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M J Lacombe

Publications and source records attributed to M J Lacombe.

At least 19 recordsLinked to original sources
PubMed2001

Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma.

HLA-G is a nonclassical class I antigen mainly expressed at the maternofetal interface during pregnancy where it is thought to down-modulate maternal immune response against the semiallogeneic fetus. Recent studies indicate that ectopic up-regulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antigen is differentially expressed in carcinoma and normal renal cells and that up-regulation of this antigen in the tumor cells is more frequent than alterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response in vitro, we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.

Adult↗
PubMed2001

Upregulation of alpha(8)beta(1)-integrin in cardiac fibroblast by angiotensin II and transforming growth factor-beta1.

Using a novel pharmacological tool with (125)I-echistatin to detect integrins on the cell, we have observed that cardiac fibroblasts harbor five different RGD-binding integrins: alpha(8)beta(1), alpha(3)beta(1), alpha(5)beta(1), alpha(v)beta(1), and alpha(v)beta(3). Stimulation of cardiac fibroblasts by angiotensin II (ANG II) or transforming growth factor-beta1 (TGF-beta1) resulted in an increase of protein and heightening by 50% of the receptor density of alpha(8)beta(1)-integrin. The effect of ANG II was blocked by an AT(1), but not an AT(2), receptor antagonist, or by an anti-TGF-beta1 antibody. ANG II and TGF-beta1 increased fibronectin secretion, smooth muscle alpha-actin synthesis, and formation of actin stress fibers and enhanced attachment of fibroblasts to a fibronectin matrix. The alpha(8)- and beta(1)-subunits were colocalized by immunocytochemistry with vinculin or beta(3)-integrin at focal adhesion sites. These results indicate that alpha(8)beta(1)-integrin is an abundant integrin on rat cardiac fibroblasts. Its positive modulation by ANG II and TGF-beta1 in a myofibroblast-like phenotype suggests the involvement of alpha(8)beta(1)-integrin in extracellular matrix protein deposition and cardiac fibroblast adhesion.

Angiotensin II↗
PubMed1995

In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma.

Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infiltrated by a large mononuclear infiltrate mainly composed of T lymphocytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) alpha and beta chains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined V alpha and V beta gene segment usage by PCR using a panel of V specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). A highly diverse usage of TCR V alpha and V beta gene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed V beta specificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with V beta 4 transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed V beta transcripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in V beta 4) specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens.

Adult↗
PubMed1990

Experience with renal transplantation in the second and third decades at the Hennepin County Medical Center.

Approximately one-third of the patients receiving renal transplants have functioning allografts at 10 years. Chronic rejection continues to be the leading cause of kidney loss in late survivors. Atherosclerotic cardiovascular disease, liver failure, malignancy, and sepsis are the major causes of late death. Identification and control of the risk factors contributing to patient mortality should enhance the long-term success of renal transplantation.

Female↗
PubMed1989

Human breast tumors: a comparison between the biochemical method of measuring estrogen and progesterone receptors and that of an immunohistochemical method.

In a series of 94 human mammary carcinomas, the determination of total estrogen (ER) and progesterone (PR) receptors by a single saturating dose method (5 nM for ER, 10 nM for PR) using dextran-coated charcoal was compared to an immunohistochemical method utilizing ER monoclonal antibody (ER-ICA test). There was a good correlation expressed in positive terms between the ER-ICA test and the biochemical determination of ER (94% of concordance) with a statistical value of P less than 0.01 being found between the concentration of ER (biochemical) and the percentage of labeled cells (ER-ICA). The ER-ICA test complements the ER and PR (biochemical) and is particularly useful for ER determinations on small tumor specimens as no additional tissue other than that from the biopsy is required.

Breast Neoplasms↗
PubMed1988

Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inflammatory stroma.

The hallmarks of diagnosis of medullary breast cancer (MedBC) used by the authors since 1977 have been that the tumor is well circumscribed, has syncytial architecture in greater than 75% of its surface, contains diffuse inflammatory infiltrate, has atypical nuclei, and forms no glandular pattern. In order to assess the clinical utility of these criteria, we studied a series of 95 previously untreated, surgically operable patients with breast carcinoma at the Institut Gustave-Roussy (IGR) between 1960 and 1979. A diagnosis of MedBC was initially made for these patients or suspected based on abundant inflammatory stroma observed in a histologic evaluation. Using these criteria, 26 cases were identified as typical medullary carcinoma (TMC), 23 cases as atypical medullary carcinoma (AMC), and 46 cases as nonmedullary carcinoma (NMC). The 26 cases of TMC represent a very small fraction of the total infiltrating operable breast carcinomas diagnosed at IGR during the same time period. The prognosis for these 26 patients was much more favorable than for the other groups. They had a 10-year disease-free survival of 92% compared with 53% for the AMC group and 51% for the NMC group. Neither distant metastasis nor secondary primaries of the same histology were seen. Therefore, it is possible with the use of strict histologic criteria to distinguish a group of patients with a much more favorable prognosis. This histologic diagnosis alone renders a most favorable prognosis for the patient even if other factors such as large tumor size and lymph node involvement are present and, by inference, the only therapy needed is the removal of all tumor. In contrast, atypical forms have a prognosis no different from other atypical types of breast carcinomas without inflammatory stroma, and adjuvant therapy appears to be justified if other factors warrant it.

Breast Neoplasms↗
PubMed1988

Malignant peripheral neuroectodermal tumours of bone other than Askin's neoplasm: characterization of 14 new cases with immunohistochemistry and electron microscopy.

Peripheral neuroectodermal tumours (PNET) of bone are rare and mimic those seen in soft tissue (peripheral neuroepithelioma of soft tissue). Their differential diagnosis from Ewing's sarcoma (Es) is extremely difficult by optical means. Here we report 14 new cases of PNET of bone (other than Askin's neoplasm) located primarily in the limbs, pelvic girdle and scapula. Clinically and radiologically they displayed Ewing's sarcoma-like features: mean age was 14.4 years, male/female ratio being 3:11. Metastasis was present in 6 cases at diagnosis (5 with bone metastasis). Prognosis was poor; thirteen patients died; only one with a metatarsal located tumour is alive and free of disease. The mean survival rate was 25 months following diagnosis and treatment with radio- and multimodal chemotherapy. Histologically the 14 cases displayed Homer-Wright rosettes and pseudorosette-like structures, as well as a fibrillary background and lobular pattern. Immunohistochemistry revealed positivity in a number of neural markers when using paraffin-embedded material: NSE, B-2-microglobuline, HNK-1 (leu-7) and E-36 antibodies. At EM level the cell cytoplasms evidenced dense-core granules with neurosecretion, neurotubules and intermediate filaments like those seen in peripheral neuroepithelioma.

Adolescent↗
PubMed1987

Small round blue cell sarcoma of bone mimicking atypical Ewing's sarcoma with neuroectodermal features. An analysis of five cases with immunohistochemical and electron microscopic support.

Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a dense chromatine pattern and the presence of isolated dendritic processes, as well as synaptic-like buttons; intermediate filaments, neurotubuli, and dense-core neurosecretory granules also were seen. Moreover, in two cases basement-like condensations surrounded some cells. Scanning electron microscopic study in one case confirmed the presence of rosette-like figures and cell elongations with short dendritic projections of the cytoplasm. Clinically and radiologically these cases showed features similar to ES of bone; one case, located in the chest wall, had a local relapse after treatment, with the histologic features of a pleomorphic neuroblastoma. The authors conclude that these tumors resemble closely immature neuroepithelioma of soft tissue but, being primary to bone, are superimposable on those described as "neuroectodermal tumors of bone."

Antibodies, Monoclonal↗
PubMed1987

Immunohistochemical distribution of the 52-kDa protein in mammary tumors: a marker associated with cell proliferation rather than with hormone responsiveness.

We have previously described a secreted glycoprotein of mol. wt 52,000 (52-kDa protein) which is induced by estrogen in some human breast cancer cell lines. This protein has been identified as the proenzyme of a lysosomal cathepsin-D-like protease which is secreted in large proportions in breast cancer cells. To determine which information may be generated by this marker when detected in mammary tumors, in comparison with hormone receptors, we used monoclonal antibodies interacting specifically with the 52-kDa protein and its related cellular processed products (mols. wts 48 and 34 kDa). A high concentration of this protein has been shown in proliferative ductal mastopathies and cysts, suggesting its value in detecting high-risk mastopathies. We now present the immunoperoxidase distribution of this protein in breast carcinoma compared to the cytosolic hormone receptors assayed in parallel. In 232 breast cancers, no correlation was found between the cellular 52-kDa protein content and cytosolic estrogen or progesterone receptor concentrations. This absence of correlation was also shown by the constitutive production of this protein by estrogen-receptor-negative breast cancer cell lines and confirmed by double immunostaining of breast cancer cell aspirates showing a dissociation between the cytoplasmic staining of this 52-kDa lysosomal protease and the nuclear staining of the estrogen receptor. These clinical results, associated with the in vitro mitogenic and proteolytic activities of this protein, strongly suggest that the 52-kDa protein staining in tissue is associated with tumor proliferation and/or invasion, rather than with hormone responsiveness.

Antibodies, Monoclonal↗
PubMed1987

Musculoskeletal tumors: follow-up with MR imaging after treatment with surgery and radiation therapy.

Magnetic resonance (MR) imaging was used as a follow-up technique in 60 patients who underwent surgery and/or radiation therapy for primary malignant musculoskeletal tumors. MR imaging was performed on a 1.5-T imager with T1- and T2-weighted imaging sequences; MR imaging findings were confirmed by means of posttreatment surgery and histologic analysis or follow-up for at least 1 year. If a low-signal-intensity lesion was seen on T2-weighted images in a patient who had undergone radiation therapy or surgery, the patient usually did not have active tumor (sensitivity, 96%). If a high-signal-intensity lesion was seen after a patient had undergone only surgery, the patient had active tumor (six of six such cases). In patients who had undergone only radiation therapy, however, the presence of a high-signal-intensity lesion may indicate either active tumor or radiation-induced inflammatory changes. Thus, in such cases, differential diagnosis of active tumor may be difficult, if not impossible, to make from MR images.

Bone Neoplasms↗
PubMed1987

[Definition and anatomo-pathologic classification of benign breast diseases].

Most pathological changes in the mammary gland that are not tumours are fibrocystic diseases. Their classifications, at first purely descriptive, can now be used to predict the risks of cancer. All the same, there is no real parallel between these classifications and the difficulties in differential diagnosis that these lesions present for the pathologist. This is so true that the risk has to be defined by more objective markers than one morphological finding.

Breast Diseases↗
PubMed1987

[The role of the pathologist in the treatment of osteogenic sarcoma].

The pathologist today has an important role in the treatment of osteosarcoma. He contributes during the operation by advising about the extent of the tumour and after the operation by studying the operative specimen to assess the extent of the tumour, and, when primary chemotherapy has been used, to estimate the effectiveness of the treatment by counting the percentage of viable tumour cells so that the type of chemotherapy used subsequently can be adapted to the situation. Only trained teams can make the best use of these studies.

Humans↗
PubMed1986

Histopathological predictive factors in Ewing's sarcoma of bone and clinicopathological correlations. A retrospective study of 261 cases.

A retrospective multifactorial analysis on 261 previously untreated patients with Ewing's sarcoma (Es) of bone has been carried out in order to ascertain the prognostic value of several histological variables on survival. Among those cases accepted as Es, 208 (80% of the patients) were considered to be "typical Es", while 40 (15%) displayed a large cell predominance, being subclassified as "atypical large cell Es". Furthermore, 13 patients (5%) possessed tumours of endothelial-like appearance. Eleven cases which displayed a mixed histological configuration were finally included within one of the three previous groups according to their predominant histological pattern. After adjustment for therapeutic regimens and initial location of the tumour, only two histological characteristics remain significant; i.e. the presence of necrosis (p = 0.002) and, to a lesser degree, the presence of filagree "en damier" pattern (p = 0.08), both of which are of poor prognostic value. From this study, it can be assumed that the morphological (and possibly histogenetical) heterogeneity of Es of bone has no prognostic influence on survival.

Bone Neoplasms↗
PubMed1986

[Fibroadenoma of the breast with atypical clear-cell epithelial hyperplasia. Apropos of 7 cases. Immunohistochemical study].

We report 7 cases of unusual fibroadenomas of the breast. They are characterized by an exuberant cellular proliferation within the ductal lumens. They appear in young women from 20 to 40 years old. These lesions are histologically identical to those described by Azzopardi (1979) under the name of "Argyrophilic cells in fibroadenomas" and by Eusebi and Azzopardi (1980) and by Govoni (1981) and called "Lobular endocrine neoplasia in fibroadenoma of the Breast". An immunohistochemical study reveals a major positivity of these cells, in all cases, with Antikeratin Antibody (anti Kl1) and with Epithelial Membrane Antigen (anti EMA) proving the epithelial origin of these cells. There cells cannot yet be regarded as belonging to the neuro-endocrine group, because of the negativity, in all cases of Grimelius and Bodian stains, and of the very heterogeneous positivity observed with Neuron-Specific Enolase antibody (anti NSE) and with anti Human Natural Killer antibody (anti HNK). These cellular proliferations seem to us, on the microscopical point of view related to the atypical epithelial hyperplasias of the breast, and different from the in situ lobular carcinoma. Thus we propose to call these lesions "variant of the breast fibroadenoma" characterized by an atypical epithelial clear cell hyperplasia. The treatment of these lesions merely consists of a lumpectomy. Only one case is associated with an eleven years free of disease follow-up: a follow-up comprised between on to fifteen months is observed in the others cases. The knowledge of these benign lesions appears to us very important, to avoid improper treatment caused by an erroneous diagnosis of carcinoma developing in a breast fibroadenoma.

Adenofibroma↗
PubMed1986

[Estrogen receptors in cancer of the breast. Comparison of 2 methods].

The dosage of estrogenic receptors (ER) was performed on 80 cytosols of human breast carcinomas "immediately operable", by using a methode consisting of a single saturating dose (5 nM) with carbon-dextran and a new immuno-enzymatic method commercialized by ABBOTT laboratories using anti-ER monoclonal antibodies. The concordance is excellent between the two methods in terms of positivity. The results are significantly higher with the ER-IEA method than with the biochemical method (p. less than 1.10(-5]. The regression of the ER-IEA method as compared to the biochemical method is linear with a regression line: Y (ER-IEA) = 0.82 X (ER-Biochem) + 0.76 (logo10 conc. fmoles/g tissue). The correlation is good between the two methods (r = 0.90). A significant relationship (p less than 0.01) has also been observed with the histological grade of the carcinoma. Finally, the immuno-enzymatic technique seems particularly well adapted to small biopsies and slightly positive tumors.

Antibodies, Monoclonal↗
PubMed1985

The response to initial chemotherapy as a prognostic factor in localized Ewing's sarcoma.

Ninety-five children with localized Ewing's sarcoma were included in a prospective cooperative study. All patients received initial chemotherapy with the purpose of early prevention of metastases and improvement of the conditions of the subsequent local therapy, radiotherapy in all cases, surgical resection in selected cases. Clinical response to initial chemotherapy was evaluated in 67 patients who had measurable soft tissue mass or functional symptoms. This response appeared highly correlated with outcome as the disease-free survival was 57.3% for the 41 good responders and 9% for the 26 bad responders (P less than 0.00001), though 23 of these bad responders reached complete remission with radiotherapy. This study also confirms the prognostic significance for survival of the site of the primary tumor on axial skeleton or on limbs. Nevertheless, this factor had no predictive value for response to chemotherapy, which thus appears to be an independent factor.

Adolescent↗