Biomedical subjects

G Arrigoni

Publications and source records attributed to G Arrigoni.

At least 19 recordsLinked to original sources

PubMed2006

Analysis of a sub-proteome which co-purifies with and is phosphorylated by the Golgi casein kinase.

In an attempt to gain information about the identity of the Golgi apparatus casein kinase(s) (G-CK), responsible for the phosphorylation of caseins in lactating mammary gland, the proteins present in fractions enriched in G-CK activity eluted from DEAE-Sepharose and heparin-Sepharose columns were resolved by two-dimensional electrophoresis and analyzed by mass spectrometry. This led to the identification of 47 proteins altogether, none of which is a bona fide protein kinase. At least 9 of the identified proteins however, are readily phosphorylated by co-purifying G-CK activity, and 7 are physically associated with it to give supramolecular complex(es) of about 500 kDa as judged from Superdex S200 gel fitration and glycerol gradient ultracentrifugation experiments. In contrast, the apparent molecular weight of G-CK estimated from an in gel activity assay after SDSPAGE and renaturation is about 41 kDa. Many of the proteins phosphorylated by and/or associated with G-CK belong to the category of chaperonines, including HSP90, GRP-94 and -78, and various isoforms of protein disulfide isomerases, suggesting a global role of this kinase in the modulation of protein folding.

Amino Acid Sequence↗

PubMed2005

Protein kinase CK2 phosphorylates and upregulates Akt/PKB.

Treatment of Jurkat cells with specific inhibitors of protein kinase CK2 induces apoptosis. Here we provide evidence that the anti-apoptotic effect of CK2 can be at least partially mediated by upregulation of the Akt/PKB pathway. Such a conclusion is based on the following observations: (1) inhibition of CK2 by cell treatment with two structurally unrelated CK2 inhibitors induces downregulation of Akt/PKB, as judged from decreased phosphorylation of its physiological targets, and immunoprecipitate kinase assay; (2) similar results are observed upon reduction of CK2 catalytic subunit by the RNA-interference technique; (3) Akt/PKB Ser129 is phosphorylated by CK2 in vitro and in vivo; (4) such a phosphorylation of activated Akt/PKB correlates with a further increase in catalytic activity. These data disclose an unanticipated mechanism by which constitutive phosphorylation by CK2 may be required for maximal activation of Akt/PKB.

Amino Acid Sequence↗

PubMed2004

Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma.

BACKGROUND: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. PATIENTS AND METHODS: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. RESULTS: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) > 1; 21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 +/- 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage I), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS < or = 1, disease limited to the skin, stage I, and use of chemotherapy were independently associated with better outcome. CONCLUSIONS: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features.

Adult↗

PubMed2002

Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are rare tumors, mostly represented by diffuse large B cells. PCNSLs with a T phenotype are less frequently reported; even rarer are anaplastic large cell lymphomas (ALCLs). PCNSL ALCLs are commonly represented, like their systemic counterpart, by a variably prevalent amount of large pleomorphic tumor cells ('hallmark cells'), and this feature enhances their recognition. Patient and methods We report the first case of primary brain CD30+ ALK-1+ ALCL with a T-cell phenotype, showing the combination of both the 'lymphohistiocytic' and the 'small cell' variants of the disease. A few elements consistent with 'hallmark cells' were recognizable. However, these cells were never prominent, increasing diagnostic difficulties. Immunohistochemistry results were critical for the correct interpretation. Our findings also differ from the majority of PCNSL ALCLs for the absence of tumor necrosis and the lack of prominent mitotic activity. The neuroimaging picture was not specific. A comparison with literature data concerning the clinical/instrumental features shows a very frequent meningeal involvement in PCNSL ALCLs, in contrast to the majority of PCNSLs. CONCLUSION: The occurrence of such a rare form of ALCL may widen the spectrum of differential diagnoses in PCNSL and their recognition may allow a rapid diagnosis, thus encouraging adequate treatment, which should take into account the high rate of meningeal involvement observed in these cases.

Adult↗

PubMed2001

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.

3T3 Cells↗

PubMed2001

The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.

HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a G(i/o) protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.

Animals↗

PubMed2001

Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma.

OBJECTIVE: The incidence of adenocarcinoma and bronchoalveolar carcinoma has increased in recent years. The aim of this study was to retrospectively evaluate radiological and pathological factors affecting survival in patients with bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who underwent surgical treatment. METHODS: From May 1988 to September 1999, 49 patients with BAC or BAC and adenocarcinoma underwent surgical treatment. Complete resection was performed in 42 patients. In these patients the impact of the following factors on survival was evaluated: stage, TNM status, radiological and pathological findings (percentage of bronchoalveolar carcinoma in the tumour, presence or absence of sclerosing and mucinous patterns, vascular invasion and lymphocytic infiltration). RESULTS: Twenty-nine patients were male and 20 female. Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the patients who underwent complete resection demonstrated a favourable impact on survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients with stage Ia and Ib disease, univariate analysis demonstrated that the absence of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01) favourably influenced survival. The latter data were also confirmed by multivariate analysis (P = 0.01). CONCLUSION: Surgical treatment of early-stage BAC and combined BAC and adenocarcinoma is associated with favourable results. However, the definition of prognostic factors is of utmost importance to improve the results of the treatment. In our series tumours of the mucinous subtype and with a lower percentage of BAC had a worse prognosis.

Adenocarcinoma↗

PubMed2001

Maspin and mammaglobin genes are specific markers for RT-PCR detection of minimal residual disease in patients with breast cancer.

BACKGROUND: This study evaluates the specificity of some reverse-transcriptase polymerase chain reaction (RT-PCR) assays for the detection of residual tumor cells in breast cancer patients. The following markers have been analysed: carcinoembryonic antigen (CEA), cytokeratins (CK19 and CK20), polymorphic epithelial mucin (MUC-1), epidermal growth factor receptor (EGFR), maspin, and mammaglobin. RT-PCR was employed to detect breast cancer cells in peripheral blood (PB), bone marrow (BM), and stem cell leukoaphereses (PBPC). PATIENTS AND METHODS: We evaluated the specificity of our RT-PCR assays on a panel of breast cancer specimens (n = 30), on PBPC in patients undergoing high-dose chemotherapy (n = 38), on BM (n = 7) and PB (n = 5) samples obtained from patients with breast cancer. Marrow cells, PB, and PBPC from normal subjects or hematological tumor patients were tested as negative controls. RESULTS: Only maspin and mammaglobin met the criteria of sensitivity and specificity required for the detection of residual disease; they were expressed in 80% and 97% of breast cancer specimens, respectively, and not expressed in normal controls. CK19, CK20. EGFR, MUC-1, and CEA were sometimes expressed in normal blood cells and/or hematological tumors. CONCLUSIONS: Our data support the notion that maspin and mammaglobin are useful markers for RT-PCR detection of minimal residual disease (MRD) in breast cancer patients, and that perspective clinical studies are needed to determine wether RT-PCR assays will be useful in assessing prognosis, tailoring therapy, or developing new strategies for ex vivo purging.

Biomarkers, Tumor↗

PubMed2001

The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics.

In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3, CCR4, and CCR8 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC), and I-309. We have studied the expression of chemokines and chemokine receptors in the airway mucosa of atopic asthmatics. Immunofluorescent analysis of endobronchial biopsies from six asthmatics, taken 24 hours after allergen challenge, demonstrates that virtually all T cells express IL-4 and CCR4. CCR8 is coexpressed with CCR4 on 28% of the T cells, while CCR3 is expressed on eosinophils but not on T cells. Expression of the CCR4-specific ligands MDC and TARC is strongly upregulated on airway epithelial cells upon allergen challenge, suggesting an involvement of this receptor/ligand axis in the regulation of lymphocyte recruitment into the asthmatic bronchi. In contrast to asthma, T cells infiltrating the airways of patients with chronic obstructive pulmonary disease and pulmonary sarcoidosis produce IFN-gamma and express high levels of CXCR3, while lacking CCR4 and CCR8 expression. These data support the role of CCR4, of its ligands MDC and TARC, and of CCR8 in the pathogenesis of allergen-induced late asthmatic responses and suggest that these molecules could be considered as targets for therapeutic intervention.

Asthma↗

PubMed2000

Mediastinal dumbbell angiolipoma.

Nonneurogenic dumbbell tumors are rare. This report describes the case of a 46-year-old woman with a symptomatic mediastinal dumbbell angiolipoma. The tumor was successfully resected using a single-stage procedure, combining a posterior microneurosurgical and thoracoscopic approach. The patient made an uneventful recovery and the neurologic symptoms improved immediately.

Angiolipoma↗

PubMed2000

Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis.

Intravascular Lymphomatosis (IL) is a rare and usually aggressive form of non-Hodgkin's lymphoma characterized by the growth of neoplastic cells within vascular lumina that usually presents with skin or central nervous system (CNS) involvement. The mechanism(s) for the selective intravascular growth of this neoplasm remain(s) unexplained. We now report clinical and immunohistologic data on surgical material from 6 cases of IL; in 4 of 6 cases, autopsies were performed. Our IL cases shared the following features: (1) B-cell lineage; (2) lack of skin involvement at presentation; (3) aggressive behavior; and (4) lack of extravascular lymphomatous masses; in addition, 1 case had an associated gastric low-grade MALT lymphoma. We studied by immunohistochemistry formalin-fixed, paraffin-embedded sections with monoclonal antibodies to molecules known to be involved in lymphocyte and endothelial adhesion phenomena, that is, CD29 (beta1 integrin subunit), CD43 (leukosialin), CD44 (H-CAM), CD54 (ICAM-1), embryonal N-CAM (e-NCAM), and EMA (episialin). In all cases, the surfaces of IL aggregates reacted for CD44 but were consistently negative for CD29; also absent was CD54. Conversely, the integrity of the endothelial cells was underscored by their even reactivity for CD29, CD44, and CD54. Given that CD29 is currently regarded as critical for lymphocyte trafficking in general and for transvascular migration in particular, and CD54 is also involved in transvascular lymphocyte migration, we conclude that their consistent absence in IL may contribute to its intravascular and disseminated distribution pattern. The rather frequent association of IL with various conventional lymphomas is known; yet, one of our cases appears to be the first report of IL associated with a low-grade MALT lymphoma.

Aged↗

PubMed2000

Diagnostic and therapeutic management of neuroendocrine lung tumors: a clinical study of 44 cases.

Neuroendocrine tumors of the lung (NTL) are a distinct subset of tumors with a wide range of histological patterns and clinical behavior. Controversy still exists as to the ideal diagnostic and therapeutic approach to these neoplasms. A series of 44 consecutive NTL patients operated on at our Institution was retrospectively reviewed in order to critically analyze the diagnostic and therapeutic management. A preoperative diagnosis was obtained in 11 patients (25%). All patients underwent an anatomical surgical resection with lymphoadenectomy. Pathological diagnosis was typical carcinoid (TC) tumor in 36 cases, atypical carcinoid (AC) in three and large-cell neuroendocrine carcinoma (LCNEC) in five. One patient had preoperative chemotherapy. Node-positive patients received postoperative radiotherapy on the mediastinal area. Median follow-up time was 40 months for TC and 51.5 months for AC/LCNEC. Recurrence of disease was observed in three patients with TC and in two with AC/LCNEC. Actuarial 5-year survival was 93% for TC and 70% for AC/LCNEC. Survival was not influenced by tumor size, while lymph node metastases were associated with a worse prognosis. However, due to the limited number of patients, no statistical significance was observed. In conclusion, our study confirms findings in the literature showing that TC and AC/LCNEC are clinically different, and that a differential preoperative diagnosis and treatment is necessary. Although the results of new diagnostic techniques such as octreotide scintigraphy are encouraging, they need to be validated in a larger number of patients. Surgery, with anatomical resection and lymphoadenectomy, remains the treatment of choice in all these tumors. Laser treatment should be considered only as a palliative procedure or as a complementary technique to surgery. The role of adjuvant treatments in AC and LCNEC is uncertain and should be evaluated in larger trials. The prognostic role of biological factors such as cytometry and genetic markers requires further investigation before any definitive conclusions can be drawn.

Adolescent↗

PubMed1998

Cell loss and proliferation in non-small cell lung carcinoma: correlation with histological subtype.

BACKGROUND: Cell kinetic data are important indicators of the aggressiveness of tumor and treatment response. The size of a neoplasm depends on the balance between cell proliferation and death. Thus, the analysis of the kinetics of cell proliferation and death may explain differences in the rates of tumour progression. METHODS: We studied apoptosis and proliferative indices in 95 cases of non-small cell lung carcinomas. The analysis was performed on paraffin-embedded tissue, by both MIB-1 immunocytochemical detection to establish the proliferation index and the in-situ end labelling method for the apoptosis index. The two indices were related. RESULTS: Our results showed a high proliferative index and cell loss rate in squamous cell carcinoma, and a low proliferative index and cell loss rate in adenocarcinoma, suggesting two different growth patterns. CONCLUSION: These findings could explain the different biological behaviour and treatment response of the tumours. The tendency of a cancer cell to undergo apoptosis may be especially important for the chemotherapy of malignant tumours with a low growth rate, which are typically resistant to cytostatic agents.

Apoptosis↗

PubMed1996

Carotid atherosclerosis. Immunocytochemical analysis of the vascular and cellular composition in endarterectomies.

Papers dealing with rupture of carotid plaque surface are few in spite of the growing importance of the subject. The aim of this study was to analyze the cellular and vascular components of surgically excised carotid endarterectomies in order to obtain information about their role in the pathogenesis of the plaque rupture and intraplaque hemorrhage. Seventy-six surgical specimens of carotid endarterectomies were used for this study. The findings of immunophenotyping of the cellular constituents of the plaques were: 1) endothelial lining: the fibrous cap at the site of the rupture showed an eroded surface with loss of the endothelial lining. Conversely, in the remaining surface a continuous, not damaged row of endothelial cells stained with anti-CD31 and anti-CD34 was observed; 2) fibrous cap: the collagenous fibrous cap at the site of erosion was attenuated and the phenotypic characterization of the cells showed inflammatory components consisting mainly of macrophages (CD68 positive), 2/3 of the total infiltration. The remaining 1/3 was composed of T-lymphocytes and scarce B-lymphocytes. A close interaction between macrophages and capillaries and macrophages and T-lymphocytes was observed; 3) lipid cores: two different types of lipid cores could be depicted. Avascular or mildly vascularized lipid cores and highly vascularized, with neoformed vessels stained with CD34 and CD31. CD34 stained endothelia of all kind of vessels; conversely, neoformed vessels showed a weak stain with CD31. T-lymphocytes were found to be in close contact with neoformed vessels, and in some cases, migrating through the endothelial cells; 4) deeper layers of the plaque: the base and the shoulder of the plaques showed in 28/76 cases neoformed vessels, thin or thick walled, CD34 positive, generally surrounded by mild to extensive mononuclear infiltrates. Atherosclerotic plaques were found to belong to six different lesions: plaque rupture plus thrombosis (18/76, 23.6%), plaque rupture plus intraplaque hemorrhage plus thrombosis (18/76, 23.6%), intraplaque hemorrhage without plaque rupture (16/76, 21.0%), plaque rupture plus intraplaque hemorrhage (5/76, 6.5%), stable calcified non complicated plaque (14/76, 18.4%) and unstable, soft, non complicated plaque (5/76, 6.5%). The first four lesions were considered as "complicated lesions". Complicated plaques presented neoformed vessels in the periphery, shoulder and base of the plaque in 22/57 (38.5%) cases. Conversely only 1/14 (7.1%) of non complicated, stable calcified plaques presented neoformed vessels, (p < 0.05). Of note, the 5 causes of unstable, soft non complicated plaque presented neoformed vessels surrounding the plaque. In 10/57 (17.5%) complicated plaques unequivocal histological signs of old hemorrhages were found surrounding those vessels. Irrespective of presenting no rupture, 11/35 plaques showed a mononuclear infiltrate in the fibrous cap. In conclusion, rupture of carotid plaques (50% of the cases), is characterized by the presence of a macrophagic infiltration of the caps and by the direct apposition of T-lymphocytes to macrophages and a close relation of these cells to endothelial cells. This highly suggests a cell-to-cell interaction, which results in an inflammatory process. Intraplaque hemorrhage without rupture represented 21% of the endarterectomies. These lesions are not related to cap erosion, but to plaque vascularization. Most lipid cores were highly vascularized with neoformed vessels with macrophages and T-cells in close contact and in some cases disrupting the endothelium. The abrupt growing of the lipid core and/or an overproduction of oxygen free radicals could lead to the breakdown of core vessels and intraplaque hemorrhage.

Adult↗

PubMed1994

Primary gastric CD30 (Ki-1)-positive large cell non-Hodgkin's lymphomas. A clinicopathologic analysis of six cases.

BACKGROUND: The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and frequently involving the skin and other extranodal sites. In cutaneous large cell lymphomas, the CD30 expression was indicated as a favorable prognostic marker independently from cytology, anaplastic versus nonanaplastic. The stomach is the most common site of extranodal lymphomas in the adult population, but primary gastric CD30+ lymphomas have been reported rarely. METHODS: The clinical, morphologic, and immunohistochemical features of six cases with primary CD30/Ki-1+ gastric large cell lymphomas were analyzed. RESULTS: The mean age of patients was 64 years with a prevalence of women (M:F ration = 1:2). Patients were assigned to Stage IE or IIE. Three of them died of disease, whereas the others are still alive (mean follow-up, 18 months). Three of six cases had ALCL morphology, whereas other cases had centroblastic, immunoblastic, and high-grade mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B-cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and a null, non-B, non-T phenotype in two of six cases. CONCLUSIONS: Within CD30+ primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic, did not affect clinical presentation and/or prognosis. The survival rate of the patients studied is in keeping with literature reports regarding prognosis of primary high-grade gastric NHL. The findings suggest that clinical behavior of this extranodal lymphoma is more closely related to clinical symptoms and initial stage of disease than to CD30 expression.

Adult↗

PubMed1993

Longitudinal transgastric echocardiographic views utilizing a single-plane probe: anatomic correlations and clinical applications.

In order to widen the diagnostic capability of single-plane transesophageal echocardiography, which has been so far confined to transverse imaging planes, we obtained four transgastric longitudinal echocardiographic views which have not been previously described. These views can image structures such as superior and inferior vena cava, the right ventricular inflow and outflow tract, the mitral apparatus and the ascending aorta, which are poorly visualized by transesophageal transverse single-plane echocardiography. Among 400 consecutive patients these scans gave relevant additional diagnostic information in 62 cases (15.5%) and provided the correct diagnosis in 37 (9.2%). There were no complications related to the longer gastric manipulation of the probe and the quality of the images was high. We conclude that longitudinal echotomographic scanning of the heart is not exclusively confined to the use of biplane or omniplane probes, but longitudinal views can be consistently obtained with a single-plane instrument.

Aorta↗

PubMed1992

Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms.

Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA-labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi-quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.

Antigens, Neoplasm↗

PubMed1992

Cytogenetics of multiple endocrine neoplasia syndromes. I. Two different, unique clonal chromosome changes in a medullary thyroid carcinoma and in a C-cell thyroid hyperplasia.

In short-term cultures of tumor tissue from a medullary thyroid carcinoma (MTC), we found a large clone of cells with a balanced translocation t(9;12)(p24;q22). A large clone with a balanced translocation t(10;16)(p11;q24) was also found in cultures from a C-cell thyroid hyperplasia. No clearcut evidence for chromosome instability was observed in the lymphocytes of the two patients. The mother of the first patient died of MTC; two relatives of the second patient had MTC and one of them had pheochromocytoma. These findings classify the two subjects as MEN 2A patients with different phenotypic expression but with the same type of chromosomal abnormality.

Adult↗