Publications by authors named "Sheila Jorge Adad"

53 Publications

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

Pathobiology 2021 Oct 12:1-9. Epub 2021 Oct 12.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC).

Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals.

Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology.

Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics.

Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
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http://dx.doi.org/10.1159/000518697DOI Listing
October 2021

Histoplasmosis in HIV-Infected Patients: Epidemiological, Clinical and Necropsy Data from a Brazilian Teaching Hospital.

Mycopathologia 2020 Apr 20;185(2):339-346. Epub 2020 Feb 20.

Infectious Diseases Unit, Internal Medicine Department, Triângulo Mineiro Federal University, Mailbox 118, Uberaba, Minas Gerais, 38001-170, Brazil.

Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.
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http://dx.doi.org/10.1007/s11046-020-00435-yDOI Listing
April 2020

Main findings and diagnostic yield of bronchoalveolar lavage, bronchial brushing and transbronchial biopsy in HIV-positive patients.

Rev Inst Med Trop Sao Paulo 2019 25;61:e61. Epub 2019 Nov 25.

Universidade Federal do Triângulo Mineiro, Departamento de Clínica Cirúrgica, Uberaba, Minas Gerais, Brazil.

Bronchoalveolar lavage, bronchial brushing and transbronchial biopsy are of fundamental importance in the diagnosis of pathologies affecting the lungs of immunosuppressed patients, especially those infected with HIV. This was a descriptive and retrospective study, in which the results of bronchoalveolar lavages, bronchial brushings and transbronchial biopsies of HIV-positive patients attended at the Clinical Hospital of the Federal University of Triangulo Mineiro from 1999 to 2015 were reviewed to determine the most frequent findings in these patients, to evaluate the diagnostic accuracy of these procedures and to correlate bronchoscopy results with clinical and radiological findings. Serological tests for HIV were confirmed and cases with negative or unverified serology were excluded. Medical records were reviewed for correlation with clinical and radiological findings. A total of 1,423 patients with a mean age of 50 years were initially selected; 727 cases had no serology for HIV; 696 had serology for HIV and 64 were positive. Of these, 47 were men, aged 24 to 84 years, and 17 women, aged 31 to 69 years. Biopsies and cytological tests were positive in 20 (31.25%) of the 64 patients and the most frequent diagnosis was pneumocystosis, found in 8 cases (12.5%). Of the 20 bronchofibroscopy-positive patients, only 2 did not show agreement between histopathological and clinical-radiological diagnoses. The analysis of the cytological tests and biopsy specimens obtained by bronchofibroscopy seems to be valuable for the etiological diagnosis of pulmonary infections in HIV- positive patients; however, negative results do not always exclude the diagnosis. In these cases, clinical symptoms and imaging findings may help to guide the best therapy.
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http://dx.doi.org/10.1590/S1678-9946201961061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880975PMC
December 2019

Clinical and anatomopathological aspects of patients with hantavirus cardiopulmonary syndrome in Uberaba, Minas Gerais, Brazil.

Rev Inst Med Trop Sao Paulo 2019 10;61:e55. Epub 2019 Oct 10.

Universidade Federal do Triângulo Mineiro, Departamento de Clínica Cirúrgica, Uberaba, Minas Gerais, Brazil.

The hantavirus cardiopulmonary syndrome is considered an emerging disease in the Americas. Since 1993, thousands of cases have been reported from different countries, but mainly from Brazil. This study aims to describe some epidemiological, clinical and anatomopathological aspects of patients with hantavirus who presented poor outcome and were autopsied in a teaching hospital in Brazil, from 2000 to 2014. Of the 10 patients included, nine were male (mean age 43.5 years) and seven reported previous contact with rodents. Fever was present in eight of ten patients, dyspnea in nine of ten and myalgia in seven of ten patients; hemoconcentration, leukocytosis, thrombocytopenia and renal involvement were evidenced in all the 10 cases. At autopsy, the main alterations were seen in the lungs: pleural effusion (8/10 cases), increased weight 2.5 to 3 times, congestion/edema (10/10), interstitial mononuclear inflammation (10/10), alveolar hemorrhage (7/10), pulmonary collapse (7/10), hyaline membranes (7/10) and alveolar neutrophilic infiltrate (2/10). Pericardial effusion (2/10), mild myocardium inflammation (4/10), right ventricle dilation (1/10), polyploidy nuclei (3/10) and pericardial diffuse petechial (1/10) were also observed. The other organs exhibited discrete and non-specific alterations. Currently, this syndrome continues to be associated with high mortality directly linked to a late diagnosis and/or a misdiagnosis in the medical centers where these patients were seen for the first time. The anatomopathological findings at autopsy revealed the final phase of the process with pulmonary alterations, allowing a direct correlation with the severity of respiratory distress observed in these patients at admission.
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http://dx.doi.org/10.1590/S1678-9946201961055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792360PMC
October 2019

Arginase-1 and Treg Profile Appear to Modulate Inflammatory Process in Patients with Chronic Gastritis: May Be the Alarm Cytokine in -Positive Patients.

Mediators Inflamm 2019 20;2019:2536781. Epub 2019 Jun 20.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil.

() is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing infection. This study is aimed at analyzing the mRNA expression of the cytokines , , , , , , , and ; transcription factors , , and ; enzymes , , and ; and neuropeptides and and their respective receptors and in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the gene and its transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of , , , and and the transcription factors, and , in the presence or absence of showed no significant difference. However, the expression of was significantly lower in -positive patients than that in -negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.
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http://dx.doi.org/10.1155/2019/2536781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610761PMC
February 2020

mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome.

Infect Agent Cancer 2018 29;13:43. Epub 2018 Dec 29.

1Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, SP CEP 14784 400 Brazil.

Background: Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.

Objective: We analyzed hotspot gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of mutations with patients' clinical and pathological features.

Methods: The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.

Results: mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between mutations and patients' clinical features or mutation profile.

Conclusion: This is the first report on the presence of mutations in esophageal cancer associated with chagasic megaesophagus. The detection of mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.
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http://dx.doi.org/10.1186/s13027-018-0216-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311070PMC
December 2018

Presence of microsatellite instability in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

Biomark Med 2018 06 6;12(6):573-582. Epub 2018 Jun 6.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.

Aim: The molecular pathogenesis of esophageal squamous cell carcinoma (ESCC) has been increasingly studied, but there is no report on the role of MSI in ESCC development associated with chagasic megaesophagus (CM).Results/methodology: In four ESCC/CM (4/19) we found microsatellite instability (MSI) alterations (21.1%), being three MSI-L (15.8%) and one MSI-H (5.3%). Four out of 35 ESCC cases showed MSI-L (11.4%) and only one out of 26 CM cases presented MSI-L (3.9%). The MSI-H was observed in an ESCC/CM patient that presents lack of MSH6 immunostaining corroborating deficiency in MMR pathway. Interestingly, the MSI-H ESCC/CM case also presented a deletion the HSP110 poly(T)17 gene.

Discussion/conclusion: Taking together, we concluded that MSI is a rare event in esophageal squamous cell carcinoma, but can be associated with CM.
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http://dx.doi.org/10.2217/bmm-2017-0329DOI Listing
June 2018

Modulation of Galectin-3 and Galectin 9 in gastric mucosa of patients with chronic gastritis and positive Helicobacter pylori infection.

Pathol Res Pract 2017 Oct 25;213(10):1276-1281. Epub 2017 Aug 25.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, CEFORES, Brazil. Electronic address:

Objectives: Galectins are mediators that play an important role in the inflammatory response and in this study we analyzed the expression of Galectins (Gal) -1, -3 and -9 in biopsies of the gastric antrum of patients with upper gastrointestinal symptoms.

Methodology: 44 patients with upper digestive tract symptoms were evaluated, and underwent Upper Digestive Endoscopy examination. Sections of the gastric antrum were fixed in buffered formaldehyde at 4% in order to perform the anatomopathological examination and immunohistochemical analysis for Galectins-1, -3 and -9 expression. Fresh sections of gastric antrum were used for DNA extraction and evaluation of Helicobacter pylori (H. pylori). P values<0.05 were considered statistically significant.

Results: Gal-1 was significantly more expressed on stroma than epithelium (p<0.0001), whereas Gal-3 and Gal-9 were more expressed on epithelium (p<0.0001). Gal-3 was found to be significantly higher in the stroma of patients with H. pylori infection, mainly on Cag-A positive H. pylori (p<0.0001). Gal-9 was down modulated in stroma of patients with chronic gastritis.

Conclusion: Up modulation of Gal-3 expression was associated with H. pylori infection and down modulation of Gal-9 with the inflammatory process of chronic gastritis.
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http://dx.doi.org/10.1016/j.prp.2017.08.005DOI Listing
October 2017

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy).

Rev Inst Med Trop Sao Paulo 2017 Apr 3;59:e3. Epub 2017 Apr 3.

Universidade Federal do Triângulo Mineiro, Departamento de Patologia Especial, Uberaba, Minas Gerais, Brazil.

Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.
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http://dx.doi.org/10.1590/S1678-9946201759003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441154PMC
April 2017

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil.

Am J Trop Med Hyg 2016 10 25;95(4):781-785. Epub 2016 Jul 25.

Infectious Diseases Unit, Triângulo Mineiro Federal University, Minas Gerais, Brazil.

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training.
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http://dx.doi.org/10.4269/ajtmh.16-0148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062772PMC
October 2016

Comparison of Classical and Secondary Cytologic Criteria Relative to Hybrid Capture for Diagnosing Cervical-vaginal Infection by Human Papillomavirus.

Rev Bras Ginecol Obstet 2016 Jan;38(1):41-6

UFTM, Uberaba, Minas Gerais, Brazil.

Objective: To compare the diagnostic accuracy of the classic Meisels cytologic criteria and the Schneider secondary criteria relative to the hybrid capture method for diagnosing HPV infection.

Methods: This was a retrospective study performed at a public university hospital. A total of 41 patients with a cytologic diagnosis of HPV infection and 40 HPV-negative patients were selected for review of the cervical-vaginal smears seeking to classical and secondary criteria. A single pathologist reviewed the slides in search of the criteria. The classical and secondary cytologic criteria were compared with the hybrid capture for diagnosing HPV infection. Bartleti test was applied for the age analysis, and Fisher's exact test was used to compare proportions. The tests were considered significant when the probability of rejecting the null hypothesis was less than 5% (p < 0.05).

Results: The Meisels criteria were less sensitive (34.0%) than the secondary Schneider criteria (57.5%) when compared with the hybrid capture (p < 0.0001), although the specificity of the former criteria was non-significantly higher (91.2% and 67.7%, respectively). In cases of moderate or intense inflammation, the sensitivity and specificity of the Schneider criteria were decreased, 33.3% and 50.0% respectively (p = 0.0115).

Conclusions: Compared with hybrid capture for diagnosis of HPV infection, the sensitivity of the secondary Schneider criteria was higher than the classical Meisels criteria.Moderate or intense inflammation reduces the sensitivity and specificity of the secondary Schneider criteria for diagnosing HPV infection using the hybrid capture as the gold standard.
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http://dx.doi.org/10.1055/s-0035-1570105DOI Listing
January 2016

Immunohistochemical staining of tumor necrosis factor-α and interleukin-10 in benign and malignant ovarian neoplasms.

Oncol Lett 2015 Feb 8;9(2):979-983. Epub 2014 Dec 8.

Research Institute of Oncology (IPON)/Discipline of Gynecology and Obstetrics, Federal University of Triângulo Mineiro (UFTM), 38025-440 Uberaba, MG, Brazil.

Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher's exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy.
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http://dx.doi.org/10.3892/ol.2014.2781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301559PMC
February 2015

Blood vessels in ganglia in human esophagus might explain the higher frequency of megaesophagus compared with megacolon.

Rev Inst Med Trop Sao Paulo 2014 Nov-Dec;56(6):529-32

Resident, Universidade Federal do Triangulo Mineiro, Uberaba, MG, Brazil.

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296875PMC
http://dx.doi.org/10.1590/s0036-46652014000600013DOI Listing
April 2015

Correlation of cytokines and inducible nitric oxide synthase expression with prognostic factors in ovarian cancer.

Immunol Lett 2014 Mar-Apr;158(1-2):195-9. Epub 2014 Jan 18.

Research Institute of Oncology (Instituto de Pesquisa em Oncologia)/Discipline of Gynecology and Obstetrics, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil. Electronic address:

The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients.
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http://dx.doi.org/10.1016/j.imlet.2014.01.005DOI Listing
November 2014

Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer.

Clinics (Sao Paulo) 2013 Jun;68(6):809-14

Araújo Jorge Hospital, Goiás Anticancer Association, Goiânia/GO, Brazil.

Objective: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis.

Methods: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival.

Results: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p=0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p=0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18.

Conclusion: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy.
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http://dx.doi.org/10.6061/clinics/2013(06)14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674251PMC
June 2013

An imbalance between substance P and vasoactive intestinal polypeptide might contribute to the immunopathology of megaesophagus after Trypanosoma cruzi infection.

Hum Pathol 2013 Feb 17;44(2):269-76. Epub 2012 Sep 17.

Department of Morphology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31.270-901, Brazil.

Megaesophagus is one of the major causes of morbidity in chronic Chagas disease, and extensive denervation, associated with an inflammatory process, is recognized as the key factor for alterations in motility and disease development. Here, we analyzed esophagus samples from necropsied, infected individuals--6 cases with megaesophagus and 6 cases without megaesophagus--for the relative areas of expression of 2 neuromediators, substance P and vasoactive intestinal peptide, which are known to activate or inhibit, respectively, local immune cells. Samples from 6 noninfected individuals were used as controls. Esophageal sections were immunohistochemically stained for protein gene product 9.5, vasoactive intestinal peptide, and substance P, and the relative areas of expression of the latter 2 were calculated. Morphometric analyses revealed increased substance P and decreased vasoactive intestinal peptide relative areas in esophageal sections from patients with megaesophagus. Furthermore, in the group of patients without megaesophagus, the loss of vasoactive intestinal peptide positively correlated with the denervation process. We suggest that an imbalance between vasoactive intestinal peptide and substance P production results in the reestablishment and maintenance of the inflammatory process, leading to denervation and, consequently, promoting the development of megaesophagus.
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http://dx.doi.org/10.1016/j.humpath.2012.05.020DOI Listing
February 2013

The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM.

Virchows Arch 2012 Oct 16;461(4):385-92. Epub 2012 Aug 16.

Discipline of Special Pathology, Universidade Federal do Triângulo Mineiro, Av. Getúlio Guaritá, 130, CEP 38025-440 Uberaba, MG, Brazil.

In addition to neurons, interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility with a pacemaker function. This study aimed to quantitatively analyze ICC, neurons, and muscular area, the latter to correct for quantitation errors resulting from dilation in case of a megacolon and from the dispersion of ICC that can be attributed to muscular hypertrophy. We analyzed 30 colon samples: ten chagasic megacolon (CM), ten chagasic colons without megacolon (CXM), and ten nonchagasic control patients (NC). We measured the area of muscularis propria and counted the number of neurons of the myenteric plexus in a histological section of an intestinal ring and the number of ICC at the level of the myenteric plexus and circular muscle layer, the latter in a section immunohistochemically stained for CD117. Muscular hypertrophy occurred only in the CM group. Compared to the NC group, we found in the CM group a statistically significant reduction of 80 % in the number of neurons, 60 % in the number of ICC in the myenteric plexus, and 38 % in the area of circular muscle. In the CXM group, these numbers were highly variable, and their reduction, less pronounced. We conclude that the number of ICC is significantly reduced in CM patients, and that this might contribute to the pathophysiology of CM. However, the development of CM requires severe denervation, whereas CXM generally exhibits less than 50 % denervation, favoring the hypothesis that the reduction in ICC number is, in part, a consequence of denervation.
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http://dx.doi.org/10.1007/s00428-012-1299-7DOI Listing
October 2012

Cellular fibroma of the ovary with multiloculated macroscopic characteristics: case report.

Case Rep Med 2012 11;2012:283948. Epub 2012 Apr 11.

Discipline of Special Pathology, Universidade Federal do Triangulo Mineiro (UFTM), Avenida Getulio Guarita 130, 38045-440 Uberaba, MG, Brazil.

Ovarian fibroma is the commonest benign tumor of the ovarian stroma. The cellular subtype accounts for around 10% of ovarian fibromatous tumors. The cellular fibroma is a tumor of uncertain malignant potential that may recur or be associated with peritoneal implants. Usually these are solid tumors, sometimes with small areas of cystic degeneration. This case is reported to highlight an unusual feature for an ovarian fibroma: the tumor was predominantly cystic with a small solid part; the multiple cavities contents consisted of viscous liquid that solidified under room temperature. The multiloculated cysts, the mucinous contents, and the solid areas simulated a borderline mucinous ovarian tumor on both CT scan and gross pathologic examination.
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http://dx.doi.org/10.1155/2012/283948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3332172PMC
August 2012

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study.

Rev Inst Med Trop Sao Paulo 2012 Mar-Apr;54(2):89-93

Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.
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http://dx.doi.org/10.1590/s0036-46652012000200006DOI Listing
September 2012

Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation.

AIDS Res Treat 2012 22;2012:186850. Epub 2012 Feb 22.

Discipline of Special Pathology, Universidade Federal do Triângulo Mineiro (UFTM), Avenida Getúlio Guaritá 130, 38025-440 Uberaba, MG, Brazil.

A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.
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http://dx.doi.org/10.1155/2012/186850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296154PMC
August 2012

Benign and malignant neoplasias in 261 necropsies for HIV-positive patients in the period of 1989 to 2008.

Rev Inst Med Trop Sao Paulo 2011 Nov-Dec;53(6):309-14

UFTM School of Medicine, Uberaba, MG, Brazil.

Considering that there are some studies with autopsies from AIDS describing only malignant neoplasias and that changes can occur after the introduction of Highly Active Antiretroviral Therapy (HAART), our objectives were to analyze the frequency of benign and malignant neoplasms in AIDS patients in the periods of both pre- and post-HAART. This is a retrospective study with 261 autopsies of HIV-positive patients between 1989 and 2008 in Uberaba, Brazil. Sixty-six neoplasms were found (39 benign, 21 malignant and six premalignant) in 58 patients. The most frequent malignant neoplasms were lymphoid, in 2.7% (four Non-Hodgkin lymphoma, one Hodgkin, one multiple myeloma and one plasmablastic plasmacytoma), and Kaposi's Sarcoma, in 2.3% (six cases). The most frequent benign neoplasms were hepatic hemangiomas in 11 (4.2%) of 261 cases and uterine leiomyoma in 11 (15.7%) of 70 woman. In the pre-HAART period eight (9.8%) benign neoplasias and four (4.9%) malignant occurred in 82 patients; in the post-HAART period, 29 (16.2%) benign and 17 (9.5%) malignant were present; however, the differences were not significant. We conclude that the introduction of HAART in our region doesn't look to have modified the frequency of neoplasms occurring in patients with HIV.
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http://dx.doi.org/10.1590/s0036-46652011000600002DOI Listing
September 2012

Cytokine serum levels in patients with cervical intraepithelial neoplasia grade II-III treated with intralesional interferon-α 2b.

Tumori 2011 Sep-Oct;97(5):578-84

Oncology Research Institute (IPON)/Discipline of Gynecology and Obstetrics, Federal University of the Triângulo Mineiro (UFTM), Avenida Getúlio Guaritá, s/n° Uberaba (MG), Brazil, CEP 38025-440, Bairro Abadia.

Aims And Background: Cervical intraepithelial neoplasia (CIN) grade II-III is being diagnosed in younger women and, because of the reproductive age range for women and the habits associated with a modern lifestyle, is now affecting a broad age range. Surgical treatment for CIN has been associated with premature amenorrhea, low birth weight, and premature labor and birth. It is therefore imperative to develop clinical treatments for CIN, such as conservative treatment with interferons. The object of the present study was to evaluate the behavior of cytokines (IFN- g, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF β) in the serum of patients with an initial diagnosis of CIN II-III.

Methods: Ten patients with CIN-CIN II (60%, n = 6) and CIN III (40%, n = 4), 23 to 51 years of age and who had not received any prior treatments, were evaluated. The patients were given 3 million/UI (per cm2 of colposcopic lesion) of human recombinant IFN-α 2b by intralesional administration (18 applications on alternate days). Before treatment, in the 6th, 12th, and 18th applications, blood was collected from the patients for cytokine analysis using ELISA.

Results: Half of the patients had a good pathologic response; the other half, all of whom were smokers, had therapeutic failure. The average concentration of IL-12 (pg/ml) in the serum of patients who responded well to therapy was elevated from the 12th and 18th application of IFN-α 2b compared to patients who experienced therapeutic failure: 1804.0 ± 1020 vs 391.2 ± 722.3 and 1738.0 ± 2426.0 vs 448.5 ± 407.2, respectively, P <0.05.

Conclusions: CIN II-III treated with intralesional IFN-α 2b achieved a good response in non-smoking patients and was associated with an increase in IL-12 serum levels.
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http://dx.doi.org/10.1700/989.10715DOI Listing
April 2012

Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega.

J Trop Med 2012 30;2012:232646. Epub 2011 Oct 30.

Disciplina de Patologia Especial, Universidade Federal do Triângulo Mineiro (UFTM), Avenida Getúlio Guaritá 130, Abadia 38045-440 Uberaba, MG, Brazil.

To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+).
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http://dx.doi.org/10.1155/2012/232646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206379PMC
August 2012

Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus.

Infect Dis Obstet Gynecol 2011 29;2011:904674. Epub 2011 Jun 29.

Discipline of Gynecology and Obstetrics, Oncology Research Institute, Uberaba, MG, Brazil.

Introduction: To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking.

Methods: 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed.

Results: Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031).

Conclusions: ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.
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http://dx.doi.org/10.1155/2011/904674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132509PMC
October 2011

Relationship between infectious agents for vulvovaginitis and skin color.

Sao Paulo Med J 2010 Dec;128(6):348-53

Instituto de Pesquisa em Oncologia, Discipline of Gynecology and Obstetrics, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Context And Objective: Many factors influence occurrences of vulvovaginitis. The aims here were to assess skin color and age-related differences in the vaginal flora and occurrences of vulvovaginitis.

Design And Setting: Cross-sectional study; tertiary referral hospital (Universidade Federal do Triângulo Mineiro, Uberaba).

Methods: Healthy women who underwent routine outpatient gynecological assessments were assessed for vulvovaginitis and vaginal flora and then divided into whites (n = 13,881) and nonwhites (n = 5,295). Statistical analysis was performed using the X² test, logistic regression and odds ratios.

Results: The vaginal microflora was skin-color dependent, with greater occurrence of clue cells, Trichomonas vaginalis and coccobacilli in nonwhite women (p < 0.0001). Döderlein bacilli and cytolytic flora were more prevalent in white women (p < 0.0001 and p < 0.05, respectively). The vaginal microflora was age-dependent within the skin color groups. Among the nonwhite women, clue cells were more prevalent in women aged 21 to 50 years; Trichomonas in women up to 40 years and coccobacili in women between 21 and 40 years (P < 0.05). During the proliferative and secretory phases, the nonwhite women were more likely to present clue cells, Trichomonas, Candida and coccobacilli (OR, proliferative phase: 1.31, 1.79, 1.6 and 1.25 respectively; secretory phase: 1.31, 2.88, 1.74 and 1.21 respectively), while less likely to present Döderlein flora (OR, proliferative phase: 0.76; secretory phase: 0.66), compared with white women, irrespective of age.

Conclusions: There are differences in vulvovaginitis occurrence relating to skin color, which may be associated with variations in vaginal flora.
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http://dx.doi.org/10.1590/s1516-31802010000600007DOI Listing
December 2010

Thymus cyst: an option in the differential diagnosis of cervical-mediastinal tumors.

Braz J Otorhinolaryngol 2010 Jul-Aug;76(4):538

Triangulo Mineiro Federal University, Uberaba, Minas Gerais.

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March 2011

Factors associated with recurrence of cervical intraepithelial neoplasia after conization in HIV-infected and noninfected women.

Arch Gynecol Obstet 2011 Jul 1;284(1):191-7. Epub 2010 Aug 1.

Medical Science School of Minas Gerais, Belo Horizonte, Brazil.

Purpose: To identify risk factors associated with recurrence of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedures in women with and without human immunodeficiency virus (HIV).

Methods: A total of 33 patients with recurrent CIN and 105 without recurrence were contrasted using a nested case-control design. The patients were enrolled between 1999 and 2004. Recurrence diagnosis was established after conization, and tissues were fixed in formalin and embedded in paraffin. Polymerase chain reaction was used to detect the human papillomavirus genome (HPV DNA) types 6, 11, 16, 18, 31, 33, and 35. Statistical analysis was performed using χ² test with Yates correction and the Fisher's exact test for comparison of categorical variables. Multivariate analysis was carried out using logistic regression models.

Results: Human immunodeficiency virus infection (p = 0.001), glandular involvement (p = 0.000), and compromised margins (p = 0.02) were significantly associated with CIN recurrence. HPV DNA was positive in 57.6% of patients with CIN recurrence. High-risk HPV subtypes were detected in most cases but were not associated with recurrence (p = 0.27). In multivariate analysis, HIV infection and glandular involvement were independently associated with CIN recurrence.

Conclusions: Human immunodeficiency virus infection and glandular involvement are associated with CIN recurrence.
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http://dx.doi.org/10.1007/s00404-010-1611-1DOI Listing
July 2011

Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia.

Clinics (Sao Paulo) 2010 Jun;65(6):575-81

Federal University of Triângulo Mineiro, Research Institute of Oncology, Uberaba/MG, Brazil.

Objectives: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma.

Methods: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (+/- 4.3), 35.5 (+/- 9.5), and 50 (+/- 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the infiltrating tumor. Two independent observers performed the immunohistochemical analysis.

Results: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05).

Conclusion: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.
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http://dx.doi.org/10.1590/S1807-59322010000600003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898547PMC
June 2010
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