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Luigi Insabato

Publications and source records attributed to Luigi Insabato.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic value of p27Kip1 expression in Basaloid Squamous Cell Carcinoma of the larynx.

BACKGROUND: Very few reports have investigated the role of cell cycle regulators as biomarkers in Basaloid Squamous Cell Carcinoma (BSCC) of the larynx, a definite morphologic, uncommon, very aggressive variant of squamous cell carcinoma. Lower expression of Ki67/Mib-1, a proliferation marker highly expressed in the majority of tumours, and p53, a tumour suppressor protein that can induce an arrest of the G1-S transition, was related to a better prognosis in laryngeal BSCC. In the head and neck, p27kip1, a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors, has emerged as an independent prognostic factor, able to identify low-expressing tumours with unfavourable course. Up to date the role of this protein was never studied in BSCC. Aim of our study was to investigate the potential prognostic value of p27kip1 levels and their correlation with Ki67/Mib-1 and p53 expression in BSCC of the larynx. METHODS: The retrospective study group consisted of 15 male and 1 female patients, affected by laryngeal BSCC, ranging in age from 44 to 69 years (mean 58). The tumour originated from the supraglottis in thirtheen cases and from the glottis in the remaining three. Ten patients had metastatic cervical lymph nodes at presentation and were classified as N+. Post surgical stage was IV in four patients, III in nine, II in two cases and I in the remaining one. Follow-up ranged from a minimum of 5 months up to 9 years. Paraffin-embedded tissue sections of each laryngeal tumour were analyzed for p27kip, Ki67/Mib-1 and p53 expression by immunohistochemistry. RESULTS: The immunohistochemical study showed p27kip1 expression in 40% of the patients with no evidence of disease (NED) and in none (0%) of the patients dead of disease (DOD), whilst p53 was expressed in 60% of patients in NED status and in 90% of patients in DOD status. Ki67/Mib-1 was positive in 80% of NED patients and in 100% of DOD patients. At multivariate analysis, performed by means of Discriminant analysis, low levels of p27kip1 expression significantly correlated with poor prognosis (P < 0.05). CONCLUSION: p27kip1 protein has been shown to be a significant independent prognostic factor in laryngeal SCC. In our series of laryngeal BSCC the resulting data seem to confirm the clinical prognostic relevance of p27kip1 low expression, which directly correlated with biological aggressiveness and consequent shortened survival.

Adult↗
PubMed2006

Endocervical metaplasia of the endometrium in a patient with cystic fibrosis: a case report.

OBJECTIVE: To report the case of an infertile female patient with cystic fibrosis who was diagnosed with endocervical metaplasia of the endometrium at diagnostic hysteroscopy and successfully treated with an oral estroprogestinic formulation. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 27-year-old infertile female patient with cystic fibrosis. INTERVENTION(S): Hysteroscopy with multiple random biopsies was performed at the time of the first visit and after a 10-month cycle with an oral estroprogestinic formulation. MAIN OUTCOME MEASURE(S): Hysteroscopic evaluation with target biopsy; histological examinations of endometrial specimens. RESULT(S): Our patient benefited from a 10-month cycle with an oral estroprogestinic formulation. At the control visit we noticed a significant improvement in the hysteroscopic appearance of her endometrium, and the histological examination confirmed the complete reversion of the metaplastic alterations previously observed. CONCLUSION(S): The present report suggests a novel histological alteration possibly involved in affecting fertility in women with cystic fibrosis. In addition, the positive response to the estroprogestinic treatment observed in our patient poses new questions regarding the relationship between ovarian hormones and cystic fibrosis transmembrane conductance regulator protein regulation, offering interesting perspectives for a hormonal therapy in the treatment of subfertility in women with cystic fibrosis.

Administration, Oral↗
PubMed2005

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report.

BACKGROUND: The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. CASE PRESENTATION: The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. CONCLUSION: This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

Aged↗
PubMed2005

Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors.

PTEN/MMAC1/TEP1: (hereafter PTEN) is a tumor suppressor gene (located at 10q23) that is frequently mutated or deleted in sporadic human tumors. PTEN encodes a multifunctional phosphatase, which negatively regulates cell growth, migration and survival via the phosphatidylinositol 3'-kinase/AKT signalling pathway. Accordingly, Pten+/- mice develop various types of tumors including teratocarcinomas and teratomas. We have investigated PTEN expression in 60 bioptic specimens of germ cell tumors (32 seminomas, 22 embryonal carcinomas and six teratomas) and 22 intratubular germ cell neoplasias (ITGCN) adjacent to the tumors for PTEN protein and mRNA expression. In total, 10 testicular biopsies were used as controls. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not an early event in testicular tumor development. The loss of PTEN expression occurs mainly at the RNA level as determined by in situ hybridization of cellular mRNA (17/22) but also it may involve some kind of post-transcriptional mechanisms in the remaining 25% of cases. Analysis of microsatellites D10S551, D10S541 and D10S1765 in GCTs (n=22) showed LOH at the PTEN locus at 10q23 in at least 36% of GCTs (three embryonal carcinoma, three seminoma, two teratoma); one seminoma and one embryonal (9%) carcinoma presented an inactivating mutation in the PTEN gene (2/22). Finally, we demonstrated that the phosphatidylinositol 3'-kinase/AKT pathway, which is regulated by the PTEN phosphatase, is crucial in regulating the proliferation of the NT2/D1 embryonal carcinoma cells, and that the cyclin-dependent kinase inhibitor p27(kip1) is a key downstream target of this pathway.

Animals↗
PubMed2005

Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study.

Despite clearly defined histologic criteria, the prediction of tumor behavior for patients with gastrointestinal stromal tumors (GIST) still poses a challenge to pathologists. Therefore, searching for alternative markers that allow for better prognostic evaluation is an important task. To determine the practicability of immunohistochemical staining for p16 in clinical cases, we examined p16 protein expression in a group of 284 GISTs, a subset of which had long-term follow-up (median, 45 months; range, 1-204 months). P16 protein expression was ascertained on tissue microarrays as well as on standard sections. Survival analyses were carried out in 157 patients. P16 loss was found in 50% of GISTs, there being no correlation with age, sex, histologic subtype, signs of necrosis, or metastases. Patients having p16-negative tumors had a worse prognosis than those with p16-positive tumors (P = 0.012) with a 2.3-fold relative increased risk of dying of disease. P16 loss identified a subgroup of gastric tumors with a worse prognosis (P = 0.03). The multivariate configural frequency analysis identified two "antitypes," whose observed frequency was found to be significantly lower than the expected frequency [i.e., marker combinations: p16 positive, no metastases, and death of disease and p16 loss, metastases, and still alive]. The "type" whose observed frequency was significantly higher than the expected frequency consisted of the following marker pattern: p16 loss, necrosis, and death of disease (P < 0.001). In the multivariate Cox regression analysis, p16 loss, necrosis, and metastases each had independent prognostic value. P16 loss is a common molecular abnormality in GISTs and might be used in routine diagnosis to identify patients with high-risk tumors.

Adolescent↗
PubMed2005

Patterns of gene amplification in gastrointestinal stromal tumors (GIST).

Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal tumors of the gastrointestinal tract (GIT). They represent a wide clinico-pathological spectrum of tumors. No single histological or clinical parameter can predict the prognosis while the response to therapy is related to the type of KIT or PDGFRA mutation. Cytogenetic and CGH studies have identified frequent gross chromosomal aberrations but the target genes of these changes are unknown. To determine whether known oncogenes take part in genomic rearrangements and to investigate the potential clinical significance of their amplifications, nine known oncogenes (CMYC, MDM2, GLI1, CDK4, HER2, EGFR1, CCND1, FGF3, EMS) were analyzed by fluorescent in situ hybridization (FISH) on a tissue microarray (TMA) containing 94 primary GIST. Clinical follow-up information was available for 57 of these patients. Amplification was found for CMYC in three of 90 (3.3%), for MDM2 in five of 94 (5.3%), for EGFR1 in five of 94 (5.3%), and for CCND1 in seven of 79 (8.9%) evaluable cases. No amplifications were seen for HER2, GLI1, CDK4, FGF3, and EMS. Amplifications of MDM2 and CCND1 were associated with clinical and histological malignancy. In conclusion, our data show that gene amplification does occur in a subset of GIST. Identification of MDM2/CCND1 amplification may represent another molecular feature that could help in the evaluation of the behavior of GISTs.

Adult↗
PubMed2004

Giant cell tumor and Paget's disease of bone in one family: geographic clustering.

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone.

Aged↗
PubMed2004

Malignant gastrointestinal leiomyosarcoma and gastrointestinal stromal tumor with prominent osteoclast-like giant cells.

CONTEXT: One case of leiomyosarcoma and one case of gastrointestinal stromal tumor with prominent osteoclast-like giant cells have so far been reported in the digestive tract. OBJECTIVE: To ascertain the clinicopathologic features and biologic behavior of these tumors, we report 3 additional cases of leiomyosarcoma of the gastrointestinal tract and one malignant gastrointestinal stromal tumor. DESIGN: Histologic and immunohistochemical examinations were performed. Clinical and follow-up data were recorded, and the literature was reviewed. RESULTS: The age of the patients ranged from 50 to 68 years (mean, 62 years). One of the lesions arose in the stomach, one in the ileum, and 2 in the colon. Three tumors showed a strong positivity for muscle actin and desmin and were diagnosed as leiomyosarcomas, 2 of them showing spindle cells and 1 of them showing epithelioid cells. The fourth tumor reacted strongly positive for c-Kit (CD117) and vimentin, and it was diagnosed as an epithelioid malignant gastrointestinal stromal tumor. All tumors were characterized by numerous osteoclast-like giant cells that were unevenly distributed and that, using immunohistochemistry, reacted strongly with CD68. CONCLUSIONS: Malignant stromal tumors with osteoclast-like giant cells of the gastrointestinal tract are rare entities, are more commonly of a myogenic origin such as leiomyosarcoma, and seem to have an aggressive behavior.

Actins↗
PubMed2003

Clinicopathologic and immunohistochemical study of surgically treated primary gastric MALT lymphoma.

BACKGROUND AND OBJECTIVES: B-cell MALT lymphoma is a well-recognized entity and its characterization as low-grade (LG) and high-grade (HG) lymphoma has been widely accepted. In the present study we reviewed a series of 95 surgical specimens of primary gastric MALT lymphoma selected between 1979 and 1998. Immunohistochemical expression of p53, bcl-2, and Ki67 and Helicobacter pylori (Hp) infection was evaluated, along with a correlation with clinical outcome. METHODS: A morphologic and immunohistochemical analysis, including p53, bcl-2, and Ki67 expression, was carried out in all cases. A complete follow-up was obtained in 49 patients and in these cases a survival analysis was performed. RESULTS: bcl-2 protein was highly expressed in 25 of 25 assessed LG tumors and in 20 of 24 assessed HG tumors. p53 protein was expressed in 13 of 25 assessed LG tumors and in 21 of 24 assessed HG tumors. High proliferation rate as expressed by Ki67 was detected in 15 of 25 assessed LG tumors and in 23 of 24 assessed HG tumors. Hp infection was detected in 11 of 16 assessed LG tumors and 2 of 10 assessed HG tumors. Median survival rates were 72 months for LG tumors and 24 months for HG tumors. CONCLUSIONS: A significant inverse relationship between Hp infection and histological grade was found. High p53 expression and high-proliferation rate correlated with HG tumors. However, a correlation between p53, bcl-2, and Ki67 expression with clinical outcome was not found.

Adult↗
PubMed2003

Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is absent in the skeletal muscle of DMD patients and mdx mice. At the plasma membrane of skeletal muscle fibers, dystrophin associates with a multimeric protein complex, termed the dystrophin-glycoprotein complex (DGC). Protein members of this complex are normally absent or greatly reduced in dystrophin-deficient skeletal muscle fibers, and are thought to undergo degradation through an unknown pathway. As such, we reasoned that inhibition of the proteasomal degradation pathway might rescue the expression and subcellular localization of dystrophin-associated proteins. To test this hypothesis, we treated mdx mice with the well-characterized proteasomal inhibitor MG-132. First, we locally injected MG-132 into the gastrocnemius muscle, and observed the outcome after 24 hours. Next, we performed systemic treatment using an osmotic pump that allowed us to deliver different concentrations of the proteasomal inhibitor, over an 8-day period. By immunofluorescence and Western blot analysis, we show that administration of the proteasomal inhibitor MG-132 effectively rescues the expression levels and plasma membrane localization of dystrophin, beta-dystroglycan, alpha-dystroglycan, and alpha-sarcoglycan in skeletal muscle fibers from mdx mice. Furthermore, we show that systemic treatment with the proteasomal inhibitor 1) reduces muscle membrane damage, as revealed by vital staining (with Evans blue dye) of the diaphragm and gastrocnemius muscle isolated from treated mdx mice, and 2) ameliorates the histopathological signs of muscular dystrophy, as judged by hematoxylin and eosin staining of muscle biopsies taken from treated mdx mice. Thus, the current study opens new and important avenues in our understanding of the pathogenesis of DMD. Most importantly, these new findings may have clinical implications for the pharmacological treatment of patients with DMD.

Animals↗
PubMed2003

Anasarca caused by Cryptococcus neoformans after heart transplantation.

Cryptococcosis is an opportunistic infection caused by the yeast-like fungus Cryptococcus neoformans. The infection predominantly strikes patients with cell-mediated immunodeficiency, that is, patients with organ transplants, leukemia, lymphoma, AIDS, and those receiving steroids or immunosuppressants. We describe a patient with skin lesions and anasarca secondary to intestinal infection from Cryptococcus neoformans after heart transplantation. We based diagnosis on histologic examination of the cutaneous lesions and of the duodenal mucosa. This case demonstrates that in immunosuppressed patients with anasarca of unknown origin, a diagnosis of intestinal opportunistic infection also should be considered.

Cryptococcosis↗
PubMed2003

Ovarian metastasis from renal cell carcinoma: a report of three cases.

Ovarian metastases from renal cell carcinoma (RCC) are very rare. Over the past 16 years we have encountered 3 examples. The first 2 cases occurred in adults 49 and 50 years old, respectively, who had huge ovarian metastases, clinically detected 12 and 14 months, respectively, after diagnosis of RCC. The third case was a 17-year-old girl in whom a metastatic renal cell carcinoma was detected in an otherwise benign-appearing cystic ovarian mass. To the best of our knowledge only 11 cases of clinically detected ovarian metastases of RCC have been reported. We report 3 new cases and review the literature on the subject.

Adenocarcinoma, Clear Cell↗
PubMed2002

Solid-pseudopapillary tumor of the pancreas: a neoplasm with distinct and highly characteristic cytological features.

The solid-pseudopapillary tumor of the pancreas (SPTP) is an unusual low-grade malignant epithelial tumor affecting predominantly adolescent girls and young women. Although approximately 500 cases of SPTP have been described in the last 40 yr, its pathogenesis remains uncertain. However, the clinical features of this neoplasm are very characteristic and SPTP must be suspected in any young woman with a cystic or partially cystic pancreatic mass. In this report, we describe the cytologic features of seven cases of SPTP investigated by preoperative fine-needle aspirates. The analysis of the cytologic features in these cases and in 43 cases collected from the literature reveals that they are highly characteristic and quite distinct from those of other cystic or solid tumors of the pancreas. On this basis, a cytologic diagnosis of SPTP may be rendered with great confidence, not only in clinically typical examples, but also in unusual presentations, such as in older patients, in males, in ectopic locations, and in metastatic sites.

Adolescent↗
PubMedDate not supplied

Massive infarction of papillary carcinoma of the kidney after fine needle aspiration biopsy: report of a case with cytohistologic correlation.

BACKGROUND: Papillary carcinomas are rare malignant tumors of the kidney that sometimes are diagnosed preoperatively from their characteristic computed tomography appearance. CASE: A patient with papillary carcinoma of the kidney developed a selective and massive infarction of the neoplastic tissue after fine needle aspiration biopsy. CONCLUSION: Papillary carcinoma of the kidney should be added to the list of neoplasms prone to undergo ischemic infarction after fine needle aspiration.

Adult↗