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Biomedical subjects

R M Tomasino

Publications and source records attributed to R M Tomasino.

At least 19 recordsLinked to original sources
PubMed2006

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 with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression.

Adult↗
PubMed2006

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 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.

Carcinoma, Squamous Cell↗
PubMed2005

Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study.

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.

Adenocarcinoma↗
PubMed2002

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<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. CONCLUSIONS: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Adenocarcinoma↗
PubMed2002

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype.

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Adenocarcinoma↗
PubMed2001

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 Meridonale (GDIM) 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 followed up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality. Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC] staging system) and node status. Moreover, DNA aneuploidy was significantly related to high SPF. K-ras-2 mutations were not associated with clinicopathologic variables or flow cytometric indicators. At univariate analysis, advanced TNM stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy, and high SPF proved to be significantly related to quicker tumor relapse and to shorter overall patient survival. With multivariate analysis, DNA aneuploidy, high SPF, and depth of invasion were related to risk of tumor relapse and patient death, whereas diffuse histotype was independently related to patient risk of tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with clinicopathologic staging, might be useful for the identification of GC patients who have different risks for death or relapse of disease.

Adult↗
PubMed2000

Mature teratoma of the uterine corpus with thyroid differentiation.

A case of a clinically silent mature teratoma of the uterine corpus is reported. A 55-year-old woman presented with multiple uterine leiomyomas. The discovery was incidental, because the patient was asymptomatic. Macroscopically, a colloid-hemorrhagic-looking nodule was present. Histologic and immunohistochemical studies showed that this tumor was a small thyroid mass. Key words:,

Calcitonin↗
PubMed2000

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.

Adenocarcinoma↗
PubMed1999

[The use of stereotaxic cytology in the diagnosis of nonpalpable breast lesions. Our experience].

BACKGROUND AND AIMS: The increasingly frequent use of mammography for the early diagnosis of breast cancer and the consequent identification of mammary lesions at a preclinical stage raises the fundamental problem of the differential diagnosis between non-suspected non-palpable lesions (NPL) which can therefore be monitored over time and suspected NPL or definite carcinoma requiring histological confirmation and surgical biopsy. The diagnostic accuracy of mammography alone is not sufficiently high to differentiate benign lesions from malignant or strongly suspected ones. The use of surgical biopsy in the event of suspected NPL could be significantly reduced by the use of stereotaxic cytology which would improve the diagnostic accuracy of mammography. METHODS: The study refers to 72 suspected NPL undergoing surgical biopsy after having performed stereotaxic cytology on a sample taken with a dedicated mammographic device (Mammotest-TRC). RESULTS: The rate of inadequate samples for correct cytological evaluation was 16.1%. Of the 72 NPL undergoing surgical biopsy, 40 (55.5%) were found to be carcinomas and 32 (44.5%) were benign lesions. The sensitivities of mammography alone and cytology alone in identifying infraclinical breast carcinoma were respectively 0.85 and 0.95. If the results of the two methods were evaluated together, the level of sensitivity was 0.98. CONCLUSIONS: The use of stereotaxic cytology enables a marked improvement to be achieved in the diagnostic accuracy of mammography for the identification of suspected NPL to undergo surgical biopsy, notably reducing the cost of biopsy (number of benign lesions for each carcinoma diagnosed) and consequent discomfort for patients.

Aged↗
PubMed1996

Pleomorphic adenoma and adenoid-cystic carcinoma of salivary glands: immunohistochemical assessment of proliferative activity in comparison with flow-cytometric study.

In this study, 32 pleomorphic adenomas (PAs) and seven adenoid cystic carcinomas (ACCs) were analysed for the evaluation of proliferating cell nuclear antigen (PCNA) indices and flow cytometric variables. Our aim was to assess any possible relationship between these parameters and the clinico-pathological variables and to clarify their histogenesis and reasons for their biological differences. The tumours were divided into three groups, mainly epithelial (E), myxoid (M) and chondroid (C); PCNA labelling index (LI) and weighted mean index (WI) and the WI/LI ratio were analysed in the predominant components; a single PCNA index, weighted by the percentage of each component, was also calculated. Only WI/LI was found to be significantly different in the three components, while PCNA single index did not show either significant differences by sex, age, site and size, or any correlation with the S phase fraction. A significant difference was found between PAs and ACCs by site (P < 0.01) and DNA ploidy (P < 0.05); furthermore, all PCNA indices (single index) were significantly lower in PAs than in ACCs.

Adenoma, Pleomorphic↗
PubMed1995

Prognostic significance of cell kinetics in laryngeal squamous cell carcinoma: clinicopathological associations.

A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation to DNA ploidy and clinicopathological features. All of the patients were followed up for a median of 32 months (range, 5-58 months). A weak, but significant, positive correlation was found between M/V and PCNA indices (except the PCNA weighted mean index:labeling index ratio) or these indices and SPF. At univariate analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05) proved to be related significantly to quicker relapse, whereas T4 (P < 0.05), subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01) were related significantly to shorter overall survival. With multivariate analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high SPF was related independently to the risk of death (relative risk, 7.30). Our study has identified SPF, in addition to histological grade, as an important biological indicator in laryngeal carcinomas.

Aged↗
PubMed1995

Flow cytometric DNA analysis and lysosomal cathepsins B and L in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance.

BACKGROUND: The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. METHODS: Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC: Lysosomal cathepsin B and L activity levels were determined biochemically in matched paired sets of tumor tissue and normal mucosa samples. RESULTS: By univariate analysis, lymph node positivity, poor histologic differentiation, DNA aneuploidy, high SPF, and high tumor/mucosa ratio of cathepsin B activity were significantly related to risk of relapse, whereas only DNA aneuploidy and high SPF proved to be significantly related to risk of death. Multivariate analysis showed that high histologic grade and high SPF values (> 15.1%) were independent prognostic factors related to risk of relapse (relative risk [RR] = 3.54; 95% confidence limits [CL] = 1.05-12.0; and RR = 4.22; CL = 1.54-11.6, respectively), whereas only high SPF was related to risk of death (RR = 3.63; CL = 1.17-11.3). CONCLUSIONS: S-phase fraction is an independent predictor of relapse free and overall survival in patients with locally advanced LSCC. On the basis of these findings, SPF should be used in addition to other established prognostic factors to refine the prognostic assessment of these patients further. More studies are needed for a better evaluation of the prognostic significance of DNA ploidy and that of lysosomal cysteine proteinases in these tumors.

Adult↗
PubMed1995

Chick embryo retina development in vitro: the effect of insulin.

In this paper we study the development of chick embryo retina cultured in vitro and the effects exerted by insulin. Retinas were removed from 7-day embryos and cultured in serum- and hormone-free medium for 7 additional days. Under these conditions retinal cells survived and underwent cholinergic differentiation, as previously ascertained by Hausman et al. (Dev. Brain Res., 1991, 59: 31-37). However, a great retardation of development was noted compared to uncultured control, 14-day retina. In fact both wet weight and DNA and protein content increased much slower than in ovo and the tubulin content decreased below even the starting value. In addition, although after 7 days in culture retinal cells were organized in identifiable layers, nevertheless the typical organization equivalent to 14-day in ovo retina was absent. The addition of insulin in the medium markedly increased the wet weight of cultured retinas, their protein content and the level of tubulin pools, particularly that of non-assembled fraction. Nevertheless insulin did not modify DNA synthesis and did not induce the increment of both neuron specific enolase and actin. Morphological observations show that insulin markedly increased the number and the thickening of the fiber layers. These results, together with the facts that retina synthesizes and secretes insulin and possesses specific insulin receptors suggest that insulin can have autocrine or paracrine regulatory functions in retinal development by exerting a general effect on retinal growth and a more specific one on tubulin production.

Animals↗
PubMed1994

Vimentin expression, proliferating cell nuclear antigen and flow cytometric factors. Prognostic role in breast cancer.

A series of 71 patients undergoing surgery for primary breast carcinoma was prospectively studied in order to evaluate the relative weight for four biologic factors (intermediate filament vimentin expression, proliferating cell nuclear antigen [PCNA], flow cytometric DNA ploidy and S-phase fraction) and of several clinicopathologic and biologic features in predicting clinical outcome (disease-free interval). In univariate statistical analysis, positivity of axillary nodes, high number of mitoses, high nuclear grade, high histologic grade, positivity of vimentin, high flow cytometric S-phase fraction (FCM-S) value, high PCNA and high silver-stained nuclear organizer regions scores were significantly related to risk of relapse. In multivariate analysis (Cox's logistic regression) only histologic grade (3) and high FCM-S values (> 10.7) were independently related to risk of relapse, with hazard ratios of 9.84 and 7.98, respectively. The results of our preliminary, prospective study suggest that FCM-S, in addition to morphologic criteria (histologic grade), may be an important biologic indicator in determining breast cancer patients' prognosis.

Analysis of Variance↗
PubMed1994

p53 expression in human renal cell carcinoma: an immunohistochemical study and a literature outline of the cytogenetic characterization.

In this study both the incidence and pattern of p53 over-expression in various histological subtypes of a series of 36 cases of renal cell Grawitz carcinoma, partially studied in a previous paper, were analyzed. This series consisted of these histologic subtypes: clear cell non papillary (18 cases), clear cell papillary (2 cases), granular cell (5 cases), mixed (clear and granular cell) (9 cases) and spindle cell (2 cases). At present, our aim was, firstly, to see which were the best technical conditions for detection of p53 in the available paraffin-embedded tumor specimens, using several antibodies, specific for various epitopes; secondly, to investigate if some relation might exist between this expression and the histological features of these tumors. Twenty-five per cent (9/36 cases) resulted p53 immunoreactive, the highest percentage being represented in the papillary clear and granular cell carcinomas; low expression was detected in 11 cases (30%) and no reactivity in 16 cases (44%). Neither technical or dilution modifications proved to transform these latter results; however, detection was maximal using the CM-1 polyclonal rabbit antiserum. Thus, in RCC, expression of p53, analyzed in the light of the cytogenetic characterization through a literature review, resulted at low frequency. This finding means that mutation of the p53 gene are not frequent in the neoplastic transformation in RCC. Nevertheless, in spite of the small number of cases and of the short follow-up period of this study, detection of p53 positivity in tumors with either high grade and stage or high proliferative activity could suggest that p53 mutations lead to tumors of a more aggressive type.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Importance of early diagnosis in the improvement of prognosis in breast carcinoma: non-palpable lesions. Preliminary results].

There are still marked differences in the current indications for breast screening proposed by the various international school of oncology. Epidemiological data to the effect that breast screening in asymptomatic women aged over 50 reduces the death rate due to breast cancer now appears to be widely accepted, but an analogous finding for women aged between 40-49 has not yet been confirmed. Following a brief analysis of the most important breast screening programmes carried out to date, the Authors report the preliminary results regarding the identification and biopsy of non-palpable breast lesions during the course of a screening programme in 1986 by the Dept. of Cancer Surgery. Of a total of 1128 breast scans in asymptomatic patients aged between 40 and 73, 24 suspect (1.9%) non-palpable lesions were found of which 5 (20.8%) proved to be carcinomas.

Adenofibroma↗
PubMed1990

[The value of the triad: clinical examination, mammography and needle aspiration cytology in the diagnosis of breast carcinoma. Our experience].

Based on the authors' personal experience of the use of the triad, clinical examination, mammography and needle-aspiration cytology, in the strategic diagnosis of breast cancer, the paper emphasizes the importance of early diagnosis as the sole means of obtaining an improved outcome. Using this integrated methodology the authors have obtained a specificity of 99%, sensitivity of 97.8%, and a diagnostic accuracy and prognostic value for positive tests of 98%. In conclusion, the authors affirm that the comparative interpretation of clinical examination, mammography and cytology appears to be an extremely efficacious and reliable method for the diagnosis of the nature of breast nodules.

Adult↗