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Biomedical subjects

C Charpin

Publications and source records attributed to C Charpin.

At least 55 records · Page 3Linked to original sources

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↗

[Morphometry by analysis of microcalcifications and histopathological diagnosis: a new approach to the diagnosis of impalpable lesions of the breast detected by mammography].

A series of 104 impalpable breast lesions detected by mammograms containing microcalcifications was studied. Intraoperative radiographs of intact and sliced specimens were assessed, followed by microscopic diagnostic on frozen sections of areas containing microcalcifications. Microcalcification detected on mammograms and on radiographs of the specimens were digitized and evaluated according morphometric parameters including the mean surface, shape factor, bend energy, the envelope surface and the total surface, the total number and the concentration of the microcalcifications. Benign disorders, atypical hyperplasia and carcinomas accounted for 47.2%, 4.8% and 48% of the tissue lesions respectively, but disorders were most often heterogeneous and mixed. Most but not all parameters were significantly correlated in the three types of radiographs, although radiographs of the sliced specimens provided for images of the best quality. Only two parameters, the mean size and the bend energy were significantly (p = 0.008, p. = 0.036) different in benign and malignant lesions. It is concluded that image analysis of digitized microcalcifications in radiographs may provide a quantitative basis helpful for mammograms interpretation.

Breast↗

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↗

Effects of castration and testosterone on Fel dI production by sebaceous glands of male cats: II--Morphometric assessment.

A morphometric study of cat sebaceous glands was performed to evaluate the effects of castration and testosterone treatments. Skin biopsies were taken in six cats before castration, after castration and after the testosterone injections administered after castration (total number of biopsies: 18). Ninety 8 microns thick sections of each biopsy were assessed for image analysis processing (SAMBA 2005, ALCATEL TITN). The variations in glands and cells size were evaluated on digitized microscopic images by morphometric parameters included in the SAMBA software package. An original software was developed for the analysis of the spacial gland structure. The best morphometric parameters were selected in a first step of the study, and included the nuclear surface (NS), the cell surface (CS) and the nuclear/cellular surface ratio (N/C). These three parameters were then compared in each group of samples for the six cats. It was shown that after castration the N/C (21%) significantly increased compared with prior to castration (12.6%). This 59.8% increase was mainly due to cell cytoplasm shrinking reflecting a decrease of the cell activity. The testosterone administered after castration produced a reverse effect with a N/C ratio back to normal (11.4%) and a significant cell cytoplasm and gland enlargement as shown by the three dimension constructions. This morphometric data correlated with the measurement of sebum and Fel dI productions. The negative effects of castration and the positive effects of testosterone on the sebaceous cells and glands volume favour the hypothesis that cat sebaceous cells are subject to hormonal control this is also likely to apply to the Fel dI production.

Allergens↗

[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↗

[Molecular markers in breast cancer: practical aspects and morphologic evaluation].

The evaluation of molecular markers in breast carcinomas can be routinely assessed by (i) histochemistry for ploidy measurement (Feulgen stain) and for AgNORs counts, and by (ii) immunocytochemistry (Ki67, cathepsin D, pHER-2/neu, EGFR, ER, PR, pS2, p53). Immunocytochemical assays are correlated to biochemical assays and are particularly relevant in small tumors in which only small amount of tissue is available. Immunocytochemical assays provide for data additional to current histological methods, useful for prognostic evaluation and for the selection of node negative patients who may benefit from adjuvant therapy. Nevertheless, immunocytochemical assays can be used for clinical purposes only if they are standardized (frozen sections, image analysis).

Adult↗

[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↗

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↗

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↗

Uterine angiomyolipoma associated with pregnancy.

Uterine angiomyolipomas are rare lesions composed of mature adipose tissue, smooth muscle, fibrous connective tissue, and blood vessels in varying proportions. We reported the first case of angiomyolipoma associated with a normal pregnancy. Initially, the tumor developed intramurally and could have been confused with a partial molar gestation. After delivery, tumor development was extensive and subserosal, making differential diagnosis from a sarcoma difficult. The question of histological diagnosis, as well as that of immunocytochemical analysis which seems to be helpful in such cases, is discussed here.

Adult↗

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↗

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↗

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↗

Fel d I allergen: skin and or saliva?

To determine the relative importance of saliva and sebaceous glands as sources of Fel d I allergen, we compared Fel d I levels at the base and tip of the hair in areas presenting more or less sebaceous glands and areas licked more or less frequently. The amount of Fel d I was significantly higher at the base than the tip of the hair. Further, it was strongly correlated with the density of sebaceous glands. This study demonstrated that the most abundant source of Fel d I allergen is cat skin.

Allergens↗

Inflammatory carcinoma of the breast.

Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months.

Adult↗

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↗