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D Treré

Publications and source records attributed to D Treré.

12 recordsLinked to original sources

The prognostic value of the AgNOR parameter in human breast cancer depends on the pRb and p53 status.

BACKGROUND: The amount of argyrophilic nucleolar organiser regions (AgNORs) represents a cell kinetics parameter used in tumour pathology for prognostic purposes. AgNOR expression is directly related to the rate of ribosome biogenesis, which has been recently shown to be controlled also by the tumour suppressor proteins pRb and p53. AIMS: To ascertain the relative prognostic value of AgNORs and of pRb and p53 expression in breast carcinoma. METHODS: This study was carried out on 335 human primary breast carcinomas with a median follow up time of 108 months. AgNORs were measured by morphometric analysis on sections that had been selectively silver stained; expression of p53 and phosphorylated and non-phosphorylated pRb forms was assessed by immunohistochemistry. RESULTS: Patients were divided into groups with low (249) and high (86) AgNOR values; with normal (267) and mutated p53 (68); and with normal (256) and hyperphosphorylated or deleted pRb (79). Univariate analysis of disease free survival showed that AgNORs and the status of pRb and p53 were significantly related to the patients' clinical outcome. However, among the four groups characterised by different pRb and p53 status, the AgNOR parameter was not capable of distinguishing subgroups of patients with different clinical outcomes. CONCLUSIONS: These findings indicate that the prognostic value of the AgNOR parameter depends on the status of the tumour suppressor proteins pRb and p53, and it cannot be ascribed to the relation between AgNORs and the cell proliferation rate.

Biomarkers, Tumor↗

Progression on metastatic neuroendocrine carcinoma from a recurrent prolactinoma: a case report.

A 54 year old man was referred to the department of neurosurgery for frontal headache and vomiting. The patient was known in the department because of previous multiple surgery for a locally invasive pituitary prolactinoma (eight years, three years, and one year previously). The neurological examination revealed a frontal mass, which adhered to the dura, suggesting a meningioma. One year later, a left temporal metastasis was removed. Three months later, the patient died, with spinal metastases, of massive lung embolism. Histology revealed a progression of adenohypophyseal prolactinoma on neuroendocrine carcinoma, with an increase in proliferating indexes and modification of hormone production. This study documents a 10 year history of a rare prolactin producing pituitary carcinoma, which metastasised via liquoral flow.

Carcinoma, Neuroendocrine↗

Thymidylate synthase protein expression and activity are related to the cell proliferation rate in human cancer cell lines.

AIMS: To ascertain whether the expression and enzyme activity of thymidylate synthase (TS) are related to the rapidity of cell proliferation in human cancer cell lines. METHODS: Ten asynchronously growing human cancer cell lines of different origin were used, characterised by various doubling times. TS expression was evaluated by western blot analysis using the TS 106 monoclonal antibody. TS activity was determined by the enzyme catalytic assay. The quantitative variation of TS in different phases of the cell cycle was investigated using two parameter flow cytometry for the TS protein and DNA analysis. The number of proliferating cells was evaluated by Ki67 immunostaining. RESULTS: TS expression and activity were significantly related to each other (r = 0.765; p = 0.01) and to the cell doubling time (r = -0.899; p < 0.001 and r = -0.919; p < 0.001, respectively). Ki67 immunolabelling showed no association between the number of cycling cells and TS protein expression and activity. Two parameter flow cytometry indicated that differences of TS expression in the cell lines were not related to the cell cycle phases or to the proportion of S phase cells. CONCLUSIONS: These results show that the expression and activity of the TS protein in asynchronously growing cancer cells are significantly related to the cell doubling time; the faster the cell proliferation, the greater the expression and activity of TS. These findings could explain why TS values are of prognostic value per se and why tumours with high TS expression benefit more from chemotherapy.

Biomarkers, Tumor↗

c-erbB-2 over-expression in amplified and non-amplified breast carcinoma samples.

We investigated c-erbB-2 oncogene amplification and over-expression in 79 invasive breast carcinoma samples using fluorescence in situ hybridization (FISH) and immunohistochemistry, with the aim of studying relationships between neoplasms over-expressing c-erbB-2 with or without amplification and bio-pathological parameters used in clinical breast cancer. Nineteen samples showed amplification, and all of these were positive by immuno-histochemistry. Moderate or intense immunostaining was present in a further 22 samples without c-erbB-2 amplification and was not related to any increased number of c-erbB-2 signals: 15 samples exhibited chromosome 17 polysomy, 3 monosomy and 4 no FISH abnormalities. Thirty-eight samples were immunonegative: 18 exhibited chromosome 17 polysomy, 9 monosomy and 11 no alterations. Samples having c-erbB-2 over-expression associated with amplification showed DNA aneuploidy and hormonal receptor loss to a greater extent than those expressing c-erbB-2 without amplification or immunonegative samples (chi2 test, p = 0.007, 0.008 and 0.008, respectively). The proliferation rate, detected by Ag-NOR staining, was highest in amplified samples (Kruskal Wallis test, p = 0.009). Our results indicate that tumours showing both c-erbB-2 over-expression and amplification exhibit more aggressive biological characteristics than those with only over-expression or immunonegative tumours. Since both c-erbB-2 amplification and over-expression have been related to negative responses to chemotherapy and poor prognosis, these differences might have clinical implications. The combination of FISH and immuno-histochemistry may be helpful to achieve this aim.

Breast Neoplasms↗

Enzymatic cytochemistry, DNA ploidy and AgNOR quantitation in hepatocellular nodules of uncertain malignant potential in liver cirrhosis.

Conventional histological examination of echo-guided biopsy specimens can be inconclusive in small nodular lesions in cirrhotic livers. We investigated the diagnostic potential of cytochemical analysis of dipeptidyl-peptidase IV (DPP IV), of image analysis of nuclear DNA content, and of interphase silver-stained nucleolar organizer regions (AgNORs) in 12 cases of small (13- to 29-mm in diameter) hepatic nodules visualized in cirrhotic patients by ultrasonography. All cases underwent an echo-guided liver biopsy at the time of detection and in none of them were histological signs of malignancy found. Characterization with the above-mentioned techniques was always done at the time of histological examination. These patients underwent a mean (+/- SD) follow-up of 27.0 (+/- 11.2) months after biopsy, with repeated ultrasound (US) examinations. In the seven patients with subsequent neoplastic growth, DPP IV score was altered in five of six; the fraction of mononucleated polyploid cells was altered in six of seven; and the AgNOR quantity exceeded the cutoff value of 4 microns2 in five of five cases. Among the five lesions whose US appearance remained unchanged during the follow-up, only one abnormality (AgNORs) was found in one case. The combined cytochemical analysis of DPP IV, nuclear DNA content, and quantitative evaluation of interphase AgNORs in biopsy samples may contribute to the differential diagnosis of hepatocellular nodules of uncertain type in the cirrhotic liver.

Biopsy↗

Relation between deletion of chromosome 1p36 and DNA ploidy in breast carcinoma: an interphase cytogenetic study.

Aims-To investigate whether deletion of the 1p36 region of chromosome 1 is independent of DNA ploidy in breast cancer cells.Methods-Preparations of nuclei from 64 fresh primary breast tumours were studied using dual target fluorescence in situ hybridisation (FISH) combining probes specific for the 1q12 (pUC 1.77) and 1p36 (1p-79) regions of chromosome 1. Signals were counted in 100-300 nuclei and the percentage of cells showing fewer p1-79 than pUC 1.77 signals was measured in each sample. DNA ploidy was investigated by cytofluorimetry in 55 tumour samples.Results-Chromosome 1 aberrations were detected in 56 samples. There were fewer p1-79 than pUC 1.77 signals in 53 samples. The 1p36 region was deleted in 11 samples in which a single p1-79 signal was detected; seven of these samples were diploid. Abnormalities were found in 17/24 diploid and 30/31 aneuploid tumours.Conclusions-Chromosome 1 aberrations, including deletion of the 1p36 region, were observed in diploid breast tumours. Deletion of the 1p36 region may be an early event in tumorigenesis. Given the frequency and importance of chromosome 1 aberrations in the biological behaviour of breast tumours, FISH, used in conjunction with cytofluorimetry, may be helpful for determining prognosis in patients with diploid tumours.

Journal Article↗

A new marker for early detection and indicator of progression of cancer of the bladder. Preliminary results with Ag-NOR index in 38 cases of superficial bladder cancer.

The multiform biology of superficial bladder tumors, both morphologically and evolutively, and the lack of reliable predictors of progression have led the authors to study the Ag-NOR proteins as a new marker of these tumors. It is well known that particularly the low-grade superficial tumors frequently relapse on the same histologic and proliferative module. Their potential of progression is probably present at the time of the first manifestation of the disease or it can show itself along the relapsing evolution with classic modifications translating the cellular dedifferentiation. The NOR index, set up by the authors, has several advantages: firstly, it corresponds to a functional value of normal and neoplastic cells; secondly, it can be used also with paraffin blocks. Another advantage is the semiautomatic lecture, reproducible also in the urinary cytology, mainly of low-grade tumors, reducing the number of false-negatives. The conclusion of the study of 38 cases of superficial bladder cancer has induced the authors to believe that an increased NOR index is a reliable 'marker' of their progression. Therefore, the authors suggest the use of the NOR activity for the surveillance of the urothelial disease and for a more logical therapeutic strategy.

Adult↗

Nucleolar organizer regions: preliminary results of the clinical use of a new marker for prostatic carcinoma (40 cases).

It is a widely diffused opinion that moving backwards in time the moment of the diagnosis of cancer of prostate, so that the tumor is detected earlier than normal, means that the treatment would be more effective than the one adopted in the usual times of diagnosis. For this reason the earlier diagnosis of prostate cancer has become more and more a compulsory target of the modern urologist, at a time of booming of the third age, of increased lifetime expectancy, of significant elevation of prostate cancer rate and of the persistent uncertainty of the efficacy of available treatments. Theoretically the mortality rate of prostate cancer can be reduced by the prevention programs and by the improvements of treatment methods, but the 'earlier' diagnosis is certainly an easier and less expensive strategy to achieve the same objective. The authors have evaluated the argyrophilic-nucleolar organizer region (Ag-NOR) proteins on 40 cases of adenocarcinoma of prostate collected through a multicentric program in France and in Italy. The Ag-NOR have been stained with silver technique set up by Ploton and Derenzini while the quantitative index has been evaluated by a semiautomatic system partially commercially available, partially modified by the authors. The conclusions: (a) the Ag-NOR index is a simple and reproducible method; (b) the Ag-NOR staging system corresponds to Gleason's grading; (c) the Ag-NOR elevation is a reliable marker of increased cell proliferation and is detectable much earlier than the morphologic changes of Gleason's classification.

Adenocarcinoma↗

The Ag-NOR proteins and transcription and duplication of ribosomal genes in mammalian cell nucleoli.

The relationship between the Ag-NOR (silver-stained Nucleolar Organizer Region) proteins and the functional-structural organization of the nucleolar ribosomal chromatin was studied in regenerating and cortisol-stimulated rat hepatocytes. Statistical analysis of Ag-NOR proteins, carried out with an automated image analyzer, indicated that in regenerating rat hepatocytes the quantity of Ag-NOR proteins mainly increased between the 4th and 12th h of regeneration, reaching a level twice that of resting hepatocytes. Also the synthesis of pre-ribosomal RNA (pre-rRNA) was stimulated after the 4th h of regeneration. Cycloheximide administered to rats at a dose of 0.025 mg/100 g body weight (bw) prevented any increase in Ag-NOR proteins but did not hinder the stimulation of pre-rRNA synthesis. In 8 h cortisol-stimulated hepatocytes no significant change in amount of Ag-NOR protein was observed whereas pre-rRNA synthesis was highly increased as in 12 h regenerating hepatocytes. These results indicated that in rat hepatocytes Ag-NOR proteins and stimulation of pre-rRNA synthesis are not related. The relationship between the Ag-NOR proteins and the distribution of the completely extended intranucleolar ribosomal chromatin was also studied in regenerating rat hepatocytes. At 12 h after partial hepatectomy an increased amount of completely extended ribosomal chromatin was observed, contemporaneously with an increased quantity of Ag-NOR proteins. These ribosomal chromatin changes preceded the beginning of DNA synthesis and were prevented by cycloheximide-induced inhibition of protein synthesis.

Animals↗

Bone hemangioendothelioma: an immunohistochemical study related to histological malignancy and proliferative activity (NORs).

AIMS AND BACKGROUND: Forty-four bone hemangioendotheliomas (HEs) of different histological grades were studied to evaluate the expression and distribution of laminin, type IV collagen, cathepsin G and cathepsin D in cell differentiation and malignancy. RESULTS: In poorly-differentiated HEs the discontinuous distribution of laminin and type IV collagen around angioblastic cords, tubes and cavities revealed an irregular and disorganized basement membrane (BM) architecture corresponding to an increased cell proliferation and secretion of cathepsin D and cathepsin G by tumor cells. CONCLUSIONS: The mean nucleolar organizer region (NOR) area, as a measure of cell proliferation, was significantly higher in grade 4 malignancies than in lower grades, revealing novel prognostic parameters.

Adult↗

Prognostic relevance of silver-stained nucleolar proteins in sarcomatoid carcinomas of the breast.

Fourteen cases of sarcomatoid carcinomas of breast were evaluated by means of a silver technique that selectively stains proteins located in the nucleolar organizer regions (Ag-NORs). The mean area of Ag-NORs (MNORA) was in each case quantitatively analyzed by means of an automated image analyzer. Patients who died early of the disease had a higher MNORA than patients who survived longer than 3 years. The difference was statistically significant. Ag-NORs might be a novel parameter of prognostic relevance in specific cases.

Adult↗