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Biomedical subjects

M Moussa

Publications and source records attributed to M Moussa.

At least 37 records · Page 2Linked to original sources

HIV-1 co-receptor expression on trophoblastic cells from early placentas and permissivity to infection by several HIV-1 primary isolates.

We examined CD4 and major HIV-1 co-receptor expression by trophoblast cells (TC) from early placentas, and the permissiveness of TC for infection by several natural HIV-1 isolates in vitro. Ten early placentas (4-6 weeks of gestation) from HIV- women were obtained after elective abortion. CD4 and HIV-1 co-receptor expression by TC was examined in terms of both mRNA and protein. The same TC were then challenged with three clinical HIV isolates of known phenotype, two originating from mothers who transmitted the virus to their child and one from a vertically infected newborn. TC infection was detected by polymerase chain reaction. CD4 expression was detected in five of the 10 placentas, while membrane protein expression of CCR3, CXCR4 and CCR5 was detected in every case, despite quantitative differences among individuals. Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations. TC from seven out of eight placentas were permissive to HIV entry, but no productive viral replication was detected (reverse transcriptase activity in culture supernatants). Interestingly, the addition of chemokine(s) or a CD4-blocking antibody to the cultures failed to inhibit TC virus entry. These data point to marked interindividual variability in HIV co-receptor expression by trophoblast cells and show that TC from early placentas can be infected in vitro by clinical HIV-1 isolates. They also suggest that viral entry in vitro might occur through a mechanism independent of both CD4 and chemokine receptors.

Acquired Immunodeficiency Syndrome↗

High frequency oscillatory ventilation during repair of neonatal congenital diaphragmatic hernia.

We evaluated the use of high frequency oscillatory ventilation (HFOV) during congenital diaphragmatic hernia repair. After preoperative stabilization, 22 newborn infants were ventilated with HFOV during surgery. Ventilatory settings, blood gas values and oxygenation index were recorded before, during and after surgical repair. No differences were noted for these variables. No complications related to ventilation were recorded. According to the surgeon, diaphragmatic repair during HFOV is facilitated. This study confirms that CDH can be safely repaired using HFOV during anaesthesia.

Analysis of Variance↗

In vivo effects of olive oil-based lipid emulsion on lymphocyte activation in rats.

Numerous studies suggest that immune function may be compromised by lipid emulsions rich in polyunsaturated fatty acids, especially linoleic acid. In our study, we compared the effect of a new olive oil-based lipid emulsion (ClinOleic(R)) containing 18% linoleic acid, and an emulsion based on soybean oil (Ivelip(R); 52% linoleic acid) on lymphocyte functions. Weaning Wistar rats (n= 24) were fed for 4 weeks on an oral diet that contained 12% of total energy as lipids from soybean oil. Then they received, during 6 days, a total parenteral nutrition (260 kcal/kg/d) in which 12% of total energy was brought by one of the two lipid emulsions. The fatty acid profile of spleen lymphocyte phospholipids reflected lipid intakes, with a higher content of oleic acid in ClinOleic(R) group and linoleic acid in Ivelip(R) group. A greater proportion of cells expressed the interleukin-2 receptor a-chain (CD25) after administration of ClinOleic(R) when compared to Ivelip(R) (55.43 +/- 3.47 vs 45.48 +/- 3.26%, P<< 0.05). Moreover, the CD25 expression was positively correlated with oleic acid content of spleen lymphocyte phospholipids (r= 0.500, P<< 0.018). These results show that ClinOleic(R) is able to induce, in vivo, a greater proportion of cells expressing CD25, and suggest that oleic acid could have a role in the observed effects.

Animals↗

PSP94 expression after androgen deprivation therapy: a comparative study with prostate specific antigen in benign prostate and prostate cancer.

PURPOSE: To examine the clinical use of PSP94 (prostate secretory protein of 94 amino acids) as an androgen independent marker, we conducted a comparative study of prostate samples including benign tissue and cancers which did and did not have androgen deprivation. MATERIALS AND METHODS: Among 163 radical prostatectomy cases 75 had androgen deprivation before operation, while surgery was performed in the remainder without prior hormone treatment. Considering the pathological up grading following hormone therapy, contiguous sections from radical prostatectomy samples were stained for PSP94 and prostate specific antigen (PSA) by immunohistochemistry, and equivalent tumor foci were evaluated by assessing the intensity and extent of the staining. RESULTS: In untreated benign prostate tissue PSP94 and PSA staining was positive and identical in all sections in the no pretreatment group. However, PSP94 expression in the androgen deprivation group was significantly higher than PSA in intensity (p = 0.0005) and extent (p = 0.034). In untreated cancer cases PSP94 intensity and extent demonstrated strong inverse association with Gleason grade (p <0.0001). In contrast, PSA expression was high in every grade, resulting in no statistical association with tumor grade. In the androgen deprivation group PSA staining was decreased in every grade compared to the no pretreatment group. On the other hand, PSP94 expression was decreased in grade 3 tumor foci but increased in grades 4 and 5 tumor foci compared with samples of the corresponding grade in the no pretreatment group (p = 0.0034). CONCLUSIONS: PSP94 expression in benign prostate persists under androgen deprivation compared to PSA. PSP94 synthesis in high grade tumor appears to be activated in the absence of androgen stimulation, indicating the possible alternative pathways in the regulation of PSP94.

Adenocarcinoma↗

Impact of the 1997 American Diabetes Association criteria on classification of glucose intolerance among Kuwaitis below 50 years of age.

Type 2 (non-insulin-dependent) diabetes is emerging as a leading chronic non-communicable disease among the adult Kuwaiti population. Based on the World Health Organization and similar reports the projected estimates for subjects suffering from type 2 diabetes by the years 2000 and 2010 show a striking tendency to high rates of the disease in our area. We report the prevalence rates of glucose intolerance among a relatively young adult Kuwaiti population below 50 years of age and the effect of implementing the recent 1997 American Diabetes Association diagnostic criteria on the frequency of type 2 diabetes, impaired glucose tolerance and impaired fasting glucose among this group. The overall prevalence rate for the three categories of glucose intolerance reached as high as 15.8% (95% CI, 14.2 to 17.4). Age, though all subjects were below 50 years, parental history of type 2 diabetes, diastolic blood pressure and serum triglycerides were found to be significant associated risk factors for the development of type 2 diabetes. Obesity was an apparent significant factor associated with the three forms of glucose intolerance (p < 0.001). Obesity and physical inactivity were documented in both non-diabetic and more so in diabetic Kuwaiti adults, which should form the basis of any immediate intervention programme. An integrated approach to the prevention of the described critical risk factors associated with type 2 diabetes is highly recommended in Kuwait. Research, focused on genetics of type 2 diabetes in the highly susceptible Kuwaiti population, should be planned.

Adult↗

Vertical transmission of HIV: parameters which might affect infection of placental trophoblasts by HIV-1: a review. Biomed Group on the Study of in Utero Transmission of HIV 1.

PROBLEM: To understand the mechanisms preventing and/or facilitating maternofetal transmission of human immunodeficiency virus (HIV)-1 across the placenta during pregnancy. METHODS OF STUDY: Current experimental data were reviewed. RESULTS AND CONCLUSIONS: The data about the production of cytokines by placental cells and explants, taken together with information indicating selective passage of certain HIV-1 variants across the placental trophoblast, suggest an intricate regulatory network operating at the fetomaternal interface. The data show a differential differentiation of early and late trophoblasts, as far as HIV entry routes are concerned. We believe this explains the relative predominance of the early infection window, as far as in utero infection is concerned. Whether such a differentiation state can be transiently induced on term placental trophoblasts by several differentiation agents, including cytokines, is being investigated. Whatever the results may be, it is obvious that infection of placental cells is an excellent model of passage infection by HIV of/through a mucosal barrier.

Chemokines↗

Diminished CYP2E1 expression and formation of 2-S-glutathionyl acetate, a glutathione conjugate derived from 1,1-dichloroethylene epoxide, in murine lung tumors.

We hypothesized that resistance of lung tumors to the cytotoxic effects of xenobiotics is associated with loss of cytochrome P-450 expression, leading to defective formation of reactive intermediates. To test this hypothesis, we investigated 1,1-dichloroethylene (DCE), a chemical that causes Clara cell damage, in a urethane-induced model of lung tumorigenesis. Lung metabolism of DCE yields 2-S-glutathionyl acetate (conjugate [C]), a glutathione conjugate derived from DCE-epoxide, believed to be the ultimate toxic species. We used immunohistochemistry to investigate CYP2E1 expression in nontumor- and tumor-bearing lung to identify cells capable of generating [C]. CYP2E1 and [C] were colocalized in adjacent tissue sections to determine coincidence between CYP2E1 and [C] in lung cells. CYP2E1 was highly localized to the bronchiolar epithelium of nontumor-bearing lung and in uninvolved tissue of tumor-bearing lung and was concentrated in the Clara cells. In contrast, tumor foci including hyperplasias, adenomas, and carcinomas were deficient in CYP2E1 in both untreated and DCE-treated mice. Immunoreactivity for [C] was also detected in the bronchiolar epithelium in nontumor-bearing lung and uninvolved tissue of tumor-bearing lung of DCE-treated mice and was reduced in hyperplasias, adenomas, or carcinomas. Thus, there was a coincidence between the sites of CYP2E1 expression and [C] formation. Conjugate [C] accumulated only in lung cells in which CYP2E1 was expressed. Histochemical staining for glutathione confirmed its presence in tumor foci. Thus, bioactivation and conjugation of DCE occur in structurally normal tissue from both nontumor- and tumor-bearing lung but was lost in tumor tissue, irrespective of the stage of tumor development.

Adenoma↗

Metallothionein expression in renal cancer.

OBJECTIVES: To assess metallothionein (MT) expression with immunohistochemical localization in human renal cell carcinoma and to determine whether a possible relationship with the histopathologic findings, tumor grade, or pathologic tumor stage is demonstrable, because MT may have a role in carcinogenesis. METHODS: Archival pathologic specimens and medical records were reviewed for 28 patients with renal cell carcinoma. Immunohistochemical localization of MT was performed with a polyclonal-antibody-to-rat-liver MT, an anti-rabbit IgG linking antibody, and an avidin-biotin horseradish peroxidase complex. Correlation was sought between immunohistochemical data (MT staining intensity, extension, and subcellular site) and clinical data (histologic cell type, tumor grade, and pathologic stage). RESULTS: The mean patient age was 61.7 years (range 42 to 86). The predominant histologic cell type was the clear cell variant. Three, sixteen, and nine tumors were pathologically staged as 1, 2, and 3, respectively. There were 1, 13, 10, and 4 tumors with grades 1, 2, 3, and 4, respectively. Among the independent variables, greater immunoreactivity was observed in Stage 2 tumors (P = 0.028). A significant inverse relationship between tumor grade and MT staining intensity was also observed (P = 0.007). CONCLUSIONS: The inverse relationship in renal cell carcinoma between MT immunoreactivity and tumor grade may indicate a role for MT in tumor growth and dedifferentiation. Increased MT immunoreactivity in lower stage tumors may be related to rapid tumor growth during their growth cycle. Further study is required to elucidate the role of MT in renal cell carcinoma oncogenesis and its possible use as a clinical prognostic parameter.

Adult↗

Non-insulin-dependent diabetes in Kuwait: prevalence rates and associated risk factors.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major clinical and public health problem in Kuwait. The objective of the study was to determine prevalence rates of NIDDM among a representative sample of the Kuwaiti adult population aged 20 and older in two out of five governorates and identify the associated risk factors for the disease. A total of 3003 subjects (1105 men and 1898 women) were interviewed and examined by the research team during the period September 1995 to June 1996. A specially designed questionnaire was completed and the physical examination included height, weight and blood pressure measurements. Fasting blood samples were withdrawn, centrifuged immediately and refrigerated. Interpretation of oral glucose tolerance tests were based on the World Health Organisation diagnostic criteria for diabetes mellitus (1985). The denominator used for computing the prevalence was obtained from the 1995 Kuwait census. The overall prevalence of NIDDM in this study was found to be 14.8% (14.7% in men, 14.8% in women). Diabetic subjects presented at a relatively young age, prevalence rate in the age group 20-39 was 5.7% (95% confidence interval, 4.4-7.0) and in the age group 40-59 was 18.3% (95% confidence interval, 16.1-20.6). Obesity was found to be a significant risk factor, P < 0.001. The strong association of family history of NIDDM (adjusted odds ratio = 1.80, P < 0.001) suggests a genetic component. Hypertension was markedly associated with NIDDM and IGT (P < 0.001). With the demographic transition which already started among the Kuwaiti population and if the prevalence of NIDDM remains the same, aging of the population will contribute to even more upward trends in prevalence of abnormal glucose tolerance with its serious impact on morbidity and mortality among the Kuwaiti population. The strong association between hypertension and NIDDM may suggest a common approach to the prevention and control of these two conditions.

Adult↗

The hemodynamic effects of pneumoperitoneum during laparoscopic surgery in healthy infants: assessment by continuous esophageal aortic blood flow echo-Doppler.

UNLABELLED: Cardiovascular changes due to pneumoperitoneum during laparoscopic surgery are established in adult patients, but not known in infants. We investigated the hemodynamic effects of laparoscopy during general anesthesia in 12 ASA physical status I infants by using noninvasive continuous esophageal aortic blood flow (ABF) echo-Doppler monitoring. During the laparoscopic procedure, intraabdominal pressure was maintained automatically at 10 mm Hg by a CO2 insufflator, and minute ventilation was adjusted to avoid hypercapnia. Hemodynamic changes were continuously recorded on soft magnetic support and assessed at three time intervals: t0 (after the initiation of anesthesia), t1 (5 min after peritoneal insufflation), and t2 (5 min after exsufflation). The induction of pneumoperitoneum resulted in a significant decrease in ABF and stroke volume, and in a significant increase in systemic vascular resistance, compared with control values: 67% +/- 9% (P < 0.001), 68% +/- 10% (P < 0.001), and 162% +/- 34% (P < 0.001), respectively. These changes were completely reversed after peritoneal exsufflation. Pneumoperitoneum caused no significant changes in mean arterial pressure or in end-tidal CO2 pressure. These findings demonstrate that laparoscopy is associated with hemodynamic changes without clinically deleterious consequences in healthy infants during a short duration of pneumoperitoneum. IMPLICATIONS: The peritoneal insufflation achieved during laparoscopic surgery is associated with cardiovascular impairments (decrease in cardiac performance and increase in vascular resistance). We found that these changes had no clinically deleterious effects in healthy infants.

Aorta↗

Invasive carcinomas and fibroadenomas of the breast: comparison of microvessel distributions--implications for imaging modalities.

PURPOSE: To compare spatial patterns of blood vessels between invasive breast carcinomas and fibroadenomas to improve the diagnostic specificity of noninvasive vascular magnetic resonance imaging and color Doppler ultrasound. MATERIALS AND METHODS: Nineteen invasive ductal carcinomas and 20 fibroadenomas from 39 patients were stained for factor VIII-related antigen. Vessels smaller than 40 microns were counted in x200 fields defined in peripheral and central areas of the tumor and in normal tissue adjacent to fibroadenomas. Significant differences in vessel density were determined with Student t tests and one-way analyses of variance. Distributions of vessels 40 microns or larger were qualitatively evaluated. RESULTS: There were 9-105 vessels (mean, 31.4 vessels) smaller than 40 microns per x200 peripheral and 4-57 vessels (mean, 20.1 vessels) smaller than 40 microns per x200 central carcinoma field. There was no significant difference in vessel density between the two groups. Peripheral microvessel density was significantly higher (P < .01) than central microvessel density in 15 (79%) of the 19 carcinomas and in three (16%) of 19 fibroadenomas. (A Student t test could not be performed in one case of fibroadenoma; size permitted only one countable field according to the authors' criteria.) The 18 cases with normal tissue had 21-229 vessels (mean, 80.5 vessels) per field; in 16 (89%) of the 18 cases, these vessel counts were significantly higher (P < .01) than those in the fibroadenoma cases. Vessels 40 microns or larger were found mainly in the periphery of carcinomas and were more uniformly distributed in fibroadenomas. CONCLUSION: Evaluation of the spatial distribution of vessels and the ability to resolve vessel sizes may add valuable information to the imaging-based diagnostic work-up of indeterminate solid breast lesions.

Adult↗

A simple outpatient test for proprioception in the anterior cruciate ligament-deficient knee.

Proprioception was quantified in 32 patients who had an arthroscopically documented complete anterior cruciate ligament tear using a simple single-limb standing test. An age-matched control group underwent identical testing. Control subjects demonstrated identical values between their two limbs, with the mean variation being 4.8%. The test group, however, showed significantly higher mean values for the injured compared with the noninjured limb, the mean variation being 43.8%. Patients who have a complete tear of the anterior cruciate ligament may experience a decline in proprioceptive function of their knees. This can be tested clinically using a simple single-limb standing test in an outpatient setting.

Adult↗

Continuous oesophageal aortic blood flow echo-Doppler measurement during general anaesthesia in infants.

PURPOSE: Invasive haemodynamic monitoring during general anaesthesia in infants is usually limited to very high risk operations, such as cardiac surgery. Nevertheless, different surgical procedures and/or anaesthetic techniques justify additional monitoring for children, as for adults. The aim of this preliminary study was to evaluate the feasibility of using a new echo-Doppler device (Dynemo 3000) capable of measuring continuous aortic blood flow during general anaesthesia in infants. METHODS: Aortic blood flow (ABF) was measured with a small oesophageal probe designed for newborns and infants. The aortic flowmeter was connected with satellite devices to visualise the haemodynamic profile which included ABF, pre-ejection period (PEPi), left ventricular ejection time (LVETi), mean arterial pressure, heart rate, stroke volume and systemic vascular resistance. Twelve infants, aged 8-26 mo, undergoing surgery under general anaesthesia were successively included in the evaluation of this device. Isoflurane (1% end-expired concentration) was introduced to maintain anaesthesia after induction with halothane, midazolam, fentanyl and atracurium. RESULTS: Correct positioning of the probe was easily obtained in all cases and the recording quality was excellent, whatever the operative position. Recordings of haemodynamic data showed some myocardial depression from isoflurane: decreased ABF (indexed to body surface area) and lengthened PEP/LVET (2.24 +/- 0.53 L.min-1.m-2 and 0.32 +/- 0.05 respectively, before introduction of isoflurane and 1.71 +/ 0.53 L.min-1.m-2 (P = 0.027) and 0.39 +/- 0.06 (P = 0.007) with isoflurane). CONCLUSION: These preliminary results suggest that this continuous ABF echo-Doppler device may be valuable for peri anaesthetic monitoring in infants.

Anesthesia, General↗

Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.

We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.

Adolescent↗

Frequency of pathogenic and enteroadherent Escherichia coli in patients with inflammatory bowel disease and controls.

AIMS: To determine whether inflammatory bowel disease (IBD) is associated with pathogenic or enteroadherent Escherichia coli. METHODS: A least two stool specimens and one rectal biopsy were taken from 30 patients with IBD and from 20 controls. A large number of E coli-like colonies cultured from each stool sample and biopsy was tested, using DNA probes, for the presence of genes encoding shiga-like toxins, invasiveness, attachment-effacement and the ability to adhere to HEp-2 cells. Similarity among isolates from stool samples and rectal biopsies was determined by random amplified polymorphic DNA (RAPD) analysis. RESULTS: Enterohaemorrhagic and enteroinvasive E coli were not found in samples from either patients or controls. No significant difference in the detection rate of enteroadherent E coli between patients and controls was found. Rectal biopsies from 11 of 28 patients with IBD and 4 of 18 controls contained E coli, which hybridised with probes for detection of genes encoding diffuse adherence to HEp-2 cells, or encoding P-pili (p = 0.2). Enteroadherent E coli isolated from two or three stool specimens from the same patient or control appeared to be identical by RAPD analysis, and are considered to be residents in the colon. Probe positive isolates obtained from stool specimens and corresponding rectal biopsies were always identical on RAPD analysis. CONCLUSIONS: E coli strains possessing adherence factors reside in the large intestine and adhere to the rectal mucosa, irrespective of the presence of colitis.

Adult↗

Insights into the mechanisms of vertical transmission of HIV-1. BIOMED2 Working Group on the in utero transmission of HIV-1.

This paper is a summary of three oral presentations, as well as the ensuing discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three members of the European Biomed group on vertical transmission of HIV (G. Chaouat, F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D. Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the Pasteur Institute, France; Irène Athanassakis, University of Crete, Greece; Eva Maria Fenyö, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such, this paper intends to be neither a review, nor an original article, but rather is an opinion paper discussing the working hypothesis of this network, as well as some of their recent results, which were presented at this meeting. The paper was issued at the request of the organizers of the meeting.

Anti-HIV Agents↗

DNA cytometric proliferative index predicting organ confinement in clinical stage-B prostate cancer.

PURPOSE: To assess nuclear activity by DNA flow cytometry (FCM), Gleason score and serum prostate-specific antigen (PSA) levels in predicting extracapsular tumour involvement in patients with prostate cancer. DESIGN: Retrospective pathologic study. PATIENTS: Forty patients with clinical stage-B prostate cancer who underwent radical prostatectomy. INTERVENTIONS: The relationship between the pathologic state and each of the proliferative index (PI). Gleason score and PSA level was analysed retrospectively with the use of archival specimens. Preoperative serum PSA levels, were measured by the Hybritech assay. Gleason score was determined by 2 of the authors. Tumours were classified as stage B (confined to prostate), C1 (focal capsular penetration) or C2 (involvement of seminal vesicles or capsular perforation). FCM PI measurements were performed on deparaffinized tumour specimens. RESULTS: All 40 specimens were diploid. There were 9 pathologic stage-B, 16 stage-C1 and 15 stage-C2 tumours. The serum PSA level was 20 ng/mL or less for all patients except 2, for whom the levels were 27.8 ng/mL and 45.9 ng/mL, respectively. A Gleason score lower than 7 had a 76.0% sensitivity and 53.5% specificity in predicting organ confinement. In contrast, a PI of 21 or lower had a 84.0% sensitivity and a 73.0% specificity in predicting organ confinement, with a positive predictive value of 84.0%. Of the 17 tumours with both "favourable" features (Gleason score lower than 7 and PI of 21 or lower), only 1 (5.9%) had extracapsular involvement (stage C2). Of the 6 tumours with both "unfavourable" features (Gleason score higher than 7 and PI of 21 or higher) 5 of 6 were stage C2 and 1 was stage C1. CONCLUSION: The single most consistent predictor of organ confinement was PI alone.

Cell Division↗

Metallothionein expression in prostatic carcinoma: correlation with Gleason grade, pathologic stage, DNA content and serum level of prostate-specific antigen.

OBJECTIVE: To determine the expression of metallothionein (MT) in prostatic carcinoma by immunohistochemical staining. Several lines of evidence have indicated that MT may play a role in carcinogenesis and in drug resistance of tumours. DESIGN: Retrospective pathologic study. INTERVENTIONS: Formalin-fixed, paraffin-embedded archival tissues from 39 radical prostatectomies were analysed. All tumour foci were stained by ABC technique using a primary polyclonal rabbit antibody against rat liver MT. The staining intensity for MT was graded on a scale of 0 to 2+, and the histologic grading was done by the scheme of Gleason. OUTCOME MEASURES: Correlation of MT expression with Gleason grade, preoperative serum prostate-specific antigen (PSA) levels, pathologic stage and DNA content, including S-phase fraction (SPF) and proliferative index (PI). RESULTS: Most of the epithelium of normal prostate tissue had patchy, intense MT staining. All the grade II tumours foci showed intense (2+) staining for MT, while all grade IV and V foci were persistently negative. The grade III tumours foci were heterogeneous. The MT-positive foci showed both nuclear and cytoplasmic staining of variable extent. There were 9, 15, 13 and 2 tumours with pathologic stage B, C1, C2 and D1, respectively. The serum PSA levels ranged from 1 to 16 ng/mL. No apparent correlation existed between the MT staining pattern and the pathologic stage or preoperative PSA level. Thirty-four of the tumours were diploid and 5 were tetraploid. There were significantly higher SPF and PI mean values in the MT-stained tumour cells (p < 0.05), suggesting that MT preferentially stains an epithelial subpopulation, possibly the proliferating cell compartment. CONCLUSION: The positive correlation of MT expression with Gleason grade in prostatic adenocarcinoma suggests a possible role for MT in oncogenesis in prostate cancer.

Biomarkers, Tumor↗