Expression of new phenotypic markers in cholangiocarcinoma and putative precursor lesions.
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Adenoma, Bile Duct↗
Biomedical subjects
C Patriarca
Publications and source records attributed to C Patriarca.
Patterns of integrin common chain beta 1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size.
Thirty cases of hepatocellular carcinoma (HCC) were investigated immunocytochemically for expression of beta 1 integrin molecule and of collagen IV. Immunoreactivity was related to the tumour proliferation index, as detected by PCNA immunostaining, and to tumour size and grade. Membrane beta 1 integrin immunoreactivity was detected in the neoplastic cells of all cases, though two different staining patterns were clearly recognized. In 14 cases, beta 1 integrin immunoreactivity was confined to the cell-stroma interface, showing the same polarized pattern as the non-neoplastic cell counterpart. This staining pattern was associated significantly (P < 0.0001) with low PCNA labelling (i.e. less than 20 per cent of neoplastic cells showing nuclear immunostaining. Conversely, 16 cases showed non-polarized pericellular beta 1 integrin immunostaining. This staining pattern was significantly associated (P < 0.0001) with high PCNA labelling (more than 20 per cent of immunoreactive cells) and with tumour size greater than 4 cm in diameter (P < 0.0001). beta 1 Integrin, collagen IV, and PCNA immunoreactivities, however, did not correlate with the histological grade. The data emphasize that neoplastic progression of HCCs may be correlated with an aberrant expression of adhesion molecules and with a disruption of the collagen IV complement of basal membranes.
Antigens, Neoplasm↗
Popliteal lymph node response to procainamide and isoniazid. Role of beta-naphthoflavone, phenobarbitone and S9-mix pretreatment.
The popliteal lymph node assay (PLNA) was proposed for the preclinical prediction of xenobiotics-induced autoimmune reactions in humans. Among the substances so far tested in this model, procainamide and isoniazid gave negative PLNA responses despite reports of lupus syndromes in man. To confirm the hypothesis that a metabolite instead of the parent molecule is involved, rats were pretreated with phenobarbital or beta-naphthoflavone, then injected with procainamide or isoniazid. In additional groups of animals, procainamide or isoniazid were injected together with S9-mix following various incubation times. Pretreated rats had a positive PLNA response when injected with procainamide, whereas preincubation with S9-mix resulted in a positive response to isoniazid. These results further support the validity of the PLNA.
Animals↗
Well-differentiated neuroendocrine carcinoma of the lung: a clinicopathologic and ultrastructural study of 10 cases.
The clinico-pathologic characteristics of 10 resected pulmonary tumors, which proved to be well-differentiated neuroendocrine carcinomas (WDNC) on the basis of light microscopic, immunocytochemical, ultrastructural and immunoelectron microscopic investigations, were evaluated. The tumors showed a wide spectrum of histologic features that could be referred to three basic patterns: 1) a carcinoid-like pattern; 2) an organoid pattern characterized by palisading cells at the edge of cellular areas, and 3) a prevalent adenocarcinoma-like pattern. The second pattern was the most distinct even though it often mimicked the small cell/large cell subtype of small cell carcinoma (SCC) owing to its association with marked atypia and poor differentiation. All but one of the patients were males and smokers. The mean age was 58 years. Half of the tumors were centrally located including those showing the adenocarcinoma-like pattern. Disease-free and overall survival and type of tumor dissemination in four patients were similar to those of SCC. Five evaluable patients were alive and disease-free after a mean follow-up of 74 months. Two of these were initially diagnosed as SCC. We conclude that, because of its impact on prognosis, the diagnosis of WDNC appears to be relevant although other factors able to adversely affect the clinical course remain undefined.
Adenocarcinoma↗
Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine popliteal lymph node (PLN) test.
Time-related and dose-related popliteal lymph node (PLN) enlargement and lymphocyte subset alterations owing to subcutaneous (s.c.) injection of streptozotocin (STZ) into the foot pad were determined in (C57BL/6 x DBA/2)F1 [B6D2F1] mice. Early cell activation and time-related changes in T and B lymphocyte subsets were monitored during the onset of STZ-induced lymphoproliferative reaction by flow cytometry and immunophenotyping of lymphocyte subsets stained with a panel of monoclonal antibodies. Examination of cell size and chromatin decondensing for T and B cell subsets revealed differences in their activation profiles during the early phase of STZ-induced lymph node enlargement. The kinetics of the reaction showed initial activation and proliferation of CD4+ cells associated with accumulation of CD8+ and B cells. Subsequently CD8+ cells were activated and proliferated, but there was no evidence of early or late B cell activation as shown by the lack of increase in cell size or nuclear decondensation and the low and transient synthesis of immunoglobulins. The activation characteristics for CD4+ and CD8+ cell subsets in STZ-induced node enlargement were found to be analogous with T cell activation in acute allogeneic graft-versus-host (GVH) reaction in which the F1 recipient differed from the parent at both class I and II MHC loci. Our data support a central role for T cell activation in the induction of STZ-related PLN enlargement and suggest that recirculatory host B cells can play a major role in early node enlargement.
Animals↗
A cystic partially differentiated nephroblastoma producing alpha-fetoprotein.
A case of cystic partially differentiated nephroblastoma with immunohistochemical and serological demonstration of alpha-fetoprotein (AFP) production is described. To our knowledge, this is the first such case reported. The morphological heterogeneity of this rare tumor led us to describe the criteria of its nosological classification and of its differential diagnosis with intrarenal teratoma. AFP, besides being a marker of germline-derived tumor, was associated to this rare variant of Wilm's tumor. Although the tumor did not show regression either on clinical or pathologic assessments, serum AFP levels decreased after preoperative chemotherapy and returned to normal limits after nephrectomy.
Biomarkers, Tumor↗
Popliteal lymph node assay as a tool to predict drug-induced GvH-like reactions.
The popliteal lymph node (PLN) assay was proposed to study a panel of drug-induced clinical manifestations, e.g. lupus syndrome, serum sickness-like disease, lymphadenopathy, scleroderma-like reaction, the mechanism of which was suggested as being similar to a graft-versus-host (GvH) reaction, hence the term GvH-like reaction. This assay can readily be performed in either the mouse or rat. The commonest endpoint is PLN weight, but cellularity and lymphocyte-phenotype analysis can also be determined. Experiments so far show that most drugs and chemicals known to induce such complications in man can be detected by the PLN assay and false-positive responses are extremely few. Interestingly, preliminary results indicate that cimetidine, an immuno-enhancing agent, can increase the response to phenytoin, a positive reference compound in the PLN assay. Thus, in addition to predicting those drugs with the capacity to induce GvH-like reactions and investigating the mechanism involved, the PLN assay may also prove useful in the pre-clinical assessment of immunomodulating agents.
Animals↗
Well-differentiated neuroendocrine carcinoma of the lung: a case report.
Well-differentiated neuroendocrine carcinoma (WDNC) of the lower respiratory tract displays clinical and radiologic features intermediate between carcinoids and small cell carcinoma and shares some biologic characteristics with both. We describe a case of WDNC resistant to three different treatments. The patient, a 42-year-old woman, received 2 cycles of chemotherapy before coming to our observation, including cyclophosphamide, adriamycin and vincristine, with progression of disease. We administered r-alpha-2a interferon for 2 months, but the patient showed clinical progression. Therefore, streptozotocin associated with epirubicin was utilized, but the patient died of disease progression after 4 cycles and 10 months from the first treatment. The case of WDNC described in this report showed an unusual aggressive clinical course and was refractory to conventional and unconventional treatments. The proper management for WDNC is still unknown. However, according to literature data, the chemotherapeutic schemes employed for small cell lung cancer represent the first treatment choice for WDNC. Further studies are needed to help define treatment strategies according to the biology of the tumor.
Adult↗
Prognosis of resected well-differentiated neuroendocrine carcinoma of the lung.
Among lung tumors, well-differentiated neuroendocrine carcinomas are often misdiagnosed or may go unrecognized. Nineteen cases of well-differentiated neuroendocrine carcinoma (WDNC) were assessed at the National Cancer Institute of Milan over a ten-year period. There was only one woman and the age range was 50 to 77 years. Most of the patients were smokers (83 percent). All tumors were radically resected. There were 12 lobectomies, two sleeve-lobectomies, three bilobectomies, one pneumonectomy, and two segmentectomies (one patient had two synchronous WDNCs). There was neither operative mortality nor major complications. Sixteen tumors were stage 1, three were stage II, and one was stage IIIa. Five patients had adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine [CAV] regimen). One patient was given local or regional radiotherapy. In ten patients the tumors recurred, even though four had had adjuvant treatment. The brain was the first site of metastasis in seven cases. The pathologic stage seemed not to be closely related to the appearance of metastases (six patients with stage I disease had recurrences). Only two patients with recurrence were still alive 12 and 103 months after the procedure. The percentage of survival for patients with stage I disease after more than 100 months was 68 percent. WDNC is similar to small-cell lung carcinoma (SCLC) with regard to the neurotropism of metastases. Surgery is curative for more than one half of the patients with localized disease. Therefore, multimodal therapy, probably based on tumor behavior and investigations of tumor markers, is advisable.
Carcinoid Tumor↗
Silver enhancement of nickel-diaminobenzidine as applied to single and double immunoperoxidase staining.
A reliable and practical method is proposed for increasing sensitivity and detection efficiency of immunocytochemical techniques, based on silver enhancement of the nickel-diaminobenzidine product of the peroxidase reaction. The procedure produces a strong signal at the site of the end product of the peroxidase reaction which is visible as black grains at the light microscopic level. The method has been used to detect peroxidase labeled probes in immunocytochemical tissue preparations and blotting assays and is ideal for the purposes of double staining and photographic documentation.
3,3'-Diaminobenzidine↗
Expression of two antigens defined by monoclonal antibodies in normal, benign and malignant human mammary tissues.
We examined the reactivity of two monoclonal antibodies (MAbs), MBrI and MBr8, on sections from normal breast tissues, benign lesions, primary infiltrating carcinomas and distant breast cancer metastases and compared the expression of the recognized antigens (CaMBr1 and CaMBr8 respectively) in these different normal and pathologic conditions. The expression of both antigens was found to significantly decrease in the neoplastic tissues, in comparison to normal breast tissue (34% vs 61% for MBr1 and 52% vs 86% for MBr8; p less than 0.001 for both). Atypical epithelial hyperplasia was found to be reactive on the same level (31%) of the tumors when tested with MBr1, whereas its reactivity was similar to that of normal tissues (78%) when MBr8 was used. Nonatypical epithelial hyperplasia showed the same reactivity with both MAbs (positive staining on about 50% of the cells). 65% of the "in situ" ductal carcinoma cases was MBr1-positive, whereas 50% was MBr8-positive; these values, when compared with the reactivity on normal glands, were significantly lower for MBr8, but not for MBr1. When testing sections from premenopausal women who had biopsies performed on different days during their menstrual cycle a correlation was found between the expression of CaMBr1 in normal breast epithelial cells and the stimulatory phase of the cycle. These findings suggest that both antigens are typical of normal breast and their expression could possibly decrease in pathologic tissues.
Antibodies, Monoclonal↗
Relationship between CaMBr1 expression and tumor progression in small cell lung carcinomas.
In order to study the possible relationship between antigenic phenotype and tumor progression, 63 small cell lung carcinomas (SCLC) biopsies derived from primary or metastatic tumors were tested by immunofluorescence and immunoperoxidase techniques with an anti-carcinoma monoclonal antibody designated MBr1. Primary tumors were found to be less reactive with MBr1 than the local and distant metastatic lesions (57% versus 75% and 89% positivity respectively). A life table analysis on the tested cases indicated an inverse association between the expression of the marker recognized by the MBr1 MAb (CaMBr1) and overall survival (p less than 0.01): patients with MBr1-positive tumors showed a shorter survival time in comparison to patients whose tumors did not express the marker. The same correlation between survival and CaMBr1 expression was found even when only the 31 cases of early stage disease patients were considered (p less than 0.05). Different tumor aggressiveness or resistance to therapy of MBr1-positive tumors could be responsible for the shorter survival time of the patients.
Antibodies, Monoclonal↗
Progesterone receptor determination in human breast tumors by immunocytochemical and biochemical techniques.
Progesterone receptors were determined on frozen sections from 74 primary human breast tumors by an immunocytochemical assay using an indirect avidin-biotin peroxidase method. In the same tumors, cytosol estrogen (ERc) and progesterone receptors (PgRc) were determined by ligand binding assay, and nuclear estrogen (ERn) and progesterone receptors (PgRn) were determined by an immunoassay. Immunocytochemical staining was seen in 36% of tumors. It was predominantly nuclear and there was extensive cell to cell heterogeneity. When the immunocytochemical results were compared to PgRc the agreement rate was 63%, but it was 77% when compared to PgRn. About one third (38%) of PgRc positive tumors were immunocytochemically defined as negative. Thus a significant discordance exists between this immunocytochemical assay for PgR and both the conventional radioligand assay (used for PgRc) and the relatively new enzyme immunoassay (used for PgRn). However discordance rates were critically influenced by the arbitrary cutoff levels that were used to define receptor positivity in the biochemical assays. Our studies support the addition to, rather than the substitution of, immunocytochemical methods, to the conventional biochemical assays for PgR, until long-term follow-up studies of patients with PgRn and immunocytochemical PgR determinations become available.
Breast Neoplasms↗
Incompatibility of morphine sulfate and prochlorperazine edisylate in syringes.
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Chemistry, Pharmaceutical↗
Oral specific hyposensitization in the management of patients allergic to food.
Results are presented of a protocol of hyposensitizing treatment per os in 19 cases of food allergy (allergy to milk in 8, to egg in 8, to fish in 2, and to orange in one). Treatment, performed in the out-patients service, was successful in 14 out of the 15 patients who followed it correctly (i.e. 93.3% of cases). Treatment lasted between 3 and 12 months.
Adolescent↗
Depolarized expression of episialin (EMA, MUC1) in lung adenocarcinoma is associated with tumor progression.
Carcinoma cell detachment is an important step in tumor progression and metastasis. Episialin (EMA), if expressed throughout the entire cell surface, may inhibit cell-cell and cell-matrix adhesion. We investigated whether the cellular distribution of episialin in non-small cell lung cancer (NSCLC) is associated with tumor progression. We evaluated the expression of episialin by immunohistochemical staining, in surgical specimens from 122 adenocarcinomas and 99 squamous cell carcinomas. Episialin was present in most NSCLC, with a higher percentage of immunoreactive neoplastic cells in adenocarcinoma than in squamous cell carcinoma (p = 0.0001). In adenocarcinoma the depolarized pattern was significantly associated with nodal metastasis (p = 0.005) and with advanced stage (p = 0.007). In conclusion, nodal metastasis and advanced pathological stage in adenocarcinoma are associated with a depolarized cellular distribution of episialin, suggesting a possible involvement of the molecule in cancer metastasis.
Adenocarcinoma↗