José Humberto Fregnani

Evaluation of Elafin Immunohistochemical Expression as Marker of Cervical Cancer Severity

<b><i>Introduction:</i></b> The main risk factor for the development of cervical cancer (CC) is persistent infection by human papillomavirus (HPV) oncogenic types. In order to persist, HPV exhibits a plethora of immune evasion mechanisms. PI3/Elafin (Peptidase Inhibitor 3) is an endogenous serine protease inhibitor involved in epithelial protection against pathogens. PI3/Elafin’s role in CC is still poorly understood. <b><i>Materials and Methods:</i></b> In the present study, we addressed PI3/Elafin protein detection in 123 CC samples by immunohistochemistry and mRNA expression in several datasets available at Gene Expression Omnibus and The Cancer Genome Atlas platforms. <b><i>Results:</i></b> We observed that PI3/Elafin is consistently downregulated in CC samples when compared to normal tissue. Most of PI3/Elafin-positive samples exhibited this protein at the plasma membrane. Besides, high PI3/Elafin expression at the cellular membrane was more frequent in in situ stages I + II than in invasive cervical tumor stages III + IV. This indicates that PI3/Elafin expression is gradually lost during the CC progression. Of note, advanced stages of CC were more frequently associated with a more intense PI3/Elafin reaction in the nuclei and cytoplasm. <b><i>Conclusion:</i></b> Our results suggest that PI3/Elafin levels and subcellular localization may be used as a biomarker for CC severity.

DNA Recovery Using Ethanol-Based Liquid Medium from FTA Card-Stored Samples for HPV Detection

<b><i>Introduction:</i></b> Alternative methods of dry storage and transportation may be a viable alternative to the use of liquid storage medium for cervical samples, especially for screening programs in places with few resources. <b><i>Objective:</i></b> The objective of this study is to verify the viability and efficacy of human papillomavirus DNA (HPV-DNA) detection in cervical cell samples collected and stored on a Flinders Technology Associates (FTA) card (Whatman Indicating FTA<sup>®</sup> Elute Micro Card) and subsequently recovered in ethanol-based liquid medium and to compare the results to those obtained using samples stored directly in ethanol-based liquid medium. <b><i>Study Design:</i></b> Thirty-four women submitted to ETZ (excision of the transformation zone of the cervix) were included in this study. Before ETZ, 2 samples of exfoliated cervical cells were collected from each woman by a doctor and stored in ethanol-based liquid medium and on an FTA card. DNA recovery from FTA samples was performed using ethanol-based liquid medium. Detection of HPV-DNA in the samples was performed using the Cobas® 4800 HPV Test Platform. <b><i>Results and Conclusions:</i></b> The HPV-DNA detection positivity rates were 70.6% for the samples collected directly in liquid medium and 64.7% for the samples stored on the FTA card, with high detection accuracy in the DNA samples recovered from the FTA card (area under the curve = 0.958; 95% confidence interval = 0.890–1.000). The concordance between the results obtained using the 2 storage media was 94.1% (Kappa = 0.866). These preliminary results suggest that collection of cervical material on an FTA card may be an alternative to storage in liquid medium since the liquid medium has some limitations. In addition, DNA recovery from the card using ethanol-based liquid medium streamlines the workflow in the laboratory and reduces the cost associated with reagents, thereby facilitating access to the HPV test in places with few resources and potentially improving cervical cancer screening.

Cancer inequalities in incidence and mortality in the State of São Paulo, Brazil 2001–17

AbstractBackgroundCancer disparities exist between and within countries; we sought to compare cancer‐specific incidence and mortality according to area‐level socioeconomic status (SES) in the State of São Paulo, Brazil.MethodsCancer cases diagnosed 2003–2017 in the Barretos region and 2001–2015 in the municipality of São Paulo were obtained from the respective cancer registries. Corresponding cancer deaths were obtained from a Brazilian public government database. Age‐standardized rates for all cancer combined and the six most common cancers were calculated by SES quartiles.ResultsThere were 14,628 cancer cases and 7513 cancer deaths in Barretos, and 472,712 corresponding cases and 194,705 deaths in São Paulo. A clear SES‐cancer gradient was seen in São Paulo, with rates varying from 188.4 to 333.1 in low to high SES areas, respectively. There was a lesser social gradient for mortality, with rates in low to high SES areas ranging from 86.4 to 98.0 in Barretos, and from 99.2 to 100.1 in São Paulo. The magnitude of the incidence rates rose markedly with increasing SES in São Paulo city for colorectal, lung, female breast, and prostate cancer. Conversely, both cervical cancer incidence and mortality rose with lower levels of SES in both regions.ConclusionsA clear SES association was seen for cancers of the prostate, female breast, colorectum, and lung for São Paulo. This study offers a better understanding of the cancer incidence and mortality profile according to SES within a highly populated Brazilian state.