DNA aneuploidy, high SPF and specific p53 mutations are independent prognostic factors in colorectale cancer (CRC)

DNA-aneuploidy and high SPF and specific p53 mutations are independent prognostic factors in colorectal cancer (CRC).

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study

Background Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. Patients and methods The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of …

TP53 Mutation in exon 5 and S-Phase Fraction but not Mutations in Ras gene family and DNA-ploidy are Indipendent prognostic indicators in Laryngeal Squamous Cell Carcinoma

Farmacogenomica nei carcinomi colorettali: prospettive nella terapia personalizzata

Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

Background Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. Patients and methods A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. Results During these mutational screening procedures one case presented three mutations classified…

Pharmacogenomics in colorectal carcinomas: Future perspectives in personalized therapy

The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes …

Ductal Lavage: a valid method of risk assessment and of early diagnosis in breast cance

Fattori predittivi di risposta ai citostatici nei tumori del tratto gastrointestinale. In A Zaniboni “ I tumori del tratto gastroenterico” pag 31-37, Masson Editore, Milano, 2004

Basi fisiopatologiche dell'encefalopatia minima del cirrotico

TP53 mutations are not prognostic indipendent indicators in bladder cancer

The prognostic role of TP53 mutations in advanced laryngeal squamous cell carcinoma (LSCC).

A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother's proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband's brother and her two sons. Direct automatic sequen…

Prognostic significance of p16INK4a alterations and 9p21 loss of heterozigosity in locally advanced laryngeal squamous cell carcinoma

The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting as a tumor suppressor. Genetic alterations involving the 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median of follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) has been studied prospectively. Our purpose was to investigate p16 alterations (9p21 allelic loss, hypermethylation and point mutations) and their possible association with clinico-pathological data and flow cytometric variables (DNA-ploidy and S-phase fraction (SPF)…

TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome.

The aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functio…

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

Purpose: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. Methods: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. Results: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P < 0.05) and DNA aneuploid tumors (P < …

RUOLO DI P53 E DEI GENI K-RAS EDH-RAS NELLA TUMORIGENESI DELLE GHIANDOLE SALIVARI

A study of a new germline mutation in BRCA1 gene in two Sicilian families: a founder mutation?

Un caso di leishmaniosi viscerale progressiva mascherata da un quadro di cirrosi epatica

Laser Pressure Catapulting (LPC): Optimization LPC-System and Genotyping of Colorectal Carcinomas

Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by se…

A missense mutation associated to early onset breast cancer in a sicilian woman.

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same …

Usefullness of abdominal ultrasound in celiac disease: diagnosis anf follow-up

Nm-23-H1 expression does not predict clinical survival in colorectal cancer patients

The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by im…

TP53 in exon 5 and s-Phase fraction but not mutations in Ras gen family and DNA-ploidy are indipendent indicators in laryngeal squamous cell carcinoma

Detection and clinical relevance of free-circulating tumor DNA in blood of patients with colorectal cancer

DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: Results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study

BACKGROUND The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were fol…

BRCA1 germline mutations in Sicilian breast and/or ovarian cancer families and their implications for genetic counselling.

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only …

A3 mutational analysis of BRCA1 gene in sicilian patients at rik fpr inherited breast and/or ovarian cancer:experience of reference center for the biomolecular characterization of neoplasms and genetic screening of hereditary tumors

Chronic Urticaria as a presenting symptom of Crohn’s disease.

Clinical presentation of Crohn’s disease (CD) may be variable according to the location and the intensity of the inflammation. Some patients may have atypical symptoms which could delay the diagnosis. We report the first case of chronic urticaria related to a subclinical, complicated CD. Although the pathologic mechanism of this association was unclear in our patient, this case suggests that in patients with unexplained chronic urticaria it is opportune to investigate for a possible CD, even if there are no or few specific symptoms of intestinal inflammatory disease.

TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.

The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutatio…

Detection and clinical relevance of free circulating tumor DNA in blood of patients with gastrointestinal cancer

VEGFR-2, HSP90 and GRP78/BiP expression and HCC recurrence after Liver Transplantation

Introduction Liver transplantation (LT) for hepatocellular carcinoma (HCC) is a satisfactory therapeutic choice in patients with “early HCC” selected according to Milan criteria. However, the risk of HCC recurrence after LT is about 7-20% at five years and molecular markers which can predict recurrence are still lacking. We investigated in HCC samples and LC surrounding tissues the significance of VEGFR-2, HSP90, and GRP78/BiP expression in patients with HCC who underwent LT in a western transplantation center and their possible role as molecular markers of recurrence. Methods 42 patients (35 M, 7 F) with early HCC who underwent LT between 2012 and 2013 were enrolled. The tumor recurrence r…

TP53, H-K-RAS, P16INK4A GENE MOLECULAR ANALYSIS IN SALIVARY GLAND TUMORS

Le basi scientifiche della cancerogenesi: “up-date”

Aberrant methylation within RUNX3 CpG island associated with the nuclear and mitochondrial microsatellite instability in sporadic gastric cancers. Results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

Background: Gastric cancer (GC) development is a multistep process, during which numerous alterations accumulate in nuclear and mitochondrial DNA. A deficiency of repair machinery brings about an accumulation of errors introduced within simple repetitive microsatellite sequences during replication of DNA. Aberrant methylation is related to microsatellite instability (MSI) by the silencing of the hMLH1 gene. The aim of this study is to investigate a possible relationship between the RUNX3 promoter methylation, nuclear microsatellite instability (nMSI) and mitochondrial microsatellite instability (mtMSI), in order to clarify its biological role in GC. Patients and methods: nMSI and mtMSI were…

DNA-Aneuploidy, High SPF and Specific P53 Mutations are Indipendent Prognostic Factors in Colorectal Cancer (CRC)

Affidabilità del Bright liver echopattern nella diagnosi di steatosi in pazienti con ipertransaminasemia criptogenetica

A.Mutational analysis of BRCA1 in sicilian patients at risk for inherited of reference center for the biomolecular characterizaztion of neoplasm and genetic screening of hereditary tumors

RUOLO DI P53 E DEI GENI K-RAS ED H-RAS NELLA TUMORIGENESI DEI CARCINOMI DELLE GHIANDOLE SALIVARI

BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.

PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total…

Detection and clinical relevance of free-circulating tumor DNA in blood of patients with colorectal cancer. Proceeding of ICACT Fifteenth International Congress on Anticancer Treatment February 9th 12th 2004, Paris accepted for oral presentation

TP53 mutations and microsatellite instability are prognostic factors in gastric cancer?

Havep53gene mutations and protein expression a different biological significance in colorectal cancer?*

p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein overexpression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 protei…

P16, p53 altertaions and S phase fraction are predictive of clinical outcome in Laringeal squamous cell carcinoma.

Diagnostica non invasiva delle varici esofagee nei pazienti con cirrosi epatica: dati ecografici vs dati endoscopici

The aim of this study was to identify possible clinical, biochemical or instrumental markers which can predict in a non-invasive manner the presence of EV. One hundred and fifty-eight consecutive liver cirrhotic patients seen at our outpatient clinic were included in this study. The diagnosis of LC was done on liver biopsy findings or based on instru m e n t a l , clinical and serological data. Patients underwent EGE, ultra - sound of the upper abdomen, Doppler of the main splancnic vessels and the main parameters of liver function were tested. Liver cirrhosis was mostly correlated to hepatitis C virus and most patients were class A according to Child. At EGE, EV w e re absent in 41 patient…

TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

ToprospectivelyevaluatetheprognosticsignificanceofTP53,H-,K-,andN-Rasmutations,DNA-ploidyandS-phasefraction(SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed byflow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triplemutations.Intotal,46TP53mutationswereobserved.Themajority(41%)oftheseoccurinexon5(19/46),…