Characterization of a new surface epitope specific for human epithelial cells defined by a monoclonal antibody and application to tumor diagnosis.

In an attempt to characterize the antigens attached to cells of a line established from a human squamous cell carcinoma of the tongue (CAL 27), BALB/c mice were immunized with whole CAL 27 cells; hybridomas were then produced using spleen cells of the animals and cells of an NS1 syngeneic myeloma. A hybridoma secreting a monoclonal antibody was obtained (CALAM 27); CALAM 27 was directed against an epitope attached to the CAL 27 cells. CALAM 27, IgG2a, reacted with a membrane antigen specific to all epithelial cells. After immunoprecipitation, this antigen corresponded to two bands (Mr 22,000 and 54,000). Reactivity disappeared when the tissue was embedded in paraffin but was conserved after fixation with acetone or methanol. This antigen was conserved for both benign and malignant epithelial cell pathologies. The action of CALAM 27 was tested on 80 samples of pleural effusions, ascites, and cerebrospinal fluid samples; after conventional cytological examinations, CALAM 27 failed to recognize either reactive mesothelial cells or meningothelial cells. In addition, the cell structure recognized by CALAM 27 is not found on certain lymphoid tissue cells. CALAM 27 also failed to react with small cell carcinoma of the lung. Its strictly epithelial specificity therefore permits its use for the diagnosis of micrometastases of carcinoma in ascites and cerebrospinal fluid, in pleural effusions, and in bone marrow. CALAM 27 may also prove useful in confirming diagnosis of pathologies suspected to be of epithelial origin.

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.

PURPOSE: To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS: Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS: Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION: Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

Cutaneous T-cell lymphoma in association with a monoclonal gammopathy.

Monoclonal gammopathies and other abnormalities of immunoglobulin production may characterize or frequently be associated with B-cell lymphoproliferative disorders. We describe a patient with a T-cell cutaneous lymphoma, expressed clinically as Sézary's syndrome, in association with an immunoglobulin A type kappa M-component monoclonal gammopathy. No evidence for the coincident presence of a malignant plasma dyscrasia was found. This clinical association may lend clinical support to the concept that Sézary's syndrome is a T-helper-cell malignant proliferation. A colonic carcinoma was also present, possibly representing a second manifestation of a functionally abnormal cellular immune system.

A new epithelial membrane antigen (Calam 27) as a marker of carcinoma in serous effusions.

A new monoclonal antibody (Calam 27) that reacts with a membrane antigen present on cells of epithelial origin, but not on cells of mesothelial origin, was investigated as a means of distinguishing between mesothelial cells and malignant cells in cytologic smears of serous effusions from patients with carcinoma. Immunofluorescence staining of cells in 151 effusions from 109 patients with different diseases showed a good correlation between the cytologic diagnosis on routine preparations and the staining with Calam 27. Calam 27 was also used to study the ploidy and cell cycle kinetics of carcinoma cells versus reactive mesothelial cells and normal cells by flow cytometry; these experiments confirmed that Calam 27 is not reactive with mesothelial cells. In conclusion, Calam 27 staining can help to confirm the cytodiagnoses in cases with carcinomatous effusions.

Technical and clinical aspects of cascade filtration plasma exchange (CFPE).

Cascade filtration plasma exchanges (CFPE) were realized using an hemofiltration system (HFS) coupled to 2 filters with different pore sizes. The first one (F1 = plasma-separator; Asahi plasmaflo HI-05) separates plasma from whole blood, the second one (F2 = plasma filter; Asahi XK-60, Kuraray EVAL 2A or 4A) filtrates high molecular weight (MW) components from the separated plasma. F2 filtrate returns to patient mixed with blood cells and 4% Albumin solution or Plasmion R replacing plasma discarded (about 0.5-0.8 I for 1-1.5 plasma mass (PM) treated). The HFS is able i) to modulate the different pressures (venous pressure, F1 and F2 transmembrane pressures (TMp] using pumps speed variators, ii) to recirculate and concentrate extracted plasma and iii) to know F2 treated PM. Blood pressure, pulse rate and electrocardiogram were monitored during each CFPE session. Nineteen CFPE were performed for 8 patients selected among our PE indications, this selection taking into account presence or not of risk factors linked to disease e and/or to patient. Anti-histamine drugs were always infused before CFPE session. On a biological point of view, the problem lies into F2 selectivity which is relatively good for low (as Albumin) and high (as IgM) MW molecules which are returned to patient or discarded, but should be improved for the intermediate ones (as IgG). On a technical point of view, the plasma substitute quantity is reduced about six times. But the control of F2 TMp is not perfectly and the PM to be treated has to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

[Characterization of a human cell line from an anaplastic carcinoma of the thyroid gland]. / Caractérisation d'une lignée cellulaire humaine provenant d'un carcinome anaplasique de la thyroïde.

A new cell line derived from a thyroid anaplastic carcinoma, CAL 62, has been established in culture. This line is constituted by highly tumorigenic cells. Their epithelial phenotype is stable in culture. Immunochemical staining for human thyroglobulin is negative. Cytogenetic analysis showed a gain of chromosome 20, the translocation i (14q), and breakpoints of centrometric chromatine. These results are similar to those previously reported by other investigators. CAL 62 radiosensibility has been studied. The survival curve of the in vitro irradiated cells has been adjusted with a linear-quadratic model. This cell line is thus showed to be radioresistant. Cell line CAL 62 constitutes an appropriate model for in vitro studies of thyroid anaplastic carcinoma.

In vitro clonogenicity in relation to kinetic and clinicopathological features of breast cancer.

The clonogenicity in soft agar and the labeling index (LI) which represents the percentage of cells in the DNA synthesis phase, were studied in 59 breast cancer patients and these parameters were related to other known clinicopathological features, namely age, histological grading, estrogen and progesterone receptors and the status of axillary lymph nodes. Out of 59 tumors, 49 could be successfully cloned in soft agar and the mean plating efficiency (PE) was 0.1%. Low grade tumors were more frequently encountered in tumors which did not form colonies (P = 0.025). Cloned tumors had a higher mean LI (P = 0.05). A high PE was associated with low estrogen receptors (ER) (P = 0.03). Clonogenicity was not related to patient age, progesterone receptors (PR) or the status of axillary lymph nodes. These results suggest that a successful in vitro cloning and a high PE are associated with unfavorable prognostic factors in breast cancer.

[CAL 54, a new cell line derived from a human renal carcinoma: characterization and radiosensitivity]. / CAL 54, une nouvelle lignée cellulaire dérivée d'un carcinome rénal humain: caractérisation et radiosensibilité.

A new cell line (CAL 54) was isolated from a malignant pleural effusion of a patient with renal carcinoma. CAL 54 is a continuous and stable cell line. Immunochemical staining showed simultaneous expression of cytokeratin, epithelial membrane antigen and vimentin. Cytometric flow analysis of DNA content reveals one major hyperdiploid population. Histological aspect of the tumor induced in the nude mouse showed well differentiated adenocarcinoma with papillary structure. Radiation response of these cells was evaluated by the colony-forming method and the data were fitted with the linear-quadratic model. Survival at 2 Gy (SF2) was 0.28 and the mean inactivation dose (D) = 1.50 Gy, ranking this cell line among the radiation sensitive cells. CAL 54 may be an informative cell line to investigate radiation effects in the management of renal tumours.

[Lymphangiosarcoma on a chronic edema of the lower limb. Radiologic study apropos of a case]. / Lymphangiosarcome sur oedème chronique du membre inférieur. Etude radiologique à propos d'un cas.

Lymphangiosarcoma is a rare tumor of the soft tissues, in particular outside of cases where the etiology is represented by chronic edema following mastectomy for breast cancer (Stewart-Treves syndrome). In the case reported, the patient experienced chronic edema of the lower limbs, with diffuse involvement of the right leg. The sonographic appearance revealing thickening of the dermis, with localized infiltration of the aponeurosis, and especially the angiographic findings showing hypervascularization with early venous return are discussed.

[Imaging of non-functional retroperitoneal paragangliomas. Apropos of a case]. / Imagerie des paragangliomes rétropéritonéaux non fonctionnels. A propos d'un cas.

The non functional extraperitoneal paragangliomas are rare tumors (less than 50 cases reported). We report a case with ultrasound and CT scan imaging. The tumor is usually large with important necrotic areas leading to a cystic aspect. The malignant tumors more frequent than the benign tumors present with a regional extension and delayed metastasis.

[Plasma exchange by cascade filtration. Clinical and biological study]. / Echange plasmatique par filtration en cascade. Etude clinique et biologique.

Nineteen double-filtration plasma exchanges were performed in 8 patients selected according to the presence or absence of disease-related and/or patient-related risk factors. The haemofiltration system consists of 2 filters with different pore sizes. The first filter, called plasma separator (Asahi plasmaflo HI-05), separates plasma from whole blood; the second filter, called plasma filter (Asahi XK-60; Kuraray Eval 2A or 4A), separates high molecular weight components from plasma. The filtrate from the second filter is returned to the patient mixed with blood cells and either a 4% albumin solution or Plasmion to replace the plasma discarded (about 0.5-0.8 I for a 1-1.5 plasma mass treated). The system (a) modulates venous pressure and transmembrane pressure in each of the two filters by means of pump velocity variations; (b) recirculates and concentrates the plasma extracted, and (c) provides information on the plasma mass extracted by the second filter. In our study, antihistaminics were always infused before each plasma exchange session, and blood pressure and electrocardiogram were monitored throughout the session. The selectivity of the second filter is relatively good for low and high molecular weight components (e.g. albumin and IgM respectively), but needs to be improved for those of intermediate molecular weight, such as IgG and immune complexes. The amounts of plasma substitute utilized are about 6 times less than with conventional methods; however, transmembrane pressure in the second filter is imperfectly controlled, and this too calls for improvement. A study is in progress to evaluate the ideal plasma mass to be extracted. Clinically, and taking into account the biological results obtained, diseases with high molecular weight mediators should benefit from the double-filtration technique, but this technique needs to be perfected for the treatment of IgG-mediated diseases.

[Cutaneous neuroendocrine carcinoma : apropos of a case]. / Les carcinomes neuro-endocrines cutanés : à propos d'un cas.

A case of neuroendocrine carcinoma (Merkel cell tumor) of the skin in a 76 years old woman is reported. The lesion, an erythematous nodule, 2 to 3 cm in diameter occurred on the face. Light microscopic examination showed sheets of indifferentiated cells that had a uniform round nucleus and scanty cytoplasm containing argyrophil granules. An ultrastructural study demonstrated neurosecretory type granules in the cytoplasm of the tumor cells. Immunocytochemical analysis was strongly positive for neuron specific enolase, but negative for Met-Enkephalin. This case is discussed in the light of a review of 73 cases already published in the literature. The origin of the cells involved in this tumor is still discussed. Several authors have suggested that this tumor is an Apudoma possibly arising from Merkel cells. In most cases, the lesion is an erythematous nodule. The most common localization is the face (45 p. 100). The tumor can be diagnosed by routine histology, but silver staining and electron microscopic study are often helpful. Removal of the tumor should be performed. This tumor appears to be of a low grade malignancy. Local recurrences or metastases have been reported in a few cases.