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Biomedical subjects

L Piana

Publications and source records attributed to L Piana.

At least 19 recordsLinked to original sources

[Modalities of reading of detection mammographies of the programme in the Bouches-du-Rhône. Results and costs 1990-1995].

In the Bouches du Rhône breast cancer screening programme, mammograms are read by two separate radiologists of different levels of training. All women with at least one positive reading are recalled for further assessment. During the first round, 3,477 of the 95,967 screenees were recalled by the first reader and 2,321 by the expert reader. The expert increased cancer detection by 15% and 45% of cancers detected by the expert were smaller than 11 mm. The marginal cost of double reading was 21,838 Francs per additional cancer detected. Double reading thus allowed for the detection of cancers of good prognosis which would have gone undetected by a single reader. Its cost seems justified by its impact on the effectiveness of the screening programme.

Aged

[Lymphocytic mastitis].

Lymphocytic mastitis is a non infectious inflammatory disease of the breast with lobulocentric lymphocytic infiltrate of variable intensity, collagenous fibrosis and progressive lobular atrophy. The pathogenesis of lymphocytic mastitis is still unknown but some recent reports have suggested an autoimmune origin. We investigated a series of 10 cases by immunohistochemistry and we collected patients' biologic data. The most striking histologic feature was a prominent lobulocentric stromal or intraepithelial lymphocytic infiltrate. Occasionally, the infiltrate was perivascular and nodular along the lobule border. B and T lymphocytes, both demonstrated by immunophenotypic analysis, were shown with a particular pattern of distribution. Pathologists must be aware of this disease in order to recommend immunological investigation.

Adult

Quantitative immunocytochemical assays on frozen sections of p53: correlation to the follow-up of patients with breast carcinomas.

A series of 222 tumor samples stored at -80 degrees C in the authors' tumor library were investigated with anti-p53 (PA 1801) and streptavidin-biotin-peroxidase complex. The p53 immunoprecipitates were quantified by densitometry assessed by image analysis of digitized microscopic images. Two parameters, percentage of positive surface and mean optical densities, were compared with the patient's outcome (follow-up = 96.8 months) (life table method, Mantel Cox test, BMDP statistical software). The p53 expression significantly correlated with a poor overall survival (P = .0063), metastasis-free survival (P = .024), and recurrence-free survival (P = .022) at a 20% cutoff point of positive immunoreactive tumor surface. A strong prognostic significance was observed in the node-positive subset of patients but not in the node-negative subset, except for recurrence-free survival (P = .047). The results indicate the clinical relevance p53 evaluated by quantitative immunocytochemistry.

Adult

Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition?

Some controversy remains about the clinical or pathological definition of the different types of inflammatory breast cancer (IBC) and especially the diagnostic and prognostic value of dermal lymphatic involvement. Our purpose was to classify the different types of IBC for which diagnosis was confirmed intraoperatively and ascertain features allowing reliable diagnosis. We studied clinical findings, biological data, and treatment outcome in a series of 144 successive patients. Our results suggest that there are 2 biologically different entities i.e., true IBC and pseudo-IBC. True IBC, whose course is currently fatal in all cases, can be divided into 2 sub-categories i.e., common true IBC (75.7% of cases), in which inflammatory signs occur primarily or secondarily, and occult true IBC (13.2% of cases). Dermal emboli have been observed in 61% of common true IBC, but their absence did not alter the rapidly unfavourable outcome. Extensive lymph-node involvement, other biological features and survival were the same in the 2 sub-categories. Pseudo-IBC (11.1% of cases) can easily be confused with common true IBC. The biological characteristics of pseudo-IBC differ from those of true IBC: no dermal lymphatic involvement and little or no lymph-node involvement. Despite large tumour size, outcome was particularly favourable. It is of great importance to differentiate true and pseudo-IBC, for which the treatments are different. Confirmation of true IBC requires pathological demonstration of dermal lymphatic emboli or extensive lymph-node involvement. Occult IBC must be identified for patients presenting rapidly growing tumours.

Adenocarcinoma

Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features.

The relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow-up: 62 months). Three groups were compared: patients under 35 years of age, non-menopausal patients over 35 years of age, and post-menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis-free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph-node involvement and receptor status. Multivariate analysis of both overall and metastasis-free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence.

Adult

Clinical and biologic prognostic factors in breast cancer diagnosed during postmenopausal hormone replacement therapy.

OBJECTIVE: To ascertain the influence of hormone replacement therapy on clinical and biologic prognostic factors of breast cancer. METHODS: Between 1976-1992, we treated 1081 postmenopausal women for breast cancer at our institution. Of these, 68 were undergoing postmenopausal hormone replacement therapy at the time of diagnosis. These patients were compared with a matched control group of 272 breast cancer patients who had not undergone prior hormone replacement therapy. RESULTS: Patients who developed breast cancer during hormone replacement therapy had fewer locally advanced cancers (large tumors and extensive lymph node involvement) and more well-differentiated cancers (infiltrating lobular cancers and grade 1 cancer). The number of patients with estradiol or progesterone receptors was lower in the hormone-treated group. Metastasis-free survival curves showed a tendency (P = .05) for better prognosis in hormone-treated patients both overall and in stage T2. CONCLUSIONS: Hormone replacement therapy per se does not affect the prognosis of breast cancer. Regular surveillance during hormone replacement therapy reduces the number of locally advanced cancers and thus improves the survival rate. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones.

Adult

p53 quantitative immunocytochemical analysis in breast carcinomas.

A series of 200 breast carcinomas was investigated on frozen sections using PAb 1801 p53 monoclonal antibody and streptavidin biotin peroxidase complex. Densitometric analysis of the immunoprecipitates was assessed by processing digitized microscopic images. p53 was observed in the nucleus of 48% of the tumors. Some tumors (14 of 91) tested in parallel on paraffin sections were negative, although positive on frozen sections. Image analysis showed that the surfaces positive with anti-p53 and the staining intensity were decreased (P < .01) on paraffin sections. The p53 tumor expression was independent of patient age, tumor size, axillary lymph node status, HER-2/neu and cathepsin D expression, and nuclear morphometric parameters. However, p53 correlated with high histological grade (P < .01), lack of estrogen receptor (ER) (P = .0015) and progesterone (PR) (P = .0065) antigenic sites, pS2 detection (P = .03), high Ki-67 immunoreactivity (P = .018), large silver-stained nucleolar organizer region (AgNOR) nuclear surface ratio (P < .02), and degree of hyperploidy (P < .03), and was more often observed in the comedocarcinomas. The results suggest that p53 expression in breast carcinomas is not a totally independent prognostic indicator and that the clinical relevance and prognostic significance of p53 expression in breast carcinomas can be reliably assessed provided that the procedures are standardized, particularly with regard to the use of frozen sections and image analysis processing of the immunodetection.

Adult

Reproductive factors and breast cancer risk. Effect of age at diagnosis.

The data from a French case-control study of 495 patients with breast cancer and 542 control subjects interviewed in five French public hospitals, were analyzed to assess the effect of reproductive factors (age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity) on the risk of breast cancer. Age at menarche, age at first full-term pregnancy, the time interval between these two ages, and parity appeared to have a limited influence on breast cancer risk. However, the relationship between these factors and the risk of breast cancer varied according to the age at breast cancer diagnosis. In the youngest group of women, the most consistent effects came from factors occurring early in life (menarche, first full-term pregnancy, and consequently the time interval between these two events). These factors had a null or weak effect on the oldest group of women. The protective effect of high parity was confined to the oldest group of women.

Adult

CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors.

The distribution of PECAM-1/CD31 molecule was investigated in 133 breast carcinomas using monoclonal antibody and frozen sections. Anti-CD31 labels endothelial cells and reflects stromal angiogenesis. The CD31 immunoreactivity was evaluated by computer-assisted analysis of digitized microscopic images. The automatic screening of the whole preparation and the measurements of the mean CD31 immunostained surface was performed in each case. A similar procedure was achieved for p53, cathepsin D, P-gp, pHER-2/neu, Ki67, pS2 estrogen and progesterone antigenic sites immunodetection. The image analysis of positive CD31 surface was variable, ranging from 4% to 33% (mean 14.7%, SD = 5.43). The CD31 positive surface correlated (P < .01) with the Nottingham prognostic index, but not with the tumor size, the node status, the tumor grade, nor with the patient age. Also the CD31 immunoreactivity was independent of the pHER-2/neu, Ki67 antigen, p53, ER, PR and pS2 immunodetectable expression in tumors, but correlates with that of cathepsin D (P = .024) and P-gp (P = .028), which reflects the multi-drug resistance capacity of tumor cells. In conclusion, CD31 positive vessels assessed on frozen sections by image analysis constitute an excellent method of evaluating tumor stromal angiogenesis, and can be further used for clinical purposes. The results also suggest that the CD31/PECAM molecule may be involved in the spread of tumor by interacting with extracellular matrix lysis that results from the tumor cell proteasic activity and with multidrug resistance.

Adult

Digitization of microcalcifications in breast radiographs. Correlation with pathologic data.

A series of 104 nonpalpable breast lesions detected by mammograms and containing microcalcifications were studied. Intraoperative radiographs of intact and sliced specimens were assessed, followed by microscopic diagnosis on frozen sections of areas containing microcalcifications. Microcalcifications detected on mammograms and radiographs of the specimens were digitized and evaluated in accordance with morphometric parameters, including the mean surface, shape factor, bend energy, envelope surface and total surface, total number and concentration of microcalcifications. Benign disorders, atypical hyperplasia and carcinomas accounted for 47.2%, 4.8% and 48% of the tissue lesions, respectively, but the disorders were most often heterogeneous and mixed. Most, but not all, parameters significantly correlated with the three types of radiographs, although radiographs of the sliced specimens provided images of the best quality. Only two parameters, mean size and bend energy, were significantly different (P = .008, .0036) in benign and malignant lesions. It is concluded that image analysis of digitized microcalcifications in radiographs may provide quantitative data helpful in mammogram interpretation.

Breast Neoplasms

Quantitative immunocytochemical assays of P-glycoprotein in breast carcinomas: correlation to messenger RNA expression and to immunohistochemical prognostic indicators.

BACKGROUND: Chemotherapy failure that is due to cellular drug resistance remains a major problem in most cancer patients. One type of drug resistance that has been characterized is the multidrug resistance phenomenon, which demonstrates a reduced ability of cancer cells to accumulate drugs as a result of the effects of an energy-dependent unidirectional drug efflux pump with a broad substrate specificity. This drug pump is composed of a 170-kd transmembrane glycoprotein referred to as the P-glycoprotein (P-gp) that uses energy in the form of adenosine triphosphate to transport drugs through a channel formed by transmembrane segments. PURPOSE: Our purpose was to detect the levels of P-gp expression in frozen untreated breast carcinomas by immunocytochemical assays and to correlate these levels to current prognostic indicators and, in a few cases, to MDR1 (also known as PGY1) mRNA expression by polymerase chain reaction (PCR). METHODS: The immunocytochemical expression of the multidrug resistance gene, P-gp, was investigated using a specific monoclonal antibody (JSB1) against P-gp in 5-microns frozen sequential sections of breast carcinomas obtained from 213 patients. Microscopic images of immunostained preparations were evaluated by image analysis and were compared with MDR1 transcription (mRNA) assessed by PCR in 16 patients. Quantitative P-gp immunocytochemical assays were correlated to histoprognostic factors and immunocytochemical indicators. RESULTS: Among the 213 breast carcinomas tested, 113 (53%) were P-gp positive, but in 28% of the tumors, the immunostained surface accounted for less than 5% of the total area stained. Quantitative immunocytochemistry reflecting the amount of intracellular P-gp antigen strongly correlated (r = 0.865; two-sided, P < .0001; Pearson's test) with the quantitative evaluation of the scanner analysis of mRNA transcripts. The P-gp expression was significantly (two-sided, P < .001) correlated with p53 expression in tumors, to cathepsin D and Ki67 (two-sided, P < .01) immunoreactivity, and to a lesser extent, the detection of estrogen receptor antigenic sites (two-sided, P = .019). P-gp expression was found to be independent of expression of progesterone receptor and pS2, pHER-2/neu, and CD31 in tumors and from patient age, tumor size, histologic types, grades and Nottingham prognostic index, and nodal status. CONCLUSIONS: The quantitative immunocytochemical assays of P-gp are correlated to PCR analysis of MDR1 expression, and such correlations can be useful in evaluating potential multidrug resistance in breast cancer. However, the clinical significance of P-gp immunodetections remains to be further determined.

ATP Binding Cassette Transporter, Subfamily B, Mem

Reappraisal of breast hamartomas. A morphological study of 41 cases.

Mammary hamartomas are breast disorders currently underestimated and not well recognized. Forty-one hamartomas diagnosed among 5,834 breast biopsies, histologically examined during the last 7 years, are reported. Hamartomas accounted for 1.2% of benign lesions and 4.8% of benign breast tumors. Clinically, hamartomas were revealed by breast palpable lump, usually painless. Typically, but inconsistently, mammography showed sharply circumscribed density, separated from adjacent normal breast by a thin radiolucent zone. Macroscopically, hamartomas were slightly larger and softer than common adenofibromas, were well limited, whitish, pinkish and fleshy, with yellow islands of fat tissue. Histologically, hamartomas exhibited pushing borders with a pseudoencapsulation, and consisted of a combination of variable amount of stromal and epithelial components. Stromal components mainly consisted in a prominent fibrohyalin feature usually associated to small islands of adipose tissue and edematous changes. Epithelial structures showed variable features of benign breast disease. The overall architecture was lobulated but not nodular. The histological diagnosis was mainly a diagnosis of exclusion and hamartomas diagnosis relies on clinical, radiological and pathological criteria. Hamartomas result more from breast dysgenesis than from tumorous process.

Adolescent

Prognostic significance of autoantibodies to laminin in the sera of breast cancer patients: a preliminary report.

Interactions between cancer cells and laminin play an important role in the metastatic cascade. The aim of this retrospective study was to evaluate the presence and the prognostic significance of autoantibodies to laminin in sera of patients with breast cancer. Our study population consisted of 71 high-risk primary breast cancer patients (median follow-up, 6 years). IgG, IgA and IgM were analysed at the time of surgery and before any treatment was given. Concentrations were measured by enzyme immunoassay with a highly purified antigen. IgG, IgA and IgM anti-laminin median values were, respectively 117%, 130% and 97% of normal absorbance. Higher concentrations of IgM to laminin were found in pre-menopausal patients as compared with post-menopausal patients (p < 0.001). Patients with high concentrations of IgG to laminin had lower disease-free (p = 0.003) and overall survival rates (p = 0.003). In breast cancer, assay of IgG to laminin could thus provide a cheap and easy prognostic index available for all patients.

Adult

[Impalpable cancers of the breast. Histological and immunohistochemical study].

Breast cancer screening enables the diagnosis of impalpable lesions detectable by mammography or ultrasonography. The diagnosis of impalpable cancers lacking macroscopic disorders is difficult. However the diagnosis is facilitated by X-raying of surgical specimens, which shows that screened breast lesions have effectively been excised and which exactly localize these lesions. In addition, the X-raying of sliced (5 mm thick) fresh surgical specimens during surgery, enables the intraoperative diagnosis on frozen section of 72% of breast carcinomas and a one step surgical treatment (clear specimen edges, axillary lymph node excision). Moreover, the intraoperative examination of surgical specimens enables appropriate sampling of tissue for delayed immunodetections on frozen sections. These immunodetections provide prognostic information complementary to current microscopic investigation, particularly relevant in small node negative tumors.

Breast Diseases

Familial risk of breast cancer in a French case-control study.

The relationship between a family history of cancer and the risk of breast cancer was investigated in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in families. This relationship increased linearly with both the number of the affected relatives and with the degree of kinship between the affected relative and the case. The highest risk was observed when a sister was affected by breast cancer. This could be explained by longer common environmental exposures between sisters than between mother and daughter. This could also be explained by a genetic factor segregating under a recessive model. The risk of breast cancer associated with colon, uterus, ovary, and prostate cancer in the family was not significantly different from one. However, the estimated odds ratios associated with a family history of colon cancer increased with the degree of kinship between the affected relative and the case in a similar manner to those of breast cancer. A relationship between the risk of breast cancer and a family history of colon cancer would support the existence of a common familial factor (be it genetic or not) for these cancers. Further genetic epidemiological studies might help to define the mode of inheritance of the same susceptibility to cancer at different sites.

Adult

Familial risk of breast cancer and abortion.

We found that the risk of breast cancer associated with a family history of breast cancer increased with the number of abortions (induced as well as spontaneous) in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. For the women who had undergone at least two abortions, the risk associated with a family history did not seem to depend on the type of abortion. This finding suggests that the effect of a family history on the risk of breast cancer is modified by event(s) resulting from abortions. Further epidemiological studies should be conducted to verify the existence of this interaction.

Abortion, Induced

[Granular cell tumors of the breast].

The granular cell tumor was first described by Abrikossoff who referred to that lesion as myoblastoma. This lesion is mainly observed in soft tissues and is exceptionally found in the mammary gland. Among the 159 cases of breast granular cell tumor reported in the literature, only 121 have been well documented. Tumors occurred in 15 to 74 year old patients and in only 9.8% of the tumors discovered in males. In breast this tumor may mimic a carcinoma like in the three cases reported. The intra-operative diagnosis on frozen sections may be particularly difficult and the risks to overdiagnose a carcinoma are not negligible and must be known. The diagnosis on paraffin sections is much more easier than on frozen sections. The immunostaining procedures (anti p S100) and electron easier than on frozen section. The immunostaining procedures (anti p S100) and electron microscopy are mainly interesting to document the histogenetic hypotheses. The schwannian origin of the tumor is favoured in most of the recent studies. The granular cell tumors are usually benign and malignant tumors account for only 2.5% of those diagnosed in the breast.

Adolescent