Clinical consequences of MRI activity in treated multiple sclerosis.

BACKGROUND: Inflammation on brain MRI is the most sensitive marker of disease activity in multiple sclerosis (MS) but its clinical consequences remain controversial. OBJECTIVE: Here we investigated the clinical consequences of MRI activity in MS subjects treated with two different first line disease modifying agents. METHODS: Seventy-five treatment-naïve subjects with relapsing-remitting MS (N = 61) or clinically isolated syndromes at risk of MS (N = 14) from the BECOME study that had been randomized to interferon beta-1b (N = 39) or glatiramer acetate (N = 36) and followed for up to two years by monthly brain MRI optimized to detect inflammatory activity were studied for the clinical consequences of lack of MRI remission. RESULTS: MRI remission occurred in 46.4% of participants transiently and in 23.2% completely while it was never achieved in 30.4%. There was no difference by treatment in MRI remission, progression of physical disability, or cognitive function. The percentage of relapse-free subjects was 87.5% for the group in complete MRI remission, 47.6% in the group never in remission and 59.4% in the group in transient remission (p = 0.017). Similar differences were observed for six-month-confirmed worsening of ambulatory function as measured by the timed 25 foot walk (p = 0.026) and by Expanded Disability Status Scale (EDSS) (p = 0.10). Cognitive function was lowest at baseline for the group that never reached MRI remission on treatment; this group improved the least upon repeated cognitive testing during the two years of treatment (p < 0.001). CONCLUSIONS: Lack of MRI remission during treatment with interferon beta-1b or glatiramer acetate is associated with higher relapse rate and worsening of physical and cognitive function.

Serum levels of CXCL13 are elevated in active multiple sclerosis.

There is increasing recognition of the important role that B cells play in the pathogenesis of multiple sclerosis (MS). Recently it was reported that the B cell chemokine CXCL13 is elevated in MS serum and cerebrospinal fluid. Here we study whether serum levels of CXCL13 are associated with active MS. We measured serum levels of CXCL13 by enzyme-linked immunosorbent assay in 74 patients with relapsing MS randomized to interferon beta 1b or glatiramer acetate and examined with monthly 3 T brain MRI scans optimized for detection of gadolinium-enhancement for up to 2 years. The median (range) serum levels of CXCL13 pre-treatment were 40 (3-171) pg/ml. Serum levels of CXCL13 were significantly higher at times of active brain MRI scans (p < 0.01). Furthermore, serum levels were higher in patients who never reached MRI remission compared with those in complete (p < 0.01) or partial (p = 0.01) remission. There was a significant positive correlation between the pattern of serum levels of CXCL13 and MRI activity during the first (r = 0.33, p < 0.05) and the full 2 years (r = 0.35, p < 0.01) of the study. Treatment with interferon beta 1b or glatiramer acetate did not affect serum CXCL13. We conclude that the serum levels of the B cell chemokine CXCL13 are associated with active MS.

Association of pathologic diagnoses with clinical findings in chronic endometritis.

OBJECTIVE: To investigate the association of chronic endometritis (CE) with abnormal uterine bleeding, chronic pelvic pain, human immunodeficiency virus (HIV) infection, genital tract infection and salpingitis. STUDY DESIGN: In this retrospective study, specimens obtained from endometrial biopsy, dilatation and curettage or hysterectomy were identified. A total of 123 patients with CE and 177 without CE who were used as controls were included in the study. RESULTS: The patients with CE were younger than controls (p = 0.0001) and were more likely to be premenopausal (p = 0.0004). There was no association of CE with body mass index (p = 0.82), pelvic pain (p = 0.88) or abnormal uterine bleeding (p = 0.80). None of the specimens with CE had atrophic endometrium (p = 0.0018). CE was significantly associated with history of genital tract infection (p = 0.0032), HIV infection (p = 0.0018) and salpingitis (p = 0.0007). CONCLUSION: There was significant association of CE with historical factors, but not with symptomatology.

Does the presence of vaginitis on a Pap smear correlate with clinical symptoms in the patient?

OBJECTIVE: To investigate the association of the finding of trichomoniasis, candidiasis or bacterial vaginosis (BV) on Pap smear with possible symptoms, findings on the clinical examination or treatment that the patient received shortly before or shortly after the results of the Pap smear. STUDY DESIGN: Cases were selected from the Department of Pathology, UMDNJ-University Hospital, Newark. Retrospective chart review of patients who had a diagnosis of Trichomonas or Candida infection or bacterial vaginosis on Pap smear was performed. Controls were patients with none of these organisms on Pap smear. RESULTS: We reviewed 761 charts. Of the patients represented, 78 were menopausal, 258 were pregnant and 425 were neither menopausal nor pregnant; 533 (70%) of the patients had an organism associated with vaginitis on their Pap smear. There was a significant association (p <0.001) between a positive Pap smear finding and signs, symptoms or treatment for vaginitis overall. By individual organism, there was a significant association between a positive Pap smear and clinical indicators of Candida and Trichomonas, but not of BV. CONCLUSION: Finding Candida or Trichomonas organisms on a Pap smear is a reliable indicator of vaginitis associated with these organisms. Finding organisms consistent with a shift in vaginal flora (BV) on Pap smear did not correlate with clinical indicators of vaginitis.

Duration of lactation is associated with lower prevalence of the metabolic syndrome in midlife--SWAN, the study of women's health across the nation.

OBJECTIVE: The objective of the study was to evaluate whether lactation duration is associated with lower prevalence of metabolic syndrome (MetSyn) in midlife, parous women. STUDY DESIGN: This was a cross-sectional cohort analysis of 2516 parous, midlife women using multivariable logistic regression to determine the independent association of lactation and lactation duration on prevalence of MetSyn. RESULTS: One thousand six hundred twenty women (64.4%) reported a history of breast-feeding, with average lifetime duration of lactation of 1.16 (+/- 1.04) years. MetSyn was present in 536 women (21.3%). Adjusting for age, smoking history, parity, ethnicity, socioeconomic status, study site, physical activity, caloric intake, and high school body mass index, women with prior lactation had significantly lower odds of MetSyn (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.63 to 0.99). Furthermore, increasing duration of lactation was similarly associated with lower odds of MetSyn (OR 0.88, 95% CI 0.77 to 0.99). CONCLUSION: Duration of lactation is associated with lower prevalence of MetSyn in a dose-response manner in midlife, parous women.

Characteristics of the urinary luteinizing hormone surge in young ovulatory women.

OBJECTIVE: To define characteristics of the luteinizing hormone (LH) surge in urine. DESIGN: Observational study. SETTING: Academic center. PATIENT(S): 46 women aged 20 to 35 years with regular menstrual cycles. INTERVENTION(S): Collected first morning urine daily, throughout one menstrual cycle. MAIN OUTCOME MEASURE(S): Urinary LH, follicle-stimulating hormone (FSH), estrone conjugate (E1C), and pregnanediol-3-glucuronide (PDG). RESULT(S): Three women lacked LH surges. Mean LH surge: start = day 14.5 (+/-3.6 SD) (range: 9-26); peak = 41.2 mIU/mg creatinine (+/-20 SD) (range: 12.1-104.0); fold increase = 7.7 (+/-3.0 SD) (range: 2.5-14.8); duration = 7.6 days (+/-1.5 SD) (range: 5-11). The onset of LH surge was of two types: rapid onset (within 1 day) (42.9%) or gradual onset (2 to 6 days) (57.1%). Configurations of LH surges were of three types: spike (41.9%), biphasic (44.2%), or plateau (13.9%). All LH surges demonstrated a gradual decrease to baseline. Three women (7%) did not have FSH rises coincident with LH surges. All displayed E1C rises during the middle to late follicular phase. CONCLUSION(S): The LH surges that result in ovulation are extremely variable in configuration, amplitude, and duration. The FSH rise does not seem essential for ovulation. However, an E1C rise occurred in all cycles, confirming the critical role of estrogen in induction of the LH surge.

Is the presence of Trichomonas on a Pap smear associated with an increased incidence of bacterial vaginosis?

OBJECTIVE: Bacterial vaginosis (BV) is associated with significant morbidity. Bacterial vaginosis is due to an overgrowth of anaerobic organisms in the vagina. It has been postulated that the presence of Trichomonas creates an anaerobic environment that favors BV. Thus, BV should be more frequent in the presence of Trichomonas if Trichomonas is creating a favorable anaerobic environment. MATERIALS AND METHODS: A retrospective review of Pap test reports was performed for a diagnosis of coccobacilli consistent with shift in vaginal flora, that is, the presence of clue cells. Cases were Pap smears with Trichomonas identified. Controls were cases without Trichomonas. Results were analyzed using Fisher exact test. RESULTS: Four hundred cases were reviewed; 200 with and 200 without Trichomonas. The incidence of BV was significantly higher in the Trichomonas group (46.5%) than in group without Trichomonas (24.5%) (p < .0001.). CONCLUSION: The presence of Trichomonas on a Pap smear is associated with an increased incidence of BV. The report of Trichomonas on a Pap smear should prompt clinical consideration that BV may be present.

Ethnic differences in past hysterectomy for benign conditions.

BACKGROUND: Hysterectomy for a benign condition is common, particularly in the underserved. The objective was to determine if ethnic differences could be explained by known risk factors. METHODS: A phone survey was conducted at random on 15,160 women, ages 40-55, from seven US cities. Subjects were 49.9% Caucasian, 28.1% African American, 12.3% Hispanic, and 9.8% Asian American. RESULTS: Ethnicity was associated with past hysterectomy (odds ratio [OR]: Caucasian = 1.0, African American = 1.66; confidence interval [CI] = 1.46-1.88, Hispanic = 1.64, CI = 1.29-2.07; Asian American = 0.44, CI = 0.34-0.56), after adjustment for age, education, fibroids, body mass index, marital status, smoking, geographic site, and country of education. CONCLUSION: Because the highest rates occurred in the disadvantaged African American and Hispanic subgroups, and could not be explained by known risk factors, disparity in the form of overuse in these disadvantaged groups may exist.

Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.

Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.

Menopause and hypothalamic-pituitary sensitivity to estrogen.

CONTEXT: The onset of human menopause is thought to be caused solely by ovarian failure and oocyte depletion. However, clinical symptoms and certain recent data in perimenopausal women suggest central nervous system involvement. OBJECTIVE: To determine if modifications of hypothalamic-pituitary response to estrogen feedback mechanisms occur in older reproductive-age women as a mechanism of the onset of menopause. DESIGN, SETTING, AND PARTICIPANTS: The Study of Women's Health Across the Nation (SWAN) is a multiethnic observational cohort study of the menopausal transition in 3302 women at 7 US sites. Of the subcohort of 840 women who participated in the Daily Hormone Study between 1997 and 1999, 680 women had evidence of luteal activity. The remaining 160 women (19%) did not have luteal activity and are the subject of this report. MAIN OUTCOME MEASURES: Daily urinary hormone levels of estrogen and progesterone metabolites, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). RESULTS: Three groups of women were studied: those with estrogen increases with an LH surge, those with estrogen increases without an LH surge, and those with neither. There were no differences in age or ethnicity among the 3 groups of women. Women in the third group (no increases) experienced more menopausal symptoms (hot flashes) than did women in the other groups with estrogen increases. In older reproductive-age women, the frequent existence of anovulatory cycles with estrogen peaks, equivalent to those that result in LH surges in younger women, yet in which no LH surges occur, indicates failure of estrogen-positive feedback on LH secretion. In other anovulatory cycles, follicular-phase estrogen levels did not lower LH secretion as occurs in cycles of younger women, indicating decreased estrogen-negative feedback on LH secretion. CONCLUSION: Our findings are compatible with hypothalamic-pituitary insensitivity to estrogen in aging perimenopausal women.

Potassium chloride supplementation diminishes platelet reactivity in humans.

The prevalence of occlusive stroke is inversely correlated with potassium intake. We explored the hypothesis that a high potassium intake attenuates platelet reactivity, as expressed in ADP-evoked platelet aggregation. We studied healthy men (n=31) and women (n=42), blacks (n=33) and whites (n=40). In this cohort, we supplemented the habitual intake of 17 men and 21 women with 60 mmol KCl/70 kg body weight per day for 3 days and maintained 14 men and 21 women on their habitual intake. We then compared the change in ADP concentration causing 50% of the maximal initial rate (EC50) of platelet aggregation in the potassium-supplemented versus control groups. Potassium supplementation attenuated platelet reactivity, expressed by an increase in EC50 of platelet aggregation (P=0.0005), which was primarily attributable to an increase in EC50 in whites (P=0.0004). Urinary potassium excretion was significantly lower in blacks than in whites under basal conditions and after potassium supplementation. We conclude that potassium supplementation diminishes platelet reactivity, a phenomenon that provides a link between platelet biology and occlusive stroke.

Relaxin regulation of endometrial structure and function in the rhesus monkey.

Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor alpha, but not beta, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.

Mesenteric lymph from burned rats induces endothelial cell injury and activates neutrophils.

OBJECTIVE: Our previous studies indicated that mesenteric lymph duct ligation prevented burn-induced lung injury. Thus, the goal of the present study was to begin to investigate potential mechanisms of this protective effect. DESIGN: Prospective animal study with concurrent control. SETTING: Small animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Mesenteric lymph and portal vein plasma were collected from male rats subjected to a 40% third-degree scald burn or sham burn. The biological effects of these lymph and plasma samples were tested for their ability to kill human umbilical vein endothelial cells (HUVECs), increase HUVEC monolayer permeability, and activate polymorphonuclear leukocytes (PMNs), as reflected in CD11b adhesion molecule expression and superoxide production. Additionally, ileal specimens were harvested at the end of the experiment (6 hrs postburn) for histologic analysis. MEASUREMENTS AND MAIN RESULTS: Postburn mesenteric lymph produced during the first 2 hrs after burn injury and tested at a 5% concentration, but not sham-burn lymph or portal plasma from burned rats, was toxic for HUVECs resulting in cell death after an 18-hr incubation period. Similarly, only postburn lymph increased HUVEC monolayer permeability. Postburn lymph activated both rat and human PMNs as reflected in increased CD11b expression and augmentation of the phorbol myristate acetate-induced superoxide response. Neither sham-burn lymph nor postburn portal vein plasma activated PMNs. Both the burn and sham-burn lymph samples were sterile, indicating that the effects of burn lymph on the HUVECs or PMNs were not due to translocating bacteria. Last, an association was found between burn-induced gut injury and the production of toxic burn lymph. CONCLUSIONS: Burn-induced gut injury results in the production of biologically active factors that are carried in the mesenteric lymph, but not the portal plasma, which injure endothelial cells and activate PMNs and thus could contribute to distant organ injury.

Preservation of myocardial microcirculation during mechanical reperfusion for myocardial ischemia with either abciximab or eptifibatide.

Myocardial Blush Grade (MBG) is an angiographic method of assessing myocardial microcirculation and provides independent risk stratification among patients with normal TIMI 3 flow. Although the beneficial effect of abciximab on microvascular perfusion is well established, the efficacy of eptifibatide in the prevention of platelet aggregation and distal microembolization is less proven. After a pharmacologic shift by our institution towards the use of eptifibatide in patients with unstable angina presenting for PCI, we sought to evaluate our experience by retrospectively comparing the effect on myocardial perfusion between abciximab and eptifibatide following PCI in stable angina or acute coronary syndrome. Microcirculatory perfusion was reviewed in 101 consecutive patients (23 stable angina, 61 unstable angina, 17 non-q MI) undergoing PTCA/stenting. This comparison was between the last group of 51 patients who routinely received standard bolus and infusion of abciximab and the first group of 50 patients who began receiving standard bolus and infusion of eptifibatide. Baseline characteristics between the two groups were balanced, except for more patients with previous CABG in the eptifibatide group. Angiograms were evaluated by 2 blinded independent reviewers for MBG as follows: 0, no blush; 1, minimal blush; 2, moderate blush; and 3, normal blush. TIMI 3 flow was seen in 98 patients. MBG scores were not significantly different in the abciximab group (67% MBG 3; 31% MBG 2; 2.0% MBG 0 1) than in the eptifibatide group (58% MBG 3; 36% MBG 2; 6.0% MBG 0 1); p = 0.34. Patients with prior PTCA/stenting had lower MBG scores (0 2) compared to patients without prior PTCA (58% vs 31%; p = 0.03). There were significantly lower MBG scores in all patients with prior PTCA or CABG compared to patients without (55% vs 30%; p = 0.03). MBG scores significantly and inversely correlated with peak troponin I levels (r = -0.18, one-tailed p = 0.04). The similarity in myocardial perfusion between abciximab and eptifibatide suggests that both compounds are equally effective in reducing platelet aggregation and microembolization during mechanical reperfusion. Lower MBG scores in patients with prior PTCA or revascularization may be explained by irreversible microvascular dysfunction resulting from distal microembolization during the previous procedure. Lower MBG scores in patients with higher troponin I levels may reflect more frequent microemboli and microinfarcts during an ischemic event. Larger prospective studies need to be performed to validate these findings.

Demonstration of her-2 protein in cervical carcinomas.

OBJECTIVE.: Recently, an immunohistochemical test for her-2-neu has been approved by the Food and Drug Administration for evaluation of breast cancer patients who might benefit from treatment with Herceptin (HercepTest). This study was undertaken to evaluate the immunohistochemical staining patterns in cervical cancer and correlate with clinical parameters. MATERIALS AND METHODS.: A total of 24 cases of invasive squamous cell carcinoma of the cervix were evaluated. Cases were stained using the HercepTest kit according to protocol. Results were graded from 0 to 3+, using the standards set for breast lesions. RESULTS.: A total of 17 cases (70.8%) were negative, 3 cases (12.5%) showed 1+ staining, and 4 cases (16.7%) showed 2+ staining. No cases showed 3+ staining. Higher her-2 staining grade correlated strongly with vaginal margin status. A weak positive correlation was seen between her-2 staining and tumor stage. There was no correlation with tumor grade or histological lymph node status. CONCLUSIONS.: A subset of invasive squamous cell carcinomas of the cervix overexpress her-2 protein. Further studies are needed to correlate with clinical outcome and determine if overexpression of her-2 protein is a marker of cervical carcinoma aggressiveness.

Risk factors for hepatitis C infection among sexually transmitted disease-infected, inner city obstetric patients.

OBJECTIVE: To test the hypothesis that our inner city obstetric patients who have been infected with sexually transmitted diseases (STDs) will have a higher prevalence of hepatitis C virus infection than the general population and to identify specific risk factors and high-risk groups. METHODS: All patients in our prenatal clinic (July 1997-April 1999) who tested positive for one or more STDs were asked to return for hepatitis C antibody testing. Medical charts of all patients who returned for hepatitis C testing were reviewed. RESULTS: A total of 106 patients with STDs were tested for hepatitis C. Positive screening tests for anti-hepatitis C antibody were found in 6.6% (7/106) of the patients (95% CI = 2.7-13.1%). This frequency is significantly higher than the hepatitis C prevalence (1.8%) in the general United States population (p = 0.006). Multiple logistic regression analysis confirmed only older age (p = 0.0 16) and positive HIV status (p = 0.023) to be significant predictors of hepatitis C infection. CONCLUSIONS: Inner city STD-infected obstetric patients are at high risk for hepatitis C infection compared with the general population. Increasing age and HIV-positive status are risk factors which are significantly associated with hepatitis C infection.

Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.

OBJECTIVE: To document prevalence of mild, moderate, and severe urinary incontinence among ethnically diverse perimenopausal women, identify risk factors, and assess the effect of severity on women's daily lives using treatment seeking, bother, and nighttime voiding as indicators. METHODS: Baseline data from the longitudinal cohort of the Study of Women's Health Across the Nation, a prospective, multiethnic, multisite study of the natural history of menopausal transition was used (n = 3302). Interview and self-completed questionnaires assessed most variables of interest. Body mass index and diabetes mellitus were measured clinically. Incontinence severity was derived by multiplying frequency by volume leaked. Risk factors and effect on treatment seeking, bother, and nighttime voiding were assessed by the construction of multiple logistic regression models for each ethnic group and the total population. RESULTS: Mean age was 46.4 years. Incontinence prevalence was 57%, with nearly 15% categorized as moderate and 10% as severe. Biologic factors constituted the most important risk for severity, specifically perimenopausal compared with premenepausal status (odds ratio [OR] 1.35), body mass index (OR 1.04), diabetes mellitus (OR 1.55), and current smoking (OR 1.38). Nonwhite groups had lower risk, but the relationship of ethnicity is complex. Severity was associated with likelihood of discussing with a health care provider, with bothersomeness, and with likelihood of nighttime voiding. CONCLUSION: Large numbers of perimenopausal women experience urinary incontinence with 25% wearing protection or changing undergarments on several days per week. Mutable factors predicting severity included body mass index and current smoking.

Loss of chromosome 16 from renal epithelial cells in humans.

This work explores the notion that low-frequency, acquired aneuploidy may play a role in complex genetic traits such as essential hypertension. To this end, renal epithelial cells in urinary sediments and in renal cysts were examined by fluorescent in situ hybridization with DNA probes specific for the heterochromatic and centromere regions of chromosomes 16 and 1. Chromosome 16 was probed because it harbors variant genes causing monogenic hypertension. These genes have also been investigated for their role in essential hypertension. Chromosome 1 was also probed as an internal control. Higher proportions of renal epithelial cells in the urinary sediments showed monosomy of chromosome 16 than monosomy of chromosome 1 (P<0.001). We also observed in epithelial cells of renal cysts a preponderance of monosomy for chromosome 16 over monosomy for chromosome 1 (P<0.024). Low-frequency loss of heterozygosity that results from acquired monosomy of chromosome 16 and perhaps other chromosomes may contribute to expression of complex genetic traits such as essential hypertension, in which the diverse phenotypic manifestations are poorly understood.

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases.

PURPOSE: The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2alpha), as possible markers of prognostic significance. METHODS: From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases. RESULTS: The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2alpha. Spearman's correlation co-efficient was 0.86 with P=0.001 ( n=17). CONCLUSIONS: In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fisher's exact test, P=0.02).