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BACKGROUND The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. METHODS ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. RESULTS In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. CONCLUSIONS The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.

Prostate cancer (PC) development reflects a complex sequence of biologic and molecular events. Several inheritable and somatic genetic changes have been identified. The knowledge of the molecular basis of PC can improve our understanding of the causes of this common cancer and provide information on prognosis and treatment. To date, however, no molecular studies have yet yielded consistent information that is ready to be incorporated into clinical practice. We reviewed the current literature on the molecular biology of prostate cancer and analyzed different potential tumor markers according to the classical concepts of oncogenes, suppressor genes, and the more modern concepts of genes involved in detoxification or inflammatory pathways of cancer progression. This review aims to identify trends in PC research and suggests potential clinical applications for diagnosis, prognosis, prevention and treatment.

Digital imaging, including the use of artificial intelligence, has been increasingly applied to investigate the placenta and its related pathology. However, there has been no comprehensive review of this body of work to date. The aim of this study was to therefore review the literature regarding digital pathology of the placenta. A systematic literature search was conducted in several electronic databases. Studies involving the application of digital imaging and artificial intelligence techniques to human placental samples were retrieved and analyzed. Relevant articles were categorized by digital image technique and their relevance to studying normal and diseased placenta. Of 2008 retrieved articles, 279 were included. Digital imaging research related to the placenta was often coupled with immunohistochemistry, confocal microscopy, 3D reconstruction, and/or deep learning algorithms. By significantly increasing pathologists’ ability to recognize potentially prognostic relevant features and by lessening inter-observer variability, published data overall indicate that the application of digital pathology to placental and perinatal diseases, along with clinical and radiology correlation, has great potential to improve fetal and maternal health care including the selection of targeted therapy in high-risk pregnancy.

To determine the genetic differences/similarities in ampulla of Vater cancers (AVC) with respect to other pancreatic tumor types. We analyzed eight cases of primary AVC by genome-wide allelotyping on DNA obtained from frozen tissue. A total of 372 microsatellite loci were used for each case, for a total of 2,976 microsatellites analyzed. Of the 2,159 informative markers, 400 were allelic losses and 1,759 markers were retained for an average fractional allelic loss of 0.19. Seven cases showed LOH on at least two markers on chromosomal arm 11p, while six cases showed allelic losses on 11q. The high frequency of LOH on chromosome 11 was also confirmed by analysis of an additional 17 paraffin-embedded AVC. Frequent LOH (50% or greater) was also found on chromosome arms 5q, 6q, 9p, 13, 16p, 17p, and 18p. It can be inferred that the targets of inactivation on chromosomes 5q, 9p, and 17p appear to be APC, p16, and p53, respectively, while the critical target(s) of inactivation at the other frequently lost loci remain to be characterized. The resulting allelotype reveals that distinctive chromosomal alterations are present in these neoplasms, indicating that it is a tumor entity distinct from pancreatic adenocarcinoma.