PubMed Health⌕ Search

Biomedical subjects

V Molinie

Publications and source records attributed to V Molinie.

14 recordsLinked to original sources

Detection of telomerase status by semiquantitative and in situ assays, and by real-time reverse transcription-polymerase chain reaction (telomerase reverse transcriptase) assay in bladder carcinomas.

OBJECTIVE: To investigate whether telomerase activity could be used as a diagnostic and/or prognostic marker of bladder carcinoma, by assessing telomerase activity using semiquantitative and in situ methods, and quantifying telomerase reverse transcriptase (hTERT) mRNA expression in a series of bladder carcinomas. MATERIAL AND METHODS: Telomerase activity was detected by the telomeric repeat amplification protocol (TRAP) assay using a telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA) kit on a series of 29 bladder carcinomas and on three normal bladder samples. hTERT mRNA levels were quantified using real-time quantitative reverse transcription (RT)-PCR. For the in situ detection of telomerase activity, the same telomerase PCR ELISA kit was used and applied to frozen-tissue sections only for discordant cases between telomerase activity and hTERT mRNA status. RESULTS: Telomerase activity was positive in 15 of the 29 bladder carcinomas (52%) and negative for the three normal bladder samples. hTERT was detected and quantified in all tumour samples, with major differences in hTERT values. None of the three normal bladder samples had quantifiable hTERT mRNA, giving complete sensitivity and specificity for the method in diagnosing bladder carcinoma. Comparing the results of RT-PCR and TRAP assay showed a significant association between the enzyme activity and levels of hTERT mRNA expression, with only five discordant cases, most of them being TRAP-negative and hTERT-positive. Among these cases the in situ results of telomerase activity were concordant with hTERT mRNA levels by RT-PCR and not with TRAP assay results, as nuclear fluorescence of malignant epithelial cells. The semiquantitative evaluation of positive cell numbers showed a heterogeneity of telomerase activity within the tumour tissue. There was a significant correlation between RT-PCR and histopathological variables (grade and stage), and a significant correlation between TRAP assay results and histopathological grade. CONCLUSION: Detecting hTERT mRNA by RT-PCR seems to be a promising method, with a much better sensitivity than the TRAP assay in diagnosing bladder carcinomas, and a better correlation with histopathological variables. False-negative cases on the TRAP assay are explained by the heterogeneity of telomerase activity within tumour cells. Thus evaluating hTERT gene expression levels could be used as a marker of malignant progression, useful in the early diagnosis and follow-up of bladder carcinomas.

DNA-Binding Proteins↗

Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette-Guerin instillations.

PURPOSE: Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. RESULTS: Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). CONCLUSIONS: Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.

Adjuvants, Immunologic↗

[Indication and strategy for further biopsies following the diagnosis of prostatic intra-epithelial neoplasia].

Prostatic Intraepithelial Neoplasia (PIN) lesions are characterized by proliferation of the epithelial cells lining prostatic ducts and acini. Only high grade PIN lesions (grades 2 and 3) should be reported on biopsy histology reports. The authors present a review of the literature. The clinical importance of demonstration of isolated PIN lesions on prostatic biopsies is based on the high risk of associated invasive cancer present in the prostatic gland in 22% to 100% of cases, usually adjacent to the zone presenting PIN lesions. This risk increases as the grade of the PIN lesion increases, when there is a clinical (abnormal digital rectal examination) or laboratory suspicion (elevation PSA > 10 ng/ml), or in elderly patients. Identification of a high grade PIN does not require any immediate treatment decision. PSA assays do not need to be repeated. A new series of biopsies is recommended after three months. The optimal strategy for the choice of the new biopsy sites has not been defined. In the case of a first series of sextant biopsies, a new series of biopsies is recommended, combining biopsies directed towards the site of PIN lesions (3 biopsies in the site of PIN lesions, 2 biopsies adjacent to this site) and systematized biopsies of the same side. In the case of a first series of non-systematized biopsies, a new series of systematized biopsies is recommended.

Biopsy↗

p53 status does not predict initial clinical response to bacillus Calmette-Guerin intravesical therapy in T1 bladder tumors.

PURPOSE: In superficial urothelial tumors of the bladder, p53 status is currently the most informative pretreatment parameter to define a population at higher risk for invasive carcinoma. Also, in T1 tumors, occurrence of muscular invasion is often related to an early relapse following BCG therapy. With the knowledge of biological parameters able to identify the group of initial BCG therapy non-responders, it would be possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the predictive value of the p53 tumor status on the early BCG therapy response. MATERIALS AND METHODS: The population included a selected group of 43 patients presenting T1 bladder tumors with no carcinoma in situ (Tis), treated by transurethral resection (TUR) followed by intravesical BCG therapy. Clinical outcome was analyzed in relation to usual clinical and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using DO7 monoclonal antibody. For 16 specimens, p53 gene was investigated using a Single Strand Conformation Polymorphism (SSCP) analysis and sequence determination. RESULTS: p53 anomalies were strongly correlated to smoking behavior (p = 0.003) and tumoral grade (p = 0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followup revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of DO7 immunostaining in detection of p53 anomalies. CONCLUSIONS: In T1 bladder tumors, pretreatment p53 determination was not useful to define a group of early BCG non-responders. Thus, p53 status and immunological response induced by BCG endovesical therapy are two independent events.

Adult↗

Primary Epstein-Barr virus-related non-Hodgkin's lymphoma of the pleural cavity following long-standing tuberculous empyema.

Primary non-Hodgkin's lymphomas of the pleural cavity have been described mostly in Japan. We report a case of high-grade non-Hodgkin's lymphoma (immunoblastic type) of the pleural cavity occurring in a nonimmunocompromised patient 55 years after an artificial pneumothorax was performed for the treatment of pulmonary tuberculosis. Immunohistochemical study revealed a B phenotype (CD20), and an in situ hybridization detected small nuclear RNAs encoded by Epstein-Barr virus in most lymphomatous cells. A link between primary pleural lymphoma and the local long-standing chronic inflammation, inducing a clonal transformation of Epstein-Barr virus-infected immortalized B lymphocytes, is suspected.

Aged↗

Cardiac localization of non-Hodgkin's lymphoma: two case reports and review of the literature.

Secondary non-Hodgkin's lymphoma of the heart (SNHLH) are more frequent than primitive non-Hodgkin's lymphoma and represent the third most common malignant tumour of the heart in autopsy studies. Cardiac involvement usually occurs as a late manifestation in patients with disseminated disease. Initial cardiac lymphoma, defined as cardiac involvement at initial diagnosis with concomitant extracardiac localizations, have nevertheless been reported in approximately 42 cases. The present paper concerns two patients with non-Hodgkin's B-cell lymphoma where cardiac involvement occurring 3 and 6 years after initial diagnosis constituted the unique site of relapse. These cases differ from previous reports of the literature by the predominance of extranodal localizations at initial diagnosis and the late onset of cardiac involvement. Clinical and radiological findings were otherwise in accordance with those usually described in such patients. Transthoracic echocardiography revealed the cardiac tumour in the first case, but in the second case transoesophageal echocardiography and magnetic resonance imaging (MRI) were required to demonstrate its presence. As in most reports, the site of tumour involvement was the right cardiac cavity and histology showed high grade B-cell non-Hodgkin's lymphoma. Polychemotherapy, associated with radiotherapy in the second case, led to partial or complete remission of the cardiac tumour without recurrence within the months of follow-up, although both patients died of their disease within one year.

Aged↗

[Paget disease of the vulva. 36 cases].

Thirty six patients with Paget's disease of the vulva were reviewed. The median age of the patients at diagnosis was 67 years (range: 45-91 years). One patient had a history of previous mammary adenocarcinoma. Screening for malignancy revealed two colonic tumours. Two patients with negative screening at presentation developed, 12 and 18 months respectively after vulvectomy, an ovarian carcinoma stage IIc and a cervical and urethral adenocarcinoma. All patients were treated by surgery based on extent of the disease. The operations performed included total vulvectomy (n = 11), partial vulvectomy (n = 14) and wide local excision (n = 4). Out of the 36 patients, 29 were available to follow-up. The median follow-up period was 74 months (range 2-204 months). Three patients died of metastatic disease due to vulval adenocarcinoma and breast carcinoma, or of liver metastases from an unknown adenocarcinoma. Eighteen of the 29 patients followed up remained free of disease. Five out of the 16 patients with positive margins recurred, as did 5 out of 9 patients with negative margins. Treatment of Paget's disease of the vulva is surgical. In order to prevent recurrence, some authors have proposed surgical excision extending beyond the visible clinical lesions with intraoperative frozen sections. The data we recorded show that free margins do not seem to correlate with recurrence, so that large excision beyond the clinical lesion is not useful.

Aged↗

Altered gap and tight junctions in human thyroid oncocytic tumors: a study of 8 cases by freeze-fracture.

Human oncocytic tumors of the thyroid gland may be either adenomas or carcinomas. The morphology and the ultrastructure of these oncocytes are well-known. Numerous studies have demonstrated the role of gap and tight junctions in experimental and human carcinogenesis; however, the junctional complexes of the oncocytic tumors have never been studied. The aim of this study is to analyze gap and tight junctions in the oncocytic tumors of the thyroid. Because they are morphologically similar, whether benign or malignant, they offer an attractive model for studying the junctional complexes in both benign and malignant lesions. Eight oncocytic human thyroid tumors were collected and studied by freeze-fracture. Four of these cases were benign and four were malignant. Four cases of normal gland were also studied to represent the control group. Normal tight and gap junctions were described for the control group. No gap junctions could be found for the oncocytic tumors. Furthermore, alterations of the tight junctions were described; especially focal tights in the oncocytic adenomas and well organized and labyrinthic tight junctions in the oncocytic carcinomas. The lack of gap junction in the benign as well as in the malignant oncocytomas may suggest that the absence of gap junction is not sufficient for malignancy. The alterations of the tight junctions found in the oncocytic tumors of the thyroid are similar to those observed in poorly differentiated tissues or tumors, and may suggest a cellular regression rather than a tumorogenic factor.

Adenoma, Oxyphilic↗