H19 overexpression in breast adenocarcinoma stromal cells is associated with tumor values and steroid receptor status but independent of p53 and Ki-67 expression.

In a previous study we described the expression of the H19 gene by in situ hybridization (ISH) in normal breast and in benign or malignant breast tumors (Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D, Coll J: Biol Cell 1995, 85:117-124). In the present work, 1) we extend the previous one to a statistically useful number of adenocarcinomas, including 10 subclasses, 2) we provide information on the precise ISH localization of the H19 RNA by using, on serial tissue sections, antibodies delineating specifically the stromal or the epithelial component of the breast, and 3) we consider relationships between the H19 gene expression and various clinicopathological information as tumor values (T0 to T4), grades, steroid receptors, lymph node status, and molecular features as the p53 gene product and the Ki-67/MIB1 protein, which is specific to proliferating cells. Data indicate that 1) in 72.5% of studied breast adenocarcinomas an overall H19 gene expression is increased when compared with healthy tissues, 2) the H19 gene is generally overexpressed in stromal cells (92.2%) and rarely in epithelial cells (2.9% only), 3) an up-regulation of the H19 gene is significantly correlated with the tumor values and the presence of both estrogen and progesterone receptors, and 4) at the cellular level, the H19 gene demonstrates an independent expression versus accumulation of both the p53 protein and the Ki-67/MIB-1 cell-cycle marker.

[Malignant non-Hodgkins lymphoma manifested in an ovarian tumor. Five case reports]. / Lymphomes malins non hodgkiniens révélés par une tumeur ovarienne. A propos de 5 observations.

Five cases of non-Hodgkin malignant lymphoma (NHML) presenting as ovarian tumours are reported. All corresponded to disseminated lymphomatous disease, none was of low grade. Ultrasound showed a solid, most often homogeneous, hypoechoic, bilateral mass in 4 of 5 cases. Its association with many lymph nodes and mainly parenchymal localisation suggested of the NHML. Only histologic and immunohistochemical findings may provide the final diagnosis. The biopsy for those studies should be obtained as least invasively as possible because treatment of NHML is chemotherapy.

Epithelioid sarcoma of the tongue.

A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously.

The H19 gene is expressed within both epithelial and stromal components of human invasive adenocarcinomas.

In a previous work, we have isolated the human H19 gene and shown accumulation of transcripts in various human tumors including breast carcinomas (Douc-Rasy et al (1993) Int J Oncol 2, 753-758). Questions arose, after Northern blot results, about the precise H19 mRNA location, specially in normal breast tissues and benign or malign primary breast tumors. Then we performed molecular in situ hybridization to get insight into tissue expression of the H19 gene. Examined resections included one normal tissue, one fibroadenoma and 13 cancers. Results obtained with the H19 probe can be summarized as follows: 1) in normal breast tissues signals were focally observed in epithelial cells, but more predominantly in the palleal tissue which is sensitive to hormones; 2) in the fibroadenoma, fibroblastic cells were extensively labeled at the stroma-epithelium boundary, but epithelial cells were negative; and 3) in primary cancers, eight specimens exhibited signals on stromal cells, one specimen on epithelial cells and four on both epithelial and stromal cells. Data provide the following evidence: 1) usually labeled cells are clustered, either within normal or pathological tissues; 2) the labeling pattern highly differs from one tumor to another; and 3) H19 probe displays very different signals from one cell to another in given compartment of a given tissue section. In conclusion, it seems that a high H19 expression matches the tumor invasion. Our results suggest that the expression of this gene is concerned by the relationships between epithelial and stromal cells, and can reflect peculiar physiological states of the cells. Furthermore, we discuss results showing an abundant expression of H19 gene in some adenocarcinomas of bad prognosis, in the context of the otherwise established tumor-suppressor role of this gene, or the strictly controlled gene dosage, which could be overridden in these particular cases.

Type I insulin-like growth factor receptors in human colorectal cancer.

Type I insulin-like growth factor (IGF) receptors have been recently characterised in human colorectal cancers. The aim of this study was to determine whether type I IGF receptor concentration may be related to prognostic variables in colorectal cancers. Saturation experiments with [125I]IGF-I were performed on membrane preparations of 46 frozen specimens (20 tumours, 26 controls) and analysed according to the Scatchard method. In all the studied cases, we found a single class of high affinity binding sites in both normal and malignant colorectal tissues (median 0.17 and 0.15 nmol/l, respectively). Using paired analysis, we found no significant difference in terms of type I IGF receptor concentration between malignant and normal colorectal tissues. There was also no relationship between type I IGF receptors and any of the tumour characteristics studied. This study does not support a critical role of the type I IGF receptors in the clinical management of colorectal cancers.

Is there a role for cervicography in the detection of premalignant lesions of the cervix uteri?

The characteristics of cervicography and the Papanicolaou smear test have been compared for the detection of cervix lesions classified as CIN I or more. A total of 4,015 women were entered into the study. The sensitivity of cervicography is significantly higher (McNemar test, P < 0.0001), but its specificity remains significantly lower (McNemar test, P < 0.0001), and its higher sensitivity does not apply to lesions classified as CIN II or more (high-grade lesions). Hence, if patients with a positive screen result are to be referred for colposcopy-biopsy, cervicography is not a suitable alternative to the smear test for the screening of cervical cancer. However, cervicography can be envisaged as a complementary tool to the smear test because of (a) its higher capability to detect high-grade lesions among women less than 35 years old and (b) its potential superiority in following low-grade lesions. It may also serve as a tool for quality assurance audit of the smear test.

Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency.

Nine pathologists from different institutions reviewed in a double-blind study 16 breast tumors previously indexed as typical medullary carcinoma, atypical medullary carcinoma, or infiltrative ductal carcinoma. A set of 16 slides was circulated two times among the nine pathologists. The diagnoses of typical and atypical medullary carcinomas were based on a definition given by Ridolfi et al. The interobserver and intraobserver agreement was low, with a kappa value of less than .50. The only histological criterion that had more than 50% agreement was the presence or absence of an in situ component in the tumor, assuming that the disagreement of one pathologist is accepted. This study is a snapshot of the problems encountered in the diagnosis of typical medullary carcinoma in a routine context and it shows high levels of variations in diagnostic consistency.

Comparative study of intravenous and intraarterial cis-platinum on intratumoral platinum concentration in carcinoma of the cervix.

In order to define the influence of intraarterial administration of cis-platinum in tumors of the cervix, a preliminary crossover study was performed to measure and compare the intratumoral concentrations (ITC) of platinum obtained respectively after intravenous (iv) and intraarterial (ia) (both bilateral hypogastric arteries) injection. The results in nine patients demonstrate that higher (P = 0.05) intratumoral concentrations are obtained after intraarterial injection of cis-platinum: 10; 3.7-23.7 ng Pt/mg of dry tissue after ia (median; range) 6.9; 4.1-23.6 ng Pt/mg tissue after iv. This difference is probably too small to be of clinical significance and a comparative clinical trial does not seem to be warranted. The results also show a large intersubject variation in intratumoral platinum concentration which are reproducible in patients whatever route of administration is used. Thus the observed differences in ITC are more related to the variability of the tumor properties than to the route of administration.

Presence and characterization of insulin-like growth factor 1 receptors in human benign breast disease.

Insulin-like growth factor 1 binding sites were characterized in human benign breast disease. We demonstrated the presence of one high affinity binding site. Chemical cross-linking of [125I]IGF1 to benign breast disease membranes in reducing condition and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed one band with an apparent Mr of 130,000. The specificity of the binding was studied: IGF 2 was a good competitor whereas insulin competed for binding with a potency lower than 1/100 that of IGF1. This IGF1 binding corresponded to the previously described type I IGF receptor (IGF1-R). IGF1-R was assayed in 35 cases of benign breast disease and two samples of normal breast tissue. Forty-three per cent of the lesions were IGF1-R positive. The mean geometric level of specific binding was 1.98% in the whole population, it was significantly lower in adenofibromas (1.55%) than in epithelial hyperplasia (2.5%); it was 2% in dystrophic disease. IGF1-R was undetectable in normal tissue. Considering our previous results showing that almost all the breast cancers contained IGF1-R, these data suggest that the increase in IGF1-R could be a marker of malignant tumor development.

[Cancer of the ovary. Comparative value of serum CA-125, immunochemistry and biological tests of inflammation]. / Cancer de l'ovaire. Intérêt comparé du Ca-125 sérique de l'immunohistochimie et des tests biologiques de l'inflammation.

The marker CA-125 is not specific of malignant ovarian tumors but, when its titration is positive, its evolution permits to follow correctly the development of the tumor. The authors report their experience with 180 titrations coupled with the titration of inflammation markers.

Stimulation of DNA synthesis by prolactin in human breast tumor explants. Relation to prolactin receptors.

Breast-cancer tissue from 38 patients was tested for prolactin sensitivity by measuring both 16-hour (3H)dT incorporation in tissue fragments during 24-hour organ cultures, and prolactin receptors in tumor specimens. We observed a stimulation of DNA synthesis by prolactin in 6/38 (16%) cases; the stimulation was maximum with physiological concentrations of prolactin (0.05 to 0.2 microgram/ml medium). The stimulation of DNA synthesis never occurred in the absence of prolactin receptors. There is no relation between the response to prolactin and estradiol or progesterone receptor levels, but in four cases the stimulation was observed when the three receptors were present. Finally, the response to the stimulation was independent of the clinical stage of the patient.

[Nasopharyngeal epitheliomas: experience of the Regional Cancer Control Center in Lille (79 cases 1970-1982)]. / Les épitheliomas nasopharyngés: expérience du Centre Régional de Lutte contre le Cancer de Lille (79 cas de 1970 à 1982).

From 1970 to 1982, 79 cases of nasopharyngeal carcinomas were treated at the Regional Cancer Center of Lille (France). At the term of the study, it appears that patients of Central Europe origin have a rather high risk of NPC (17% of cases, that ethnic population representing about 8% of all superior aerodigestive tract carcinomas). The classical differences between well and undifferentiated tumors are founded, the first presenting local spread the other general involvement.

[Sarcoma of the uterine body]. / Sarcomes du corps utérin.

This work is a retrospective study of the sarcomas of the uterus which were treated at the Oscar Lambret centre in the last ten years. The difficulty in diagnosing sarcomas of the uterus by the histologist can be appreciated when it is realised that classification of uterine sarcoma is complex. It is not possible to give any statistical interpretation of what is found because of the relative rarity of the cases (about 3% of all cancers of the body of the uterus). The clinical, radiological and histological aspects have been studied. Prognosis is very bad. This means that the type of pathological anatomy that has been found determines the treatment.