HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.

In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

HIV-1 prevalence and risk factors among sexually transmitted disease clinic attenders in Trinidad.

OBJECTIVES: To study trends in prevalence and to ascertain risk factors for HIV-1 among sexually transmitted disease (STD) clinic attenders in Trinidad. DESIGN AND METHODS: Serial cross-sectional studies were conducted in 1987-1988 and 1990-1991 at a centralized STD clinic in Port of Spain. A case-control study was carried out to examine in greater detail the demographic and behavioral risk factors for HIV-1 among self-declared heterosexuals in this population. RESULTS: HIV-1 prevalence increased from 3.0% [95% confidence interval (CI), 2.3-3.9] in 1987-1988 to 13.6% (95% CI, 11.8-15.6) in 1990-1991. Age > or = 40 years [odds ratio (OR), 2.0; 95% CI, 1.4-2.8], urban residence (OR, 2.2; 95% CI, 1.6-3.0), and human T-lymphotropic virus-I seropositivity (OR, 3.1; 95% CI, 1.6-6.0) were significant risk factors for HIV-1 in 1990-1991. In the case-control analysis, significant independent risk factors for men included current genital ulcer disease (OR, 5.2; 95% CI, 2.2-12.5), current genital warts (OR, 3.9; 95% CI, 1.2-12.0), having ever had syphilis (OR, 3.2; 95% CI 1.6-6.1), and use of crack cocaine in the preceding 6 months (OR, 6.2; 95% CI, 2.7-14.2). Corresponding risk factors for women were commercial sex work (OR, 5.7; 95% CI, 1.3-25.7), initiation of sexual activity before age 14 years (OR, 4.8; 95% CI, 1.5-16.0), and past non-gonococcal cervicitis (OR, 4.1; 95% CI, 1.3-13.1). CONCLUSIONS: HIV-1 in this setting is primarily heterosexually transmitted in a milieu of unprotected sexual activity fuelled by a crack cocaine epidemic. Targeted interventions to prevent, detect and treat STD and crack cocaine addiction, as well as disrupt their adverse synergism, may substantially reduce HIV-1 transmission in this population.

PIP: During mid-1987 to mid-1988 and mid-1990 to mid-1991, researchers conducted cross sectional serological surveys at the STD clinic in Port of Spain in Trinidad to examine trends in HIV-1 prevalence among 2019 and 1606 STD patients, respectively. They also conducted a case control study of risk factors for HIV-1 infection among heterosexual STD patients (131 cases and 173 age- and sex-matched controls) in 1992-1993. Between 1987-1988 and 1990-1991, HIV-1 seroprevalence increased markedly (3% to 13.6%). It increased more in women than in men (9- vs. 4-fold). During 1987-1988, men were more likely to be infected with HIV-1 (odds ratio [OR] = 3.1), but by 1990-1991, gender was no longer a significant risk factor (OR = 1.3). In 1990-1991, significant risk factors for HIV-1 infection were urban residence (OR = 2.2), HTLV-1 infection (OR = 3.1), and being at least 40 years old (OR = 1.8). None of these risk factors were significant in 1987-1988. HIV-1/HTLV-1 coinfection increased between the two surveys (0.05% to 1.5%). Significant independent HIV-1 risk factors in men identified in the case control study were: used crack cocaine in the past 6 months (adjusted OR [AOR] = 6.2; p = 0.0001); ever had anal sex (AOR = 7.2; p = 0.003); ever had syphilis (AOR = 3.2; p = 0.02); current genital ulcer disease (AOR = 5.2; p = 0.0001); and current genital warts (AOR = 3.9; p = 0.02). Significant independent HIV-1 risk factors in women were: less than 14 years old at first sex (OR = 4.8; p = 0.01); ever been a commercial sex worker (AOR = 5.7; p = 0.02); and ever had nongonococcal cervicitis (AOR = 4.1; p = 0.005). These findings suggest that sexual exposure to HIV-1 through ulcers for men and inflammatory STD and/or prostitution for women, all fueled by the crack cocaine epidemic, account for much of HIV-1 exploding in Trinidad. Public health interventions to prevent, detect, and treat STDs and crack cocaine addition may greatly reduce HIV-1 transmission.

A study of HTLV-I and its associated risk factors in Trinidad and Tobago.

Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection.

Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression.

The immunologic and virologic factors that impact on the rate of disease progression after acute infection with human immunodeficiency virus (HIV) type 1 are poorly understood. A patient with an extraordinarily rapid disease course leading to AIDS-associated death within 6 months of infection was studied intensively for the presence of anti-HIV immune reactivities as well as changes in the genetic and biologic properties of virus isolates. Although altered humoral responses were evident, the most distinctive immunologic feature was a nearly complete absence of detectable HIV-specific CTL responses. In addition to a rapid decline in CD3+CD4+ cells, elevated percentages of CD8+CD45RA+ and CD8+CD57+ cells and diminished CD8+CD45R0+ and CD8+CD28+ cells were evident. Primary viral isolates recovered throughout the course of infection exhibited limited sequence diversity. Cloned viral envelopes were found to have unusually broad patterns of coreceptor usage for cell-cell fusion, although infectivity studies yielded no evidence of infection via these alternative receptors. The infectivity studies demonstrated that these isolates and their envelopes maintained an R5 phenotype throughout the course of disease. The absence of demonstrable anti-HIV CTL reactivities, coupled with a protracted course of seroconversion, highlights the importance of robust HIV-specific immune responses in the control of disease progression.

Comparison of HHV-6 antibody titers in West Africa and the Caribbean.

Human herpesvirus-6 (HHV-6) infection seems to be ubiquitous early in life, but antibody responses vary by geographic area. We compared HHV-6 antibody titer in 123 West African and 122 Caribbean serum samples. A quantitative immunofluorescence assay (IFA) using antigens derived from an HSB-2 cell line was used to test for IgG HHV-6 (GS strain) antibodies. The prevalence of HHV-6 antibodies was high (98%) in both sites. African samples had a significantly higher geometric mean titer (GMT: 697) than did Caribbean samples (GMT: 99). There was no difference between males (GMT: 260) and females (GMT: 270) overall. Children up to and including 9 years old had significantly higher titers (GMT: 483) than did all others (GMT: 237), and female children tended to have higher titers than did male children. In both areas there was a trend towards highest titer at younger age, followed by a decrease in titer during adulthood and middle age, and a secondary rise in titer in the oldest age group. Environmental and host factors may explain these geographic differences in antibody responses between two groups of African origin.

HHV-6 infection in patients with HIV-1 infection and disease.

Human herpesvirus 6 (HHV-6) is among the most widespread of the human herpesviruses. In immunocompetent children, it causes exanthem subitum, febrile episodes without skin rash, and non-Epstein-Barr and non-cytomegalovirus infectious mononucleosis. HHV-6 has also been associated with clinical disease in bone marrow and solid organ transplant recipients. Its potential role in HIV-1-associated clinical syndromes is now being recognized and evaluated. In this review, we describe the virus, the pathogenesis of HHV-6-associated disease, and the diagnostic tests used to differentiate active from latent infection. We then discuss possible clinical manifestations of HHV-6 in HIV-1-infected patients, how to evaluate the need for treatment, and which pharmacologic agents are potentially useful. There is no consensus on these issues in the medical community, and HHV-6 is not now included among indicator infections for the diagnosis of AIDS.

Retroviruses in the Caribbean.

Transmission of HIV in many Caribbean countries has followed the pattern of initial predominance among homosexual and bisexual males, with the infection subsequently spreading into the heterosexual community. However, on Saint Lucia the epidemic began among heterosexual contacts of Saint Lucian laborers from Florida; in Bermuda 58% of AIDS cases have been in intravenous drug abusers; and in the Bahamas 59% of the AIDS patients have been heterosexuals and 19% children infected via the perinatal route. Seroprevalence of the human T-lymphotropic virus, type 1 (HTLV-I), whose modes of transmission resemble those of HIV, has been found to range from 2.3% in Trinidad and Tobago to 5.4% in Jamaica. In a study of HIV and HTLV-1 infection patterns in homosexual males in Trinidad and Tobago, the cohort was too small for confirmation that coinfection with these two viruses hastened progression in AIDS, but further investigation is warranted.

Human T-cell lymphotropic virus type I-associated facial nerve palsy in Trinidad and Tobago.

To assess the association of the human T-cell lymphotropic virus type I (HTLV-I) and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78 patients consecutively admitted to the Port of Spain General Hospital in Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve palsy. Patients were compared with two control groups: a population-based group of persons 20 years and older and a hospital-based group of patients 15 to 84 years old admitted to the medical wards. Sixty-two patients were Trinidadians of African origin and 16 were Trinidadians of East Indian origin. None of the East Indian patients was HTLV-I antibody positive. Three Afro-Trinidadians were infected with human immunodeficiency virus type 1 and 1 was coinfected with this virus and HTLV-I. Of the remaining 58 Afro-Trinidadians, 12 (20.7%) were HTLV-I positive only. This rate was statistically higher than the HTLV-I seroprevalence in the Afro-Trinidadian general population (3.5%) and the hospital control group (5.6%). After age standardization, the HTLV-I prevalence for patients with facial nerve palsy remained significantly elevated. HTLV-I antibody assays should be performed on all patients with idiopathic facial nerve palsy of the lower motor neuron type who live in HTLV-I endemic areas or are migrants from these areas.

HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis.

OBJECTIVES: It has been shown that > 90% of mothers of HTLV-I-infected children were themselves carriers of HTLV-I. This study was designed to determine the HTLV-I serostatus of mothers of patients with adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and to assess the association of age of exposure and disease outcome. STUDY DESIGN/METHODS: In a cross-sectional study of the HTLV-I serostatus of mothers of HTLV-I-seropositive patients with ATL and HAM/TSP, 36 living mothers of patients with ATL and 15 mothers of patients with TSP/HAM were traced and enrolled. RESULTS: Five of the 15 (33%) mothers of patients with HAM/TSP and 35 of the 36 (97.2%) mothers of patients with ATL were HTLV-I-seropositive. All patients were breast-fed and none received blood transfusions. CONCLUSION: This study confirms that infection with HTLV-I in early childhood can lead to ATL in later life, and that HAM/TSP can also result from early infection but more commonly results from infection acquired in adulthood. There are several reports of posttransfusion HAM/TSP, but ATL has not been reported following blood transfusion except in patients who were immunocompromised. Because the newborn infant is considered to be immunoincompetent, it seems that this is a necessary factor for the development of ATL after infection.

Cutaneous histoplasmosis in the acquired immune deficiency syndrome--a report of three cases from Trinidad.

Three cases are reported of patients with the Acquired Immune Deficiency Syndrome (AIDS) and cutaneous histoplasmosis. Their initial presentation was that of a generalised maculopapular rash. Two patients were bisexual males and the third was an unmarried female. The range of opportunistic infections seen in AIDS patients in Trinidad is mentioned and clinicians are alerted to the fact that in areas endemic for Histoplasma capsulatum maculopapular rash in patients with AIDS may suggest disseminated histoplasmosis. The value of skin biopsy is mentioned.

Transmission of HTLV-I and HIV among homosexual men in Trinidad.

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.

Role of HTLV-I in development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago. The HTLV Lymphoma Study Group.

Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enrolled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95% CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-167]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80% cases of NHL in people under 60 years in this region.

Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody.

The VIDAS HIV DUO Ultra, a fourth-generation immunoassay under development for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 and HIV-2, was evaluated. The enzyme-linked fluorescence immunoassay, performed on the automated VIDAS instrument, is claimed to detect early and established HIV infection. The assay was challenged with a total of 2,847 samples that included 74 members of 10 seroconversion panels, 9 p24 antigen-only-reactive members of a panel of group M clades, 503 consecutively collected samples from individuals seeking care in the University of Maryland Medical System, 1,010 samples from U.S. blood donors, 1,141 samples from patients in a high-incidence population in Trinidad, 83 samples from a clinic for sexually transmitted diseases in the Bahamas, 10 confirmed HIV-1 group O samples, and 16 confirmed HIV-2 samples from the Cote d'Ivoire. Reference tests were U.S. Food and Drug Administration-licensed HIV antibody screening, p24 antigen tests, HIV confirmatory assays, and the Roche Diagnostics Amplicor HIV-1 Monitor. The VIDAS HIV DUO Ultra demonstrated 100% sensitivity and 99.5% specificity overall, with a 99.7% specificity in low-risk individuals. The analytical sensitivity, as assessed by seroconversion panels and p24 antigen in samples, was equivalent to the sensitivity of the reference assays used to characterize these panels. The VIDAS HIV DUO Ultra is accurate, offers potential advantages over conventional HIV testing for time and cost savings, has walk-away capability, and correctly identifies both early and established HIV infections.

Higher macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels from CD8+ T cells are associated with asymptomatic HIV-1 infection.

To test the hypothesis that beta-chemokine levels may be relevant to the control of HIV in vivo, we compared RANTES, MIP-1alpha, and MIP-1beta production from purified CD8(+) T cells from 81 HIV-infected subjects and from 28 uninfected donors. Asymptomatic HIV(+) subjects produced significantly higher levels of MIP-1alpha and MIP-1beta, but not RANTES, than uninfected donors or patients that progressed to AIDS. In contrast, beta chemokines in plasma were either nondetectable or showed no correlation with clinical status. The high beta-chemokine-mediated anti-HIV activity was against the macrophage tropic isolate HIV-1(BAL), with no demonstrable effect on the replication of the T-cell tropic HIV-1(IIIB). These findings suggest that constitutive beta-chemokine production may play an important role in the outcome of HIV-1 infection.

Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad.

HTLV-I is sexually transmitted more efficiently from men to women than vice versa, and the majority of HTLV-I endemic areas report a female preponderance of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) cases. The objective of this study was to estimate the gender- and age-specific incidence rates of HAM/TSP in the general population as well as in the HTLV-I-infected population in Jamaica and in Trinidad and Tobago. Incidence rates for HAM/TSP were computed based on all reported incident cases in both countries between 1990 and 1994. Population census reports for 1990 were used to calculate the population at risk. The age-standardized HAM/TSP incidence rate (mean +/- standard error of the mean) in Jamaica was 1.8 +/- 0.2/100,000 person years (PY). Among individuals of African descent in Trinidad and Tobago, the rate was 1.7 +/- 0.4/100,000 PY. As in HTLV-I seroprevalence, the incidence rate of HAM/TSP increased with age through the fifth decade of life and was three times as high in women than in men. The HAM/TSP incidence rate, calculated as a function of the number of HTLV-I-infected persons in each age stratum, is higher in women (24.7/100,000 PY) than in men (17.3/100,000 PY). With HTLV-I infection, the lifetime risk of developing HAM/TSP was estimated to be 1.9% overall and is slightly higher in women (1.8%) than in men (1.3%). Thus, the higher prevalence of HTLV-I in women in endemic areas does not fully explain the preponderance of female HAM/TSP, suggesting that other cofactors must be present. The higher incidence rate in women between the ages of 40 and 59 years, as well as the increase in HAM/TSP incidence rates with age, are indicative of the importance of adult-acquired HTLV-I infection, presumably through sexual transmission.

Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

Geographic diversity of adult t-cell leukemia/lymphoma in Brazil. The Brazilian ATLL Study Group.

We describe 195 cases of adult T-cell leukemia/lymphoma (ATLL) reported to the national registry of T-cell malignancies in Brazil between 1994 and 1998. We compared the effect of demographic differences and clinical features of 150 consecutive ATLL cases in different regions of this diverse country. At diagnosis, the predominant clinical sub-type was the acute type (60%), followed by lymphoma (22%), chronic (10%) and smoldering (8%) types. Although we expected that different sub-types would be present in different regions, on the basis of immunogenetic factors determined by ethnicity, we did not demonstrate these differences. There were no significant differences among ATLL subtypes by age or gender. No ethnic group predominated in the total population of patients, but significant differences were noted when examining ethnic distribution by region. Reflecting the general population distribution, white patients were seen more often in São Paulo and black patients in Bahia, than in other regions. In most regions, cases were equally distributed between blacks and mulattos, except in Pernambuco, where blacks were less frequent. The main clinical features were lymphadenopathy, skin lesions, hypercalcemia and hepatomegaly. Fourteen patients (9%) suffered from HTLV-I-associated myelopathy (HAM/TSP), either at diagnosis or during follow-up of ATLL. All cases but one had antibodies to HTLV-I, with concordant results with ELISA, WB and PCR analyses. For the antibody-negative case, pol and tax gene sequences were present in tumor cells when subjected to PCR analyses. The prognosis was generally poor, suggesting that the disease in Brazil behaves in similar fashion regardless of ethnic or geographical differences.