 is available for enucleated tumors but it could probably be done on needle biopsy performed during conservative management as well. CONCLUSION: This study confirms previous results on the prognostic factors of uveal melanoma and on the value of monosomy 3. The increasingly precise identification of a group of high-risk patients should allow us to propose adjuvant therapy and to adapt follow-up.

[Cavitary choroidal melanoma in a child]. / Mélanome choroïdien kystique chez une enfant.

Uveal melanoma is very rare in children, and in both adults and children it can in rare cases develop intralesional cavities resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in differentiating cavitary melanoma from a benign cyst. We report the case of a 5-year-old girl who presented with a large intraocular pigmented mass in the left eye, showing multiple hollow cavities on ocular ultrasonography, CT scan, and MRI. The patient was treated by enucleation and the pathology confirmed the diagnosis of choroidal melanoma. FISH revealed no aberration in chromosome 3.

[Bilateral uveal melanomas. Five case reports]. / Le mélanome malin bilatéral de l'uvée. A propos de 5 cas.

PURPOSE: Uveal malignant melanoma is the most common primary intraocular tumor in adults. The occurrence of bilateral uveal melanoma is an extremely rare event, but the observed frequency is nevertheless higher than what can be attributed to chance. Possible responsible factors may include a genetic predisposition. PATIENTS AND METHODS: This retrospective study investigated the charts of patients examined from July 1988 to July 2001. For each patient, the clinical characteristics of the tumor (diameter, thickness, location), treatments, and results were noted, as were the eye involved, the presence of ocular melanocytosis, cutaneous melanoma, and second primary cancers. The information was then subjected to statistical analysis. RESULTS: Of 2 461 patients with unilateral primary uveal melanoma, five were identified as having bilateral uveal melanoma (0.2%). The expected number of cases would be less than one, hypothesizing an incidence of second melanoma identical to the incidence of a primary melanoma in the general population. The interval between the diagnosis of first and second primary uveal melanomas ranged from 0 to 6 years (median, 2 years). There was no clinical evidence of ocular melanocytosis in any of the five patients. The uveal melanoma was choroidal in three patients and affected the ciliary body or iris and choroid in two patients. DISCUSSION: The discrepancy between the estimated incidence (thought by Shammas to be one case every 18 years) and the observed incidence of bilateral primary uveal melanoma could be the result of many possible factors. An increased incidence of unilateral uveal melanoma could be a cause but in fact the incidence of uveal melanoma seems stable. Uveal melanoma may have been misdiagnosed in earlier years. The presence of a genetic predisposition to uveal melanoma is a possible explanation (suspected because of bilateral cases, familial cases and association with other primary malignancies). Ocular melanocytosis, which is described as more common in patients with bilateral uveal melanoma, was not seen in our series. CONCLUSION: Bilateral primary uveal melanoma occurs more frequently than expected. Unidentified germline mutations may be involved in pathogenesis. These cases serve as a reminder of the of the importance of careful examination of the second eye.

Consistent DNA losses on the short arm of chromosome 1 in a series of malignant gastrointestinal stromal tumors.

Fourteen malignant gastrointestinal stromal tumors (GISTs), characterized by immunohistochemistry, were analyzed by comparative genomic hybridization (CGH). The most striking feature was the detection of consistent DNA losses on the short arm of chromosome 1 in these 14 malignant tumors. Additional recurrent imbalances were also found: significant gains, which could be indicative of tumor progression, were frequent on the long arm of chromosome 1, as were losses of DNA copy number detected in chromosomes 13, 14, 15 and 22.

Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group.

BACKGROUND: Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS: From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS: In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION: In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas.

Leiomyosarcomas and most malignant fibrous histiocytomas share very similar comparative genomic hybridization imbalances: an analysis of a series of 27 leiomyosarcomas.

Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS.

[Role of adjuvant therapy in uterine sarcoma: experience of the Curie Institute]. / Intérêt des traitements adjuvants dans les sarcomes utérins: expérience de l'institut Curie.

PURPOSE: Uterine sarcoma is a rare disease and survival is poor. From 1975 to 1995, 73 uterine sarcomas were treated at the Curie Institute, and we analysed prognostics factors of survival. PATIENTS AND METHODS: Seventy-one patients underwent primary surgery, in most cases a radical non conservative surgery and a lymphadenectomy. Every patient had an irradiation (external beam irradiation and/or brachytherapy), and 24 patients received adjuvant chemotherapy. We observed that youngest patients had more leiomyosarcomas and low histologic grade tumours. Median survival was 42 months, and 5-years survival and local control were 36 and 68% respectively. Pelvic recurrences were most often before 2 years. This series demonstrates the impact of adjuvant irradiation on local control. This impact was stronger if the tumour had a high histologic grade (p < 0.01). However, irradiation, as well as chemotherapy, had no impact on the survival. CONCLUSION: The study confirmed that irradiation enable a better local control. However modalities of radiation therapy (brachytherapy and/or external beam radiotherapy, dose, volume), are still controversed.

The RB1 gene is the target of chromosome 13 deletions in malignant fibrous histiocytoma.

Forty-four malignant fibrous histiocytomas (MFHs) were studied by comparative genomic hybridization. Among the observed imbalances, losses of the 13q14-q21 region were observed in almost all tumors (78%), suggesting that a gene localized in this region could act as a tumor suppressor gene and that its inactivation could be relevant for MFH oncogenesis and/or progression. We determined by CA repeat analyses a consensus region of deletion focusing on the RB1 region. The RB1 gene was then analyzed by protein truncation test, direct sequencing, fluorescence in situ hybridization, Southern blotting, and immunohistochemistry. RB1 mutations and/or homozygous deletions were found in 7 of the 34 tumors analyzed (20%). Among the 35 tumors with comparative genomic hybridization imbalances analyzed by immunohistochemistry, 30 (86%) did not exhibit significant nuclear labeling. The high correlation between chromosome 13 losses and absence of RB1 protein expression and the mutations detected strongly suggest that RB1 gene inactivation is a pivotal event in MFH oncogenesis. Moreover, the observation of a high incidence of MFH in patients previously treated for hereditary retinoblastoma fits well this hypothesis.

Loss of chromosome 13 is the most frequent genomic imbalance in malignant fibrous histiocytomas. A comparative genomic hybridization analysis of a series of 30 cases.

Regional chromosome localizations of DNA copy number imbalances were studied by comparative genomic hybridization in 30 malignant fibrous histiocytomas: 13 primary tumors (2 myxoid, 9 storiform pleomorphic, and 2 with more undifferentiated phenotype) and 17 local recurrences (2 myxoid, 11 storiform pleomorphic, and 4 with more undifferentiated phenotype). Abnormal comparative genomic hybridization (CGH) profiles were observed in 25 tumors (83%). The most frequent gains (ratio > 1.2) corresponded, by order of frequency, to entire Xp, and bands 1q21, 19q13.1, 19p13, 5p13-p14, 1p31, 17p, 18p, 20q, 1p35, 17q23, and 22q12. High levels of gains (ratio > 1.5) were recurrently detected for Xp (10 cases), and in bands 1q21-q22 (8 cases), 3q27 (4 cases), 5p13-p14 (3 cases), 13q32-q34 (3 cases), 15q22-q26 (3 cases), and 17p11-p12 (3 cases). Losses of 13q12-q14 or 13q21 were observed in a large proportion of tumors (17 cases), suggesting that a gene localized in this region could act as a tumor suppressor gene. Losses of 11q23, 2q32, 11p13, 10p, 1q4, 9p2, 16q12, 4q3, 10q25, 3p23, 2p24, and 12p were also recurrently observed. Taken together, these results provide an overview of chromosome imbalances present in MFH, which could be of use for diagnostic purposes. They point to various chromosome regions which may harbor genes important for malignant fibrous histiocytomas (MFH) oncogenesis and progression.

Uterine sarcomas: the Curie Institut experience. Prognosis factors and adjuvant treatments.

PURPOSE: With a retrospective study at a single institution, we propose to analyze the prognosis factors and adjuvant treatment for uterine sarcomas. MATERIALS AND METHODS: From 1975 to 1995, 73 uterine sarcomas were treated at the Institut Curie, corresponding to 61 T1, 5 T2, and 8 T4 tumors. Thirteen patients had metastatic disease at the time of diagnosis. The mean age was 58 years. In 71% of patients, the presenting sign was bleeding. This series consisted of 44% leiomyosarcomas (LMS), 19% endometrial stromal sarcomas (ESS), and 31% carcinosarcomas or mixed mesodermal sarcomas (MMS). For the grading classification, we used the classification of the Sarcoma Group of the French Federation of Cancer Centres for soft tissue sarcomas. Of the patients, 66% presented a high-grade tumor. RESULTS: The median overall survival was 42 months, with a 5-year survival of 45%. Histological grade, FIGO stage, histology types, and menopausal status were the four independent factors in multivariate analysis. Eighteen patients relapsed locally (25.7%), with 77% central pelvic sites. Patients with radiotherapy and ESS had better local control in multivariate analysis. Thirty-four patients developed metastases (48.6%), mainly pulmonary (58.8%). Eight patients presented with peritoneal disease. High grades and LMS had the worst survival without metastasis in multivariate analysis. CONCLUSION: This study validated our classification for sarcoma grading and confirmed the finding of worst prognosis for LMS and the importance of radiotherapy in local control.

Unusual clonal chromosomal evolution in a breast carcinoma and its lymph node metastasis in a patient with Down syndrome.

A cytogenetic study was performed on a primary breast carcinoma and its axillary lymph node metastasis from a 53-year-old patient with trisomy 21, a carrier of a constitutional der(21;21). A translocation t(X;21) and the loss of the other X chromosome were shared by all karyotypes from tumor cells. The primary tumor was hyperdiploid with several gains of whole chromosomes. In contrast, most cells from the metastasis shared several rearrangements and losses leading to a hypodiploid karyotype. No normal chromosome 17 was present; instead, an i(17)(q10) and a fragment, detected by chromosome painting and presumably corresponding to a rearranged 17p, were found. Immunostaining for p53 was strongly positive in the metastasis but not in the primary tumor, suggesting a mutation of the TP53 gene in the metastasis. Finally, a small cell population of the metastasis was hyperdiploid like the clone in the primary tumor, suggesting that the node was colonized twice, at an early stage and a later stage of the clonal evolution of the tumor.