P. Teillac

Predisposing Gene for Early-Onset Prostate Cancer, Localized on Chromosome 1q42.2-43

There is genetic predisposition associated with >=10% of all cancer of the prostate (CaP). By means of a genomewide search on a selection of 47 French and German families, parametric and nonparametric linkage (NPL) analysis allowed identification of a locus, on chromosome 1q42.2-43, carrying a putative predisposing gene for CaP (PCaP). The primary localization was confirmed with several markers, by use of three different genetic models. We obtained a maximum two-point LOD score of 2.7 with marker D1S2785. Multipoint parametric and NPL analysis yielded maximum HLOD and NPL scores of 2.2 and 3.1, respectively, with an associated P value of . 001. Homogeneity analysis with multipoint LOD scores gave an estimate of the proportion of families with linkage to this locus of 50%, with a likelihood ratio of 157/1 in favor of heterogeneity. Furthermore, the 9/47 families with early-onset CaP at age <60 years gave multipoint LOD and NPL scores of 3.31 and 3.32, respectively, with P = .001.

An Original Antireflux Ureteroileal Implantation Technique: Long-Term Followup

An original ureteroileal reimplantation technique in which the ureter is placed in a sulcus created in the ileal mucosa was performed on 51 patients (97 ureters). Followup ranged from 3 to 8 years. As determined by excretory urography, retrograde ileography and urine bacteriology studies the method was effective in 85 per cent of the patients, with a low rate of stenosis (1.5 per cent). The use of this technique, initially limited to patients with the U-shaped continent ileal bladder, has been broadened to include those who undergo various reconstructive or urinary diversion procedures that require ureteroileal reimplantation.

Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma

PURPOSE Approximately 50% of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. MATERIALS AND METHODS The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. RESULTS Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. CONCLUSIONS Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

Assessment of microsatellite instability in urine in the detection of transitional-cell carcinoma of the bladder

Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder‐cancer tumors. We have studied, in a blinded fashion, using PCR‐based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional‐cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional‐cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donors renal and urothelial cells (positive controls). No control patients had any evidence of transitional‐cell carcinoma by cystoscopy. Our results provide objective evidence that non‐invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non‐invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC. Int. J. Cancer (Pred. Oncol.) 79:629–633, 1998.

Laser Induced Autofluorescence Diagnosis of Bladder Tumors: Dependence on the Excitation Wavelength

PURPOSE We assessed the ability of laser induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. MATERIALS AND METHODS Three different pulsed laser excitation wavelengths were used successively: 308 nm. (xenium chloride excimer laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1 mm. core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Device performance was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. RESULTS At 337 and 480 nm. excitation wavelengths the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308 nm. excitation wavelength the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. CONCLUSIONS This spectroscopic study could be particularly useful to design a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives.

Genetic predisposition accounts for ≥10% of all cancer of the prostate (CaP) and is therefore considered a major risk factor, together with age and ethnic origin. Several epidemiological studies have suggested that familial clustering of CaP may be associated with an increased frequency of breast and other cancers among relatives. In order to correlate the incidence of CaP with prevalence of breast and other cancers, we have performed uni‐ and multi‐variate analyses on 691 complete pedigrees including probands, who were consecutive patients with confirmed CaP treated in three French urological departments. We have shown a significantly higher risk (RR = 2.3, p = 0.01) to develop breast cancer in families with multiple than in those with a single CaP. Risk of observing other types of cancer within these families was not significant. We then calculated the breast cancer risk in early onset prostate cancer families, and observed a relative risk that is even more significant (RR = 5.5, p = 0.002). Furthermore, the risk was >30 times that a probands mother have breast cancer if CaP occurred below 55 years of age, rather than after 75 years (p = 0.003). This study has therefore shown for the first time, the relatively high penetrance for breast cancer in relatives of early onset CaP patients. Int. J. Cancer 86:883–887, 2000.

Telomerase activity as a potential marker in preneoplastic bladder lesions

Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis.

Radioimmunodetection of lymph node invasion in prostatic cancer. The use of iodine 123 (123I)-labeled monoclonal anti-prostatic acid phosphatase (PAP) 227 A F(ab′l)2 antibody fragments in vivo

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti‐prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 jug of monoclonal antibody 227 A in the form of F(ab′)2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1,3,6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.

Magnetic resonance imaging in patients with penile carcinoma

The aim of the study was to determine the role of pre-operative magnetic resonance imaging (MRI), with and without contrast enhancement, in patients with penile carcinoma. Nine patients with a penile cancer were studied. The staging of the tumours was performed by clinical examination, MRI and surgery, according to the TNM classification. Six patients had primary tumours, of clinical stage T1 (n = 1) and T2 (n = 5). Three other patients had been previously treated and presented with a local recurrence of clinical stage T2. Surface-coil MRI was performed at 0.5 T with T1 weighted sequences before and after gadolinium-DOTA, and T2 weighted sequences. MRI results were compared with the clinical and surgical findings. T1 weighted sequences did not clearly demonstrate the margins of the tumours. T2 weighted sequences were the more useful in five patients, whereas contrast enhanced T1 weighted sequences allowed better delineation of the lesions in only three patients. Therefore, an imaging protocol should include spin echo T2 weighted sequences. Clinical examination correctly staged six of nine tumours; MRI, seven of nine tumours and the combination of both examinations, eight of nine tumours. MRI provided good evaluation of tumoral invasion into the penile shaft.

Noninvasive detection of genetic instability in cells from prostatic secretion as a marker of prostate cancer.

We present a clinical and molecular study of a series of specific loss of heterozygosity (LOH) indicators which, together with PSA, increase the predictability of cancer in early prostate cancer patients. Considering a positive biopsy as the standard reference, the testing parameters for LOH testing are better than the PSA F/T ratio (<25%), suggesting that this noninvasive approach to detecting early prostate cancer could be very useful as a new tool to optimize the indications for iterative prostate biopsies.