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M N Lavaut

Publications and source records attributed to M N Lavaut.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1993

Cathepsin D immunocytochemical assays in breast carcinomas: image analysis and correlation to prognostic factors.

Immunocytochemical assays of cathepsin D were assessed in a series of breast carcinomas (n = 257) using monoclonal M1G8 anti-total cathepsin D and the avidin-biotin-peroxidase complex. Cathepsin immunoreactivity was compared in frozen and paraffin sections. All tumours were anti-cathepsin-positive. Positive staining was observed in carcinoma and stromal cells and in the extracellular matrix. The amount of immunodetectable cathepsin in tissue was measured by computer-assisted image analysis (SAMBA 2005). Both the percentage of immunostained tumour surface and the mean optical densities were processed as continuous variables for statistical analysis and correlated with prognostic factors. It was shown that cathepsin D was independent of the tumour size, the lymph node status, hormone receptors, and pHER-2/neu overexpression. Cathepsin was significantly correlated with anti-EGFR (P = 0.012) and Ki67 (P = 0.002) immunoreactivity, tumour grade (P = 0.032), vascular invasion (P = 0.0081), proliferation index (P = 0.0045), and, to a lesser extent with AgNORs (P = 0.0504) and the degree of hyperploidy (P = 0.057). Tissue fixation and paraffin embedding significantly decreased cathepsin immunoreactivity. These results show that cathepsin D is not a totally independent prognostic factor in breast carcinomas.

Adult↗
PubMed1993

c-myc protein and Ki-67 antigen immunodetection in patients with uterine cervix neoplasia: correlation of microcytophotometric analysis and histological data.

Cone biopsies were carried out in patients (n = 72) with intraepithelial lesions (CIN 1-3) and squamous microinvasive carcinomas of the uterine cervix. Intraoperative histological examination was achieved in order to obtain small cones with healthy upper resection margins. Also, a tissue fragment was sampled and frozen for the immunocytochemical investigations. Image analysis (SAMBA) of immunoprecipitates was used to evaluate c-myc and Ki-67 antigen expression. Positive c-myc protein staining was observed only on microinvasive carcinomas (70%) and CIN 3 lesions (19%) and was correlated with high Ki-67 immunoreactivity. Ki-67 immunostaining was more extensive: (i) in high-grade than low-grade CIN, (ii) in microinvasive carcinomas than in CIN (P < or = 0.01), (iii) in large than in small lesions. No correlation could be found between the levels of either c-myc protein or Ki-67 antigen expression and either patient age or cytological features of HPV infection.

Adult↗
PubMed1993

Epidermal growth factor receptor in breast cancer: correlation of quantitative immunocytochemical assays to prognostic factors.

Immunocytochemical assays for EGFR were performed on frozen sections from breast carcinomas (n = 209). Results were evaluated by computer assisted image analysis to accurately define the percentage of immunostained surface and the mean optical densities. Thirty seven percent (n = 77/209) of the tumors were EGFR positive, but about one third of them were faintly reactive (35%). No significant relationship was observed between EGFR tumor content and patient age, tumor size, histological type, histoprognostic grade, or axillary lymph node status. A negative correlation was observed with the results of estrogen receptor immunocytochemical assays and a positive correlation with immunodetectable cathepsin D and Ki 67 antigen evaluated according the same method. No correlation was found with HER-2/neu protein, aneuploidy, nucleolar organizor region distribution, and nuclear morphometry, also assessed by image analysis. These results suggest that immunocytochemical assays assessed on frozen sections and evaluated by image analysis are suitable for current and standardized evaluation of EGFR which has been previously documented as a prognostic indicator in breast carcinomas.

Adult↗
PubMed1993

Non palpable breast carcinomas. Histological and immunohistochemical studies of 160 cases.

A series of 160 impalpable breast carcinomas was collected from 1979 to 1991. Mammographs showed microcalcifications (64%), or opaque images (36%). Surgical specimens were X-rayed during the intervention in order (i) to ascertain that the lesions detected on mammographs were removed, and (ii) to guide the pathologist in sampling tissue fragment for an appropriate microscopic evaluation of the lesions. During the intervention, the peroperation histological diagnosis was correct in 63% of the cases, whereas malignancies were underscored in 37%. No false positive diagnosis was recorded. A large majority (92%) of false diagnoses stated during surgery were in situ carcinomas diagnosed as epitheliosis and invasive carcinomas diagnosed as in situ carcinomas. In 63% of the cases the axillary lymph node could be removed during the first intervention. In 91% of the cases "in sano" margins of resection were evaluated as such during the intervention. The size of tumors ranged from 1 to 60 mm (m = 10 mm - SD = 8.45), 70% measuring less than 10 mm. Carcinomas were in situ (23.75%), microinvasive (13.75%) and invasive (62.5%). Carcinomas were ductal (78.1%), lobular (18.7%) and of other types (14.2%). A majority of intraductal carcinoma (68%) were comedocarcinomas. Invasive carcinomas accounted for grade I in 37% of the cases, grade II in 56%, grade III in 7%, ductal carcinomas and for tubular carcinomas in 15%. Immunodetection could be performed on frozen sections in 78 cases. Tumors were receptor positive in 58% of the cases. The greater growth fraction (Ki-67) and higher detection of HER-2/neu oncogene product were observed in comedocarcinomas. Diploid tumors accounted for 52% of those evaluated (n = 48).

Adult↗
PubMed1992

Correlation of nucleolar organizer regions and nuclear morphometry assessed by automatic image analysis in breast cancer with aneuploidy, K167 immunostaining, histopathologic grade and lymph node involvement.

Silver-stained nucleolar organizer regions (AgNORs) in human breast carcinoma were studied using a computer-assisted system of image analysis. Standardized, automatic measurements of 7 morphometric parameters (area, perimeter, shape factor, bend energy, angle, and small and large diameters) performed on paraffin sections and cell imprint were compared and correlated with nuclear morphometry, histopathological grading, tumor growth fraction, (monoclonal Ki67-immunostaining), DNA nuclear content (stoechiometric Feulgen staining) and axillary lymph node invasion. The major findings were as follows: (i) variations in AgNORs and nuclear parameters were correlated, (ii) the ratio of AgNOR area/nuclear area was significantly different in low and high grade tumors, (iii) mean AgNOR parameter values increased significantly with the tumor growth fraction and tumor hyperploidy and were significantly higher in patients with axillary lymph node metastases and (iv) AgNOR evaluation was more accurate for cell preparations than for tissue sections.

Antibodies, Monoclonal↗
PubMed1991

Monoclonal 3C6F9 distribution in human breast carcinomas: image cytometry of immunocytochemical assays.

MoAbF9 immunoreactivity was investigated in frozen sections of 123 breast carcinomas using an avidin or streptavidin biotin peroxidase kit. A standardized computer image analysis system was used to evaluate immunostaining. The percent of cell surface staining and mean optical densities were correlated with morphological criteria of prognosis such as tumor size histological grade, blood and lymph invasion and axillary lymph node involvement, with immunoreactivity to other MoAb, i.e. Ki67, anti-RE and anti-RP, anti-p.HER-2/neu and with tumor aneuploidy and AgNORs content in tumor cell nuclei. Despite some heterogeneity, MoAbF9 was reactive with all breast carcinomas tested. The percent of F9 immunostained cell surface and mean optical density increased with Ki67 immunoreactivity, tumor aneuploidy and AgNORs nucleus surface but were independent of p.HER-2/neu oncoprotein distribution and tumor receptor content. These findings suggest that F9 could not only allow detection axillary lymph node micrometastases but also be used as plasmatic marker for tumor recurrence and metastases.

Antibodies, Monoclonal↗
PubMed1991

Fel d I allergen distribution in cat fur and skin.

Immunohistochemical procedures were performed to ascertain Fel d I antigen (Ag) distribution in cat fur and skin biopsy specimens and to analyze Fel d I allergen concentrations in fur. One hundred strands of fur and 24 skin biopsy specimens (6 by 4 by 3 mm) from shaved areas were collected from 11 different cats. Freshly depilated hairs were immunostained by free-floating monoclonal anti-Fel d I, avidin-biotin-peroxidase complex, and either processed for scanning electron microscopic examination or mounted on glass slides for computer-assisted densitometric analysis (SAMBA system). Skin biopsy specimens were promptly frozen and sectioned just before the immunohistochemical processing. Densitometric analysis of fur demonstrated that immunoprecipitate concentrations were tenfold higher at the root than at the tip. However, this finding may be explained by decrease of the thickness of the hair cortex that varied in similar proportions. The Ag accumulated on the strand surface but may focally penetrate into the medulla through the scale-like cortical interstices. In skin biopsy specimens, Fel d I Ag was found in epithelial squamous cells, within the epidermis and hair follicles, on the surface of the epidermis and hair follicles, and in sebaceous gland cells. These data suggest that Fel d I Ag is produced by sebaceous cells and, to a lesser extent, by basal squamous epithelial cells and that it is stored mainly on the surface of the epidermis and fur.

Allergens↗
PubMed1991

Monoclonal antibody 1BE12 immunoreactivity with human endometrium. Correlations with hormone receptors and proliferation cell markers.

The monoclonal antibody (MAb) 1BE12 has recently been reported to react with several human normal and abnormal tissues. In human endometrium, it reacts more strongly with carcinomas than with normal tissue. To investigate the effectiveness of MAb 1BE12 in identifying cell proliferation in human endometrial cancers, 1BE12 immunocytochemical assays (ICAs) were performed on frozen (n = 47) and paraffin (n = 100) sections with subsequent computer-assisted microcytophotometric (SAMBA) evaluation of immunoprecipitate distribution. MAb 1BE12 immunoreactivity was not impaired by tissue fixation and paraffin embedding. It reacted with normal proliferative endometrium but not with normal secretory endometrium, and immunoreactivity increased with the degree of cell proliferation and malignancy, the amount of immunostaining being greater in invasive carcinomas than in normal proliferative endometrium and endometrial hyperplasia. ICAs showed no correlation between MAb 1BE12 immunoreactivity and estrogen and progesterone receptor antigenic sites. On the other hand, MAb 1BE12 staining in frozen sections increased with Ki67, EGFR, pHER-2/neu, and cathepsin immunostaining. These findings suggest that ICAs on frozen and paraffin-embedded biopsy specimens using MAb 1BE12 along with other markers can be useful for early detection and grading of endometrial carcinoma. The relevance of MAb 1BE12 to the selection of patients for laser ablation of the endometrium rather than hysterectomy is also discussed.

Antibodies, Monoclonal↗
PubMed1990

Correlation between laminin and type IV collagen distribution in breast carcinomas, and estrogen receptors expression, lymph node and vascular involvement.

The laminin (Lam) and type IV collagen (Coll IV) and estrogen receptor (ER) immunodetections were assessed in a large series of 400 human breast carcinomas. In all the cases the patient's age, the tumor size, the histological type and grade, the presence or the absence of axillary lymph node metastasis and of vascular invasion in tumor borders, and ER tumor content were recorded. Monoclonal anti-Lam, anti-Coll IV were applied with the avidin-biotin-peroxidase complex and monoclonal anti ER with peroxidase anti-peroxidase complex, on frozen sections. A computerized system of image analysis referred to as SAMBA (TITN) with specific software for tissue sections analysis permitted a multiparametric quantitative analysis of immunostained surfaces. With this system, in each tumor, the cellularity, the percentage of Lam, Coll IV and receptor positive surfaces versus the total cell surface and versus the epithelial (keratin positive) surface, the integrated optical density IOD histograms were obtained and correlated to morphometrical and standard histological data. From this study, it was shown that: (1) Lam and Coll IV immunostained epithelial basement membranes in carcinomas were correlated to the presence of estrogen and progesterone receptor antigenic sites within the tumors, with a significant decrease of the positive staining in ER-ICA negative tumors in comparison to ER-ICA/PR-ICA positive tumors. (2) The combined densitometric and morphometric evaluation demonstrated a decrease of Lam and Coll IV immunostaining in malignant tumors, correlated to (i) the presence of peritumorous vascular invasion and (ii) keratin positive cells in bone marrow (iii) axillary lymph node involvement. It is concluded that the variations in Lam and Coll IV antigens distribution may be relevant indicators of tumor metastatic potential in breast carcinomas and that computerized image analysis enables the standardization of the evaluation antigens distribution.

Adult↗
PubMed1990

Image cytometry of aneuploidy, growth fraction (MoAb Ki-67) and hormone receptors (ER, PR) immunocytochemical assays in breast carcinomas.

DNA nuclear content was assessed in human breast carcinomas (n = 132) using image cytometry. Optical density histograms of Feulgen stained cell imprints from fresh tissue samples, subsequently frozen for immunocytochemical assays, were determined by the SAMBA system and used for the DNA index, the ploidy balance (PB) and the proliferation index (PI) computation. The three parameters were correlated to (i) histological data (tumour grade, vascular and/or lymph node invasion) and to (ii) growth fraction (Ki67), hormone receptor antigenic sites (ER, PR) and intramedullar (bone marrow) biopsies and anti-KL1-positive epithelial cells. It was shown that 57% of breast carcinomas were aneuploid. Aneuploidy PI significantly correlated to the criteria of poor prognosis such as high tumour grade, vascular and lymphatic invasion and to increased Ki67-positive cells, and the absence of or low ER and PR. Since image cytometry is easy to handle and perfectly suitable for current diagnostic practice in pathology departments, particularly for tumour cell ploidy assessment and standardized analysis of immunostaining procedures with morphological control of the preparation, we conclude that image cytometry, as performed with the SAMBA, must be regarded as a relevant tool for prognosis evaluation and therapy guidance in individual patients.

Aneuploidy↗
PubMed1989

Immunodetection in fine-needle aspirates and multiparametric (SAMBA) image analysis. Receptors (monoclonal antiestrogen and antiprogesterone) and growth fraction (monoclonal Ki67) evaluation in breast carcinomas.

Immunocytochemical assays (ICA) using monoclonal antiestrogen receptors (ER ICA), antiprogesterone receptors (PR ICA), and monoclonal antibody Ki67 (Ki67 ICA) were performed in 127 breast carcinomas. The immunostaining procedures were applied on frozen tissue sections, tumour imprints, and fine-needle aspirates in order to compare the variations in the distribution of the antigens detected in the three different types of preparations. Positive reactions detected with peroxidase-antiperoxidase and avidinbiotin-peroxidase, and alkaline phosphatase-antialkaline phosphatase complexes were evaluated through a computerized system of image analysis referred to as SAMBA 200 (SAMBA TITN, Grenoble, France). Application programs specifically developed for the analysis of tissue sections and of cytologic preparations were applied. This system allowed a multiparametric, accurate, reliable, reproducible and automatized evaluation of the heterogeneity of the antigenic sites in tumors. For each markers positive cell surface (PS), and integrated and mean optical densities (IOD, MOD) and IOD histograms were compared. It was shown that (1) there was no significant variation in optical densities in cell imprints and aspirates whereas PS significantly (P less than 0.01) differed in both preparations; (2) there were significant differences of the optical densities between tissue sections and cytological preparations, either imprints or aspirates, likely due to randomly cut nuclei in tissue sections; and (3) there was a significant difference between the PS of tissue sections and aspirates but no significant difference between tissue sections and imprints. It is concluded that fine-needle aspiration constitutes a convenient method for cell sampling, reliable for the diagnosis of malignancies. However, it may not reflect the heterogeneity of cell subpopulations in tissue.

Antibodies, Monoclonal↗
PubMed1989

Immunocytochemical assays in human endometrial carcinomas: a multiparametric computerized analysis and comparison with nonmalignant changes.

Immunocytochemical assay (ICAs) were performed on frozen sections from human endometrial samples (n = 89) including normal endometrium, decidua, hyperplasia with and without atypia, and carcinomas. Monoclonal antiestrogen receptor (ER), anti-laminin (Lam), anti-type IV collagen (Coll IV), and anti-Ki67 were applied with avidin-biotin-peroxidase complex or peroxidase-antiperoxidase complex. The results of the ICAs were evaluated through a computerized system of image analysis referred to as SAMBA. It was shown that this system provided for an accurate reliable and reproducible analysis of ICAs in tissue sections. It is concluded that this multiparametric and standardized method of analysis of ICAs can further be applied in correlations with clinical and biochemical data.

Antigens, Surface↗
PubMed1989

Type IV collagen immunostaining and computerized image analysis (SAMBA) in breast and endometrial disorders.

Type IV collagen immunostaining was performed on tissue sections from a large series of non-malignant and malignant disorders of the breast and endometrium. The results were analysed by means of a computerized system of image analysis referred to as SAMBA. It was shown that this system provided an accurate, reliable, reproducible, automated and multiparameteric analysis of collagen IV immunoprecipitates. It was concluded that this standardized method of analyses can be routinely used for the measurement of collagen IV, thus enabling correlations to be sought with histopathological and clinical data.

Basement Membrane↗
PubMed1989

[Growth fraction (Ki67), ploidy balance and proliferation index in tumors of the urogenital tract and breast].

The practical applications of computer-assisted image analysis systems are multiple in oncology. The computerized system of image analysis referred to as SAMBA (TITN) is particularly relevant to analyse coloured images resulting from immunostaining or histochemical procedures assessed either on tissue sections of any type or cytological preparations (imprints, smears). The SAMBA analysis of positive Ki67 surfaces in tissue sections from breast, endometrial, ovarian, cervical or urinary bladder samples enables a multiparametric evaluation of the growth fraction (GF) in intraepithelial, borderline or invasive proliferations. Moreover, the SAMBA analysis after Feulgen staining procedures provides a parametric evaluation of the nuclei densitometry and morphological features and of the chromatin texture, which serve to compute the ploidy balance (BP) and the proliferation index (PI). In benign tumors, GF and PI are low and tumor cells are diploid with an overall high positive PB values. In malignant tumors, GF, PI and the percentage of aneuploid cells increase with tumor grade and stage whereas PB decreases. In borderline proliferations, FC, PI and PB intermediate values are recorded. These new criteria of prognosis should be assessed routinely in pathology departments and the results from these new investigations are likely to be soon implicated in the selection of patient therapy.

Antigens, Surface↗