Clinical and biological characteristics of breast cancers in post-menopausal women receiving hormone replacement therapy for menopause.

The paradox of an excess breast cancer incidence among current users of hormone replacement therapy (HRT) without excess in breast cancer mortality raises the question of possible differences in the clinical and biological characteristics of cancers in current HRT users compared to non-users. A consecutive series of 129 post-menopausal patients under HRT for at least 6 months, in whom an operable breast cancer was diagnosed from January 1992 to December 1996, were identified retrospectively. In most cases women had received combination HRT (estrogen and progestative) and the mean duration was 60.4 (range: 6-360) months. Breast cancers diagnosed in post-menopausal patients during 1992-1993 at the Institut Curie constituted the reference series. Cancers in patients receiving HRT were smaller: 78% versus 32% T1 and 12 mm in larger diameter versus 29.5 mm. They were also more often diagnosed radiologically (49 versus 33%). A second group of 420 post-menopausal breast cancer patients whose samples had been referred for steroid hormone receptor and flow cytometric analysis in 1992-1996 were used for comparing biological and pathological information. Cancers of patients receiving HRT tended to be more often grade I and rarely grade III in the Scarf Bloom Richardson classification. Percentage of cells in S-phase as measured by flow cytometry was considerably lower in HRT users compared to control (mean 2.4 versus 3.7, median 2.2 versus 2. 6). Lymph node invasion, ploidy, and steroid hormone receptor expression did not differ significantly between the 2 groups. This apparently more favourable phenotype of breast cancers diagnosed in post-menopausal patients receiving HRT compared to unselected non-HRT users was not confirmed when analysis was restricted to breast cancers of less than 25 mm in diameter. If, as expected, the phenotypic information bears out in terms of prognosis, this may contribute to overcome the reticence in prescribing HRT due to the increased risk of breast cancer. However, it is still not clear whether the biologically less aggressive phenotype is related to the hormone treatment or is simply due to early detection.

The p53-positive phenotype of breast cancers.

One hundred and eighty-one breast cancer specimens were analyzed for nuclear p53 staining by immunochemical methods. There were 123 fine-needle cytological specimens and 58 frozen tissue sections of surgical biopsies. The microscopic evaluation of the staining fitted with a 4 group classification. Ninety-one samples (50.6%) were devoid of any staining (-), while 42 (23.3%) showed only few stained nuclei (+/-), typically around 1%. Thirty-two (17.8%) samples presented with strong nuclear staining (++) which in practically all cases concerned more than 50% of the nuclei, but a few cases showed staining heterogeneity. A further 17 cases (9.4%) presented with nuclear staining which concerned 10-20% of the cancer cells (+). This four class system was used to compare p53 expression with other prognostic parameters. A strong inverse correlation was observed with steroid hormone receptor content and p53 positivity was highly significantly associated with higher S-phase. All but one of the highly positive cases were aneuploid. Twenty-five percent (29/120) of the aneuploid tumors were strongly stained and a further 10% were considered positive (+). On the other hand, only 5 out of 59 DNA-diploid tumors were considered as + and one ++. The DNA index distribution according to p53 positivity showed peaks of positivity for hypodiploid, triploid and hypertetraploid values. Negative tumors were in all regards similar to those with only few stained nuclei, in particular mean S-phases of 2.8 and 3.3% respectively. Altogether, the typical strong p53 phenotype concerned a DNA-aneuploid tumor with above median S-phase fraction (mean of 7.1%), negative steroid hormone receptors and cytoprognostic index III. The p53 positive cases (+), were frequently steroid hormone receptor positive and had on the average intermediate S-phase fractions (4.3%). The proportion of immunochemical positivity (27% in our series), is compatible with the published frequency of p53 mutations detected in breast cancers, but the differences in the phenotype according to the level of positivity should be further investigated.

Frequently elevated content of immunochemically defined wild-type p53 protein in colorectal adenomas.

Mutations of the p53 tumour-suppressor gene are considered to be rare in human colorectal adenomas, a premalignant state of the digestive tract. We have analysed a series of 32 exophytic tumours of the colon and rectum for the presence of p53 protein. In 26 of the 28 pure adenomas, the presence of significant levels of p53 proteins was established by a sensitive two-point enzyme-linked immunosorbent assay. The detectability of p53 protein was frequently limited to PAb 1801, recognizing an N-terminal epitope. Immunoblotting of the fractions captured by the monoclonal antibodies revealed that PAb 421 reacted exclusively with a 53-kDa species, whereas an additional 48-kDa band was detected after incubation with PAb 1801. In the adenomas, the mutant conformation-specific PAb 240 was always negative and no mutations were detected on exons 5-8 in three large and highly dysplastic lesions, selected for their high p53 protein content. The remaining four of the 32 tumours presented foci of cancer. Three of these were shown to contain 'mutant' PAb 240-reactive p53, and gene mutations were identified in two by denaturing gradient gel electrophoresis and sequencing of the amplified products. Intense p53 nuclear immunohistochemical staining was associated with the malignant areas. We conclude that a novel mechanism affecting the regulation of p53 protein could occur in colorectal adenomas.

In-vivo transperitoneal fertilization.

We present the technique of in-vivo transperitoneal fertilization (IVTPF) as a first approach to infertility treatment in couples with male subfertility or unexplained factors. The technique is statistically less successful but also less invasive than either gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization - embryo transfer (IVFET) and offers considerable advantages over intrauterine insemination (IUI). The IVTPF technique involves transperitoneal transfer of processed spermatozoa within the pouch of Douglas after induction of ovulation. We report our 4-year experience with IVTPF which includes 136 treatment cycles in 89 couples. Eight pregnancies were achieved in 89 patients (9%) and 136 treatment cycles (7%). Fifty-one patients (57%) received IVTPF for only one treatment cycle; seven of the eight IVTPF pregnancies occurred in this group. An ectopic pregnancy resulted in one of the eight IVTPF pregnancies (13%). The functional quality of the sperm in those couples who achieved pregnancy was statistically superior to those couples who did not conceive. However, pregnancy was also obtained in case of severe oligozoospermia. Based on our experience, we feel IVTPF to be a very reasonable first approach in patients with no pelvic pathology and with infertility secondary to male factors or unexplained causes.

[Benign cysts of the ovary. Homogeneous experience in 22 cases observed in 10 years]. / Kystes bénins de l'ovaire. Expérience homogène de 22 cas recueillis en 10 ans.

The authors present their experience with benign ovarian cysts based upon a series of 22 cases. Occurrence age displayed 2 peaks neonatal and para-pubertal. Ultrasound and coelioscopic examination would help in the management of such functional cysts where spontaneous regression must be weighted with potential complications.

[Papilloma viruses: group-specific antigens within lesions of the oral mucosa]. / Virus papilloma: antigènes spécifiques de groupe au sein de lésions des muqueuses buccales.

The present study was undertaken with purpose to investigate the relationships between intraepithelial proliferations of malpighian mucosa and the presence of group specific papilloma virus antigens. The investigations allowing to give viral types or subtypes, the hybridization technics, are very heavy and not disponible in routine practice. The detection of widely distributed genus specific HPV antigen using PAP immunohistochemical labeling in different lesions and their association with displastic or neoplastic processes is presented. Only few studies were performed on oral mucosal proliferations, showing the association of these viral proteins with papillomatous or condylomatous lesions. Our work is directed towards the identification of the HPV antigens in more advanced lesions and in the mucosal epithelium surrounding and perhaps preexistent with the buccal cancer.

[Salpingitis in children before puberty. Apropos of 2 cases]. / Salpingite de l'enfant avant la puberté. A propos de deux cas.

Salpingitis is exceptional in pre-pubertal girls. The authors compare a case of histologically and bacteriologically well documented salpingitis in a 3 year old girl to another case in a pre-pubertal 14 year old girl and review the literature on the subject. Six other cases have been reported. The clinical presentation is very variable and, in the absence of ultrasonography or laparoscopy, laparotomy is required for both the diagnosis and the treatment.

[Presence of papilloma group viral antigen in an esophageal condyloma in man]. / Présence d'un antigène viral de groupe "Papilloma" dans un condylome oesophagien chez l'homme.

A case of esophageal Papilloma is reported. The viral condyloma was diagnosed by standard histological methods and confirmed by immuno-fluorescence and immuno-peroxidase technics against genus specific Papilloma virus antigens (i. e. capsid specific proteic antigen). These antigens were localized in the nuclei of koilocytic cells. These results confirm the association between proliferative lesions appearing on the mucosal epithelium and Papilloma viruses, which are suspected to be oncogenic in other malpighian tissues.

[Familial lymphohistiocytosis. Anatomopathological study of 2 cases detected neonatally]. / Lymphohistiocytose familiale. Etude anatomopathologique de 2 observations à révélation néonatale.

Two brothers presented with hemophagocytic reticulosis with neonatal onset. Early clinical and biological symptoms included pallor, hepatosplenomegaly and anemia, thrombocytopenia. Evolution was lethal in both cases, at 5 months and 13 days of age, respectively. Diagnosis was confirmed in both by the pathologic findings: diffuse lymphohistiocytic cellular proliferation with hemophagocytosis and atrophy of the lymphoid tissue. The diagnostic difficulties of this disease in the neonatal period are emphasized.

[Thyroid involvement in histiocytosis X]. / Localisation thyroïdienne d'une histiocytose X.

A thyroid involvement is reported in a 10 year-old boy with histiocytosis X. It was revealed by goiter and hypothyroidism following diabetes insipidus and growth hormone deficiency. Hypothyroidism was exclusively due to the invasion of thyroid by the tumor, while the other endocrine changes were in favor of the histiocytic infiltration of hypothalamus. The exceptional feature of thyroid involvement in disseminated histiocytosis X is emphasized.

An original hypercalcemic infantile renal tum or without bone metastasis: heterotransplantation to nude mice: report of two cases.

Two cases of hypercalcemic infantile renal tumor without macroscopic bone metastases are reported. Optical and ultrastructural characteristics as well as biological and clinical data are sufficiently different from those of other infantile renal tumors to justify the individualization of an original tumor entity. The hypercalcemia is not clearly understood but may be related, in one case, with a high N terminal PTH serum level. Ultrastructural elements (secretory granules) and polypeptide hormone products (glucagon) are discussed in relation with APUD cells characteristics.

[Association, in the same subject, of deletion of the short arm of chromosome 4 (4p-) and of complete deficiency of parahydroxyphenyl-pyruvate oxidase activity in the liver (tyrosinosis)]. / Association, chez le même sujet, d'une deletion du bras court du chromosome 4 (4p-) et d'un deficit complet en parahydroxyphenylpyruvate oxydase hépatique (tyrosinose).

The authors report the association in a child of monosomy 4p- and tyrosinosis. They discuss the localization of the para-hydroxyphenylpyruvate oxidase locus on the short arm of chromosome 4. They suggest the study of para-hydroxyphenylpyruvate oxidase activity in each child with monosomy 4p-.

[Johanson-Blizzard's syndrome: another cause of pancreatic lipomatosis (author's transl)]. / Le syndrome de Johanson-Blizzard. Une autre cause de lipomatose pancréatique.

A new case of Johanson-Blizzard's syndrome is reported. It concerns a boy born to consanguineous parents and who died at the age of 10 months from malnutrition. Anal imperforation, alar agenesia, hair anomalies, mental retardation and external pancreatic failure were associated. Neither deafness nor hypothyroidism appeared to be present. Autopsy revealed lipomatous hypoplasia of the exocrine pancreas, hitherto unobserved in this syndrome, and probably responsible for the external pancreatic failure noted in published cases. The variability within a given family of the Johanson-Blizzard malformative syndrome is illustrated by two other cases reported in the anamnesis, one involving a brother who had died earlier with cutaneous aplasia at the fontanella and lacrimal canal malposition and one involving a second cousin who presented with isolated anal imperforation.

[Granular cell myoblastoma or Abrikosov's tumor of the esophagus]. / Tumeur à cellules granuleuses, dite tumeur d'Abrikossoff, de l'oesophage.

Granular cell myoblastoma or Abrikossoff's tumor of the esophagus are exceptional: fiveteen cases have been described in the literature. In this work we present the following case: discovery of a sub mucosal tumor during a systematic fibroscopic examination of an anemix patient. Only histological examination was able to make the diagnosis.

Multifocal myocardial necrosis and fibrosis in pancreatic diseases of children.

From a review of 2,000 autopsies of children, 16 cases of extensive necrosis and scarring fibrosis of the myocardium were found. These lesions involved mainly the left ventricle and spared the endocardium, the pericardium, and the coronary vessels. These necrotic of fibrotic heart lesions were found to be closely associated with various pancreatic diseases: cystic fibrosis (11 cases), pancreatic lipomatosis (2 cases), extensive small bowel resection (3 cases, 2 of which were associated with acute interstitial pancreatitis). To explain these unexpected associations, two hypotheses can be put forth: (1) The lack of absorption of some presently undetermined substances indispensable for the correct trophicity of the myocardium, and (2) the release in the blood of proteolytic enzymes with consecutive activation of phlogistic substances such as kinins.

[Intrahepatic organic cystals in artificial feeding of children (author's transl)]. / Cristaux organiques intrahépatiques au cours des nutritions artificielles chez l'enfant.

Crystals have been observed in the liver of 4 children, submitted to a parenteral nutrition and or, continuous enteral nutrition. Those crystals appear to be birefringent with polarized light extra and intracellular in electron microscopy, they contain a large amount of calcium, phosphore and sulfur. They are thought to represent organic crystals precipitating within the bile ductules of the portal areas. The occurence of those organic crystals seems to be related to a lack of bile secretion due to the exclusion of kinetic and secretory activity of the stomach and the duodenum.

[Choleriform diarrhea in a case of ganglioneuroblastoma. Demonstration of a high blood level of vasoactive intestinal peptide (VIP)]. / Diarrhée chlorériforme dans un cas de ganglioneuroblastome. Mise en evidence d'un taux plasmatique élevé de "vasoactive intestinal peptide" (V.I.P.).

The case of a 6-month old infant presenting with profuse diarrhea associated with increased plasma V.I.P. (600 pg/ml) is reported. The increased excretion of V.I.P., most probably of tumoral origin may be considered as responsible for the diarrhea. The discovery of an increased plasma level of V.I.P., occuring during a choleriform diarrhea, leads to evoke and search for a tumoral process of the APUD system.