A specific breast cyst fluid protein was purified by the following steps: ultracentrifugation, gel filtration, DEAE and Con A chromatography, and gel filtration with guanidine, 6 M. The protein was pure, having a molecular weight of 17,800 daltons on SDS-PAGE and 68,000 daltons on gel filtration. The GCDFP 17,800 is immunologically distinct from other breast cyst fluid components and known milk and plasma proteins. A specific radioimmunoassay was developed and used to determine GCDFP 17,800 in 158 samples of breast cancer cytosol. The GCDFP 17,800 levels were significantly different between grade I tumors (mean of 813 ng protein per mg +/- 430 SEM) and grade III tumors (mean 184 ng protein per mg +/- 59 SEM) and were correlated with progesterone receptor values in postmenopausal women (Spearman's correlation, p = 0.03) but not in premenopausal women. The value of GCDFP 17,800 did not differ between the pre- and the postmenopausal women. By immunocytochemistry the intracellular localization of the GCDFP 17,800 was also found in relation to tumor grading and in correlation with PR values. GCDFP 17,800 appears as a hormone-induced protein of the breast cells. Its intracellular detection by means of radiolabeling allows a more sensitive and precise evaluation of the hormone-dependence of the breast cancer cells and emphasizes the heterogeneity of the tumor cell population.
A specific protein from the liquid of a mammary cyst with a molecular weight of 15,000 (GCDFP 15) was studied in normal and pathological mammary tissue using an immunohistochemical method (peroxidase-anti-peroxidase complex). An immunoreactivity of the GCDFP type was found in normal idrosadenoid glands having an apocrine secretion. Histologically normal mammary tissue was not immunoreactive. In benign breast tissue the GCDFP was found particularly in epithelium undergoing apocrine metaplasia (55/55) and in atypical lobular epithelial hyperplasia (8/10). Of the adenocarcinomas of the breast 136/161 (84%) were immunoreactive, especially lobular carcinoma (13/13). The proportion of tumors with a high percentage of immunoreactive cells (76-100%) was greater for Bloom's grade I (1/29: 34%) than for grade III (10/66: 15%). A significant correlation was found between the percentage of immunoreactive cells and the cytosolic concentration of progesterone receptors. The morphological intracellular identification of GCDFP (due to its greater sensitivity) and its correlation with progesterone receptors allowed a more precise evaluation of the functional state and the hormonal dependency of the breast cells by underlining the heterogeneity of the tumoral cell population.
The ultrastructure of 47 primary breast cancers was studied. For each tumour, the characteristics of approximately 200 malignant cells were examined. Eleven features were scored from 1 to 3 and multivariate analysis showed that seven of these could be used to define an ultrastructural index of differentiation. Differentiation at the ultrastructural level was associated with the presence of steroid receptors. Differentiated tumoral cells contained oestrogen receptor and progesterone receptor in 81.8% and 66.7% of cases, respectively. Poorly differentiated cells contained oestrogen receptors in 50% and progesterone receptor in 14.3% of cases. Comparison of histological grading by the method described by Scarff, Bloom & Richardson with the ultrastructural index of differentiation showed a rather loose correlation which was not significant in this group of 47 patients. The authors conclude that differentiation at tissue or cellular levels yields differing information, only the latter being closely correlated with steroid receptor presence.
Alphalactalbumin was investigated in breast cells using the immunoperoxidase technique with a specific anti-alphalactalbumin serum. In 50 benign tumors alphalactalbumin immunoreactivity was demonstrated in the epithelium of fibroadenomas and in fibrocystic disease showing apocrine metaplasia. Alphalactalbumin immunoreactivity, investigated in 124 breast cancers, was present in all cells of lobular tumors but in only 76% of other cancers where the pattern was heterogeneous. Perineoplastic mammary tissue of normal appearance was not labeled with the anti-alphalactalbumin antiserum except where lobular hyperplasia was present. The presence of alphalactalbumin-type immunoreactivity was not correlated with the histopathological staging of Bloom and Richardson, nor with menopausal status. The incidence of positivity was 90% when estrogen and progesterone receptors were present in the tumor. The demonstration of alphalactalbumin using immunoperoxidase could be used to complement the histological classification of breast cancers.
A radical panhysterectomy and bilateral pelvic lymphadenectomy was performed immediately after intracavitary radiation in 240 cases of carcinoma of the uterine cervix. In some cases external radiation was performed after surgery. The 10 years survival rate was: 76 per cent in 169 stage I, 57 per cent in 71 stage II. Twenty seven patients died from recurrence or metastasis. Iatrogenic urinary tract complications were responsible of the death in 12 cases. All these cases were submitted to external radiation.
Between 1963 and 1971, a total of 406 inoperable cases of cervical cancer were treated by high-dose radiotherapy at the Centre René-Huguenin. Most of the patients (243) were irradiated by continuous therapy. In the other group (163) there was a 3-week interval in the middle of the treatment. The five-year survival rates (direct method) were respectively 60 and 39 per cent for the patients staged as T2 and T3. Local cure rates were 85 per cent for T2 and 65 per cent for T3. Unfortunately a high rate of complications was noted (12%), 4 per cent of which were fatal. Classical radiotherapy proved to be more beneficial than "split-course" technique considering survival rates. Yet, the rate of local cure is identical in both procedures, and the large rate of death in "split-course" seems to be irrespective of the method. Nevertheless, we have abandoned the "split-course" because the incidence of sequelae had not improved and in as much as the total dose had been reduced, the continuation of such therapy was less justified.
More than 1200 patients per year are treated in the Radiation therapy department of the ‘Centre René Huguenin'.A harmonious distribution of patients between therapists must ensure some freedom in the choice patient-therapist, balance the work load of each therapist and take into account the specialization of each one.A systems approach has led us to design a two-level structure: a distribution pattern is set up at management level on an annual basis; every week, actual results are taken into account; the next patients are simulated and the receptionist is given a command that aims at the decided distribution.Three years of operation enable a concrete evaluation of the working characteristics: permanent knowledge of the distribution, flexibility, lightness of the computerized part and psychological impact.Le service de radiotherapie du Centre René Huguenin traite plus de 1200 malades par an.La répartition harmonieuse de cette clientèle entre les six radiothérapeutes doit assurer une certaine liberte dans le choix malade–médecin, équilibrer la charge individuelle de chaque radiothérapeute en respectant leur spécialisation par localisation anatomique.La méthodologie de la dynamique des systèmes a conduit à établir une structure à deux niveaux: discussion annuelle de la répartition visée, consigne hebdomadaire programmée, donnée à l'htesse chargée des rendez-vous.La partie programmée fournit le plan d'affectation des malades à venir en fonction des résultats pondérés des semaines anterieures, des affectations déjà connues, de la disponibilité des médecins et de la répartition visée. La méthode d'affectation cherche à minimiser l'écart entre la répartition visée et la répartition prévue.Trois ans de fonctionnement permettent d'évaluer concretement les caracteristiques opérationnelles du système: connaissance précise de l'évolution de la répartition, rattrappage souple des écarts, légèreté du processus informatique et impact psychologique.