Sônia Maria Miranda Pereira

Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.

Solid tumor cells are known to be highly glycolytic and, to prevent apoptosis by cellular acidosis, cells increase proton efflux through pH regulators, such as monocarboxylate transporters (MCTs). However, the role of these membrane proteins in solid tumor development and survival is not fully understood. We aimed to evaluate the expression of the MCT isoforms 1, 2, and 4 in a large series of cervical lesions (neoplastic and non-neoplastic) and assess its clinical-pathologic significance. The series analyzed included 29 chronic cervicitis, 30 low-grade squamous intraepithelial lesions, 32 high-grade squamous intraepithelial lesions, 49 squamous cell carcinomas, 51 adenocarcinomas, and 30 adenosquamous carcinomas of the uterine cervix. Analysis of the expression of MCT isoforms 1, 2, and 4 was performed by immunohistochemistry with specific antibodies. Immunoreactions were evaluated both qualitatively and semiquantitatively. We found a significant increase in MCT expression from preinvasive to invasive squamous lesions and from normal glandular epithelium to adenocarcinomas. This is the first study evaluating the significance of MCT expression in lesions of the uterine cervix, including invasive carcinomas, and the results found herein led us to believe that these membrane proteins are involved in the progression to invasiveness in uterine cervix carcinoma.

Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.

Simultaneous Chlamydia trachomatis and HPV infection in pregnant women.

Pregnancy is associated with HPV infection and with Chlamydia trachomatis (CT) infection mostly due to the natural immunosuppression. In addition, pregnancy associated to CT infection can lead to adverse conditions to the woman and fetus, and CT is also believed to be a co‐factor in human immunodeficiency virus infection and HPV‐induced cervical cancer. The aim of this study was to establish the odds ratios (OR) of CT infection in to HPV‐infected pregnant women and vice versa of women stratified by age (<25 years) and marital status. This work is part of a national multicentric transversal study carried out in six Brazilian cities supported by the Ministry of Health of Federal Government of Brazil in 2003. Cervical scrapes of 371 pregnant women were sampled. We performed a hybrid capture‐2 technique to diagnose these samples on HPV and CT infection, and the women responded a questionnaire. Significant association was observed between nonstable marital status and hr‐HPV infection [OR = 2.61 (1.38–4.97) P = 0.003)], and age <25 years old [OR = 2.26 (1.09–4.71) P = 0.029]. Nonstable marital status was also associated with lr‐HPV infection [OR = 2.67 (1.59–4.50) P < 0.001), and age <25 years old [OR = 2.55 (1.51–4.32) P < 0.001). Fifty of the 371 pregnant women were infected with hr‐HPV (13.5%) and 111 (30.0%) were infected with lr‐HPV. The coinfections of HPV and CT were found in 31 women, that is, 8.36% of the pregnant women (P < 0.001). The high rate of simultaneous CT and HPV infection in pregnant women favors the recommendation to screen pregnant women for both CT and HPV. Diagn. Cytopathol. 2010.

Pero vaz de caminha : An interchange program for quality control between Brazil and Portugal

OBJECTIVE To start an interexchange program for quality control in cervical cytology and discuss conceptual criteria for diagnosis. STUDY DESIGN Slides were selected in the archives of the 2 institutes and included cases with unsatisfactory, negative and positive results. Sets of slides were changed between the partners every 3 months. At the end of each year a senior cytopathologist was invited to discuss the major discrepancies found in the study. RESULTS A total of 1,041 cases were analyzed. Full concordance was obtained in 74.4% (774) of cases and discrepancies in 25.6% (267 cases). Full agreement was achieved in 276 (39%) of 707 cases categorized as negative. In 421 negative cases from laboratory A, this concordance represents 65.5% and 96.5% for laboratory B, which submitted 286 negative cases. The main discordance was the high number of atypical squamous cells of undetermined significance cases: 3.1% for A and 128 (33.2%) for B. Samples with discrepancies related to the quality of the material was another controversial issue: of 16 cases from laboratory A, 6 (37.5%) unsatisfactory cases were the same and 10 (62.5%) different. Laboratory B presented 20 unsatisfactory cases, and 14 (70.0%) had other diagnoses. Low grade squamous intraepithelial lesion and high grade squamous intraepithelial lesion concordance ranged from 75% to 80%, and invasive carcinoma has 4 discordances (28.5%), 3 previously screened as high grade squamous intraepithelial lesion and 1 as atypical squamous cells of undetermined significance. The kappa value obtained was 0.65, indicating substantial agreement. CONCLUSION Our results indicated that atypical squamous cells of undetermined significance diagnoses are the crucial point of controversies and concern the quality of routine diagnosis in cytopathology.

Screening for cervical cancer in high-risk populations : DNA pap test or hybrid capture II test alone?

Summary: This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq® LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in São Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as “gold standard” and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.

Asociación entre la expresión génica de p16INK4A, la tríada de histidina frágil y las lesiones cervicales

Objetivo. Este estudio transversal tuvo como objetivo valorar la asociación entre el análisis inmunohistoquímico de p16INK4A y de la tríada de histidina frágil (FHIT) y la presencia de lesiones cervicales precancerosas. Material y métodos. Se estudió a mujeres visitadas en el Pérola Byington Hospital, Sao Paulo, Brasil, que presentaban una cervicitis confirmada histológicamente (n = 31), neoplasia cervical intraepitelial (CIN) 1 (n = 30), CIN 2,3 (n = 30) o cáncer cervical (n = 7), en las que se obtuvieron muestras de material cervical para citología líquida (CL), prueba del virus del papiloma humano Hybrid Capture 2 (HC2), y reacciones inmunohistoquímicas de p16 y de FHIT. Resultados. Las reacciones de p16 y de FHIT se valoraron de la siguiente forma: <1%, 1% a 5%, > 5% a 25%, y > 25%. Se utilizó un análisis de curva de receptor‐operador para elegir los valores de corte de p16 y FHIT para los ulteriores análisis de variables discretas. La totalidad de los 37 casos de CIN 2‐3/cáncer, excepto uno, presentaron una puntuación de p16 de la clase superior a 1% a 5%. De los 61 casos de cervicitis/CIN 1, 46 (75%) tenían una puntuación de p16 de la clase inferior a 1% a 5%. En cambio, no se observó asociación alguna de la expresión de FHIT con la gravedad de las lesiones cervicales en este conjunto de datos. Los análisis de la curva de operador‐receptor sugirieron la puntuación de 1% a 5% para p16 como valor de corte que mejor discrimina entre CIN 2‐3/cáncer y cervicitis/CIN 1. No pudo sugerirse ningún valor de corte para las puntuaciones de FHIT con esta serie de datos. Conclusión. La expresión de p16, pero no en cambio la de FHIT, tiene un potencial de uso como herramienta diagnóstica complementaria para el estudio de las lesiones cervicales inducidas por el virus del papiloma humano, si estos resultados son confirmados por estudios más amplios. ▪