Avalia??o da express?o de telomerase (hTert), Ki-67 e P16iNK4a em les?es intraepiteliais cervicais de baixo e alto grau

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS ([email protected]) on 2016-11-16T13:11:07Z No. of bitstreams: 1 DIS_ANA_PAULA_SZEZEPANIAK_GOULART_COMPLETO.pdf: 1331186 bytes, checksum: c62191ee8989facb5039525bce1735d3 (MD5)Made available in DSpace on 2016-11-16T13:11:08Z (GMT). No. of bitstreams: 1 DIS_ANA_PAULA_SZEZEPANIAK_GOULART_COMPLETO.pdf: 1331186 bytes, checksum: c62191ee8989facb5039525bce1735d3 (MD5) Previous issue date: 2016-08-26Objective: To evaluate association between histological grade of low (CIN I) and high-grade intraepithelial cervical lesions (CIN II and III) and the immunohistochemical expression of p16INK4a, hTert and ki67 in order to establish the behavior of these lesions and recurrence during follow-up of two years. Patients and Methods: a historical cohort study of 94 women to analyze 3 groups of patients with low (CIN I) and high-grade (CIN II and III) cervical intraepithelial lesions underwent to knife, to determine the recurrence of disease associated to expression of immunohistochemical markers p16INK4a, Ki67 and hTERT. Results: Mean age of the patients was 38.2 years. Patients with CIN I, there was a lower p16INK4a expression, while in patients CIN II or I / II a higher frequency of p16INK4a ?10% was observed. In patients with CIN III there was a higher frequency of p16INK4a expression (> 50%). There were more patients with Ki67 ?10% of the cell population and lower frequency of Ki67 expression (> 50%) in CIN I. In CIN III there were fewer patients in the category Ki67 ?10% and CIN II and III group there were more patients with absent expression of Ki67. There wasn't association between hTert and histological grade. When comparing the markers between subjects with and without recurrence there was no statistically significant difference. Conclusion: There was a statistically significant association between p16INK4a, P16iNK4aM and Ki67 and histological grade, however there was no statistical difference in the expression of these markers in relation to recurrence of disease during the study period.Objetivo: Avaliar a associa??o entre gradua??o histol?gica e a express?o imunoistoqu?mica para P16iNK4a, hTert e ki67, a fim de estabelecer o comportamento dessas les?es quanto ? recorr?ncia durante o seguimento de dois anos. Pacientes e M?todos: Estudo de coorte hist?rica incluindo 94 mulheres, em que foram analisados 3 grupos de pacientes com les?es intraepiteliais cervicais de baixo (NIC I) e alto grau , classificadas em NIC II e III, submetidas ? coniza??o, a fim de determinar a recorr?ncia da doen?a conforme a express?o dos marcadores imunoistoqu?micos P16iNK4a, Ki67 e hTert. Resultados: A idade m?dia das pacientes foi de 38,2 anos. Nas pacientes com NIC I, houve maior frequ?ncia de P16iNK4a ausente, nas pacientes NIC II ou I/II observou-se maior frequ?ncia com P16iNK4a ?10%. Nas pacientes NIC III observou-se maior frequ?ncia de express?o de P16iNK4a (>50%). Na categoria NIC I houve mais pacientes com Ki67 ?10% e menor frequ?ncia de Ki67 (>50%). Na categoria NIC III houve menos pacientes na categoria Ki67 ?10% e no grupo NIC II e III houve mais pacientes com Ki67 ausente. N?o houve associa??o entre a express?o do marcador imunoistoqu?mico hTert e gradua??o histol?gica. Quando comparadas as express?es dos marcadores entre sujeitos com e sem recorr?ncia, n?o houve diferen?as estatisticamente significativas. Conclus?o: Houve uma associa??o estatisticamente significativa entre P16iNK4a, P16iNK4aM e Ki67 e a gradua??o histol?gica, entretanto n?o houve diferen?a estat?stica na express?o desses marcadores em rela??o ? recorr?ncia da doen?a no per?odo avaliado

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

ABSTRACT Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. Results : the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. Conclusion : there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated

Cotinine and Polycyclic Aromatic Hydrocarbons Levels in the Amniotic Fluid and Fetal Cord at Birth and in the Urine from Pregnant Smokers

<div><p>Cigarette smoking during pregnancy has several impacts on fetal development, including teratogenic effects. The objective of this study was to assess whether the toxic substances (cotinine and polycyclic aromatic hydrocarbons) found in pregnant smokers are transmitted to their fetuses. The outcomes were analyzed measuring cotinine and 1-hydroxypyrene in the amniotic fluid and maternal urine, benzopyrene and cotinine in the umbilical cord blood. Through a controlled cross-sectional design, 125 pregnant women were selected and classified according to their smoking status: 37 current smokers, 25 passive smokers and 63 non-smokers (controls). We performed high-performance liquid chromatography to measure substances’ concentrations. A post-hoc Tukey’s test was used to analyze the differences between the groups. All variables were significantly different between controls and smokers. The mean ratios between the concentration of cotinine in smokers compared to controls were as follows: 5.9 [2.5–13.5], p<0.001 in the urine; 25 [11.9–52.9], p<0.001 in the amniotic fluid; and 2.6 [1.0–6.8], p = 0.044 in the umbilical cord blood. The mean ratios of 1-hydroxypyrene concentration between smokers and controls were 7.3 [1.6–29.6], p = 0.003 in the urine and 1.3 [1.0–1.7], p = 0.012 in the amniotic fluid, and of benzopyrene in umbilical cord blood was 2.9 [1.7–4.7], p<0.001. There were no significant differences between controls and passive smokers. When comparing the three groups together, there were statistical differences between all variables. Thus, the fetuses of pregnant smokers are exposed to toxic and carcinogens substances. To our knowledge, this is the first study to measure 1-hydroxypyrene in the amniotic fluid and benzopyrene in umbilical cord blood by high-performance liquid chromatography when considering pregnant women in relation to smoking exposure only.</p></div

Geometric mean and standard geometric deviation of groups.

<p>Data are presented as geometric mean (GM) and geometric standard deviation (GSD).</p><p>Geometric mean and standard geometric deviation of groups.</p

Patients and fetal birth characteristics.

<p>Data are presented as means +/− standard deviations. BMI (Body Mass Index). Apgar score index. is a method for assessing a neonate’s heart rate, respiratory effort, muscle tone, skin color, and reflex irritability.</p><p>Patients and fetal birth characteristics.</p

Group comparisons of selected variables according to smoking habit.

<p>The data are presented as geometric means (minimum-maximum) or mean ratios (MRs) and [95% CI]. P: statistical significance obtained from analysis of variance model with robust standard error applied to the logarithms of the measurement. Legend: C, control; PS, passive smoker; S, smoker; MR mean ratio, ND not detected. Letters denote significant difference between groups (Tukeýs post-hoc test). a: without statistical significant difference (similar groups), b: groups with statistical difference.</p><p>Group comparisons of selected variables according to smoking habit.</p