Assessing the Reliability and Positive Predictive Value of p16 as a Surrogate for Human Papillomavirus-Mediated E6/7 mRNA Expression in Squamous Cell Carcinoma of the Anal Canal.

BACKGROUND: Human papillomavirus has been implicated in the carcinogenesis of squamous cell carcinoma of the anal canal. p16 expression and the presence of human papillomavirus DNA have been used to define human papillomavirus-positive patients, but neither approach has been validated against the standard of human papillomavirus E6/7 mRNA expression at this disease site. OBJECTIVE: This study aimed to evaluate the acceptability of p16 immunohistochemistry as a surrogate to E6/7 mRNA expression in identifying human papillomavirus-mediated squamous cell carcinoma of the anal canal. DESIGN: This was a retrospective analysis of a previously constructed tissue microarray. SETTINGS: This study was conducted at a tertiary academic center. PATIENTS: Biopsies and resection specimens from patients diagnosed with squamous cell carcinoma of the anal canal at the study institution from 2005 to 2015 were reviewed for sample adequacy. MAIN OUTCOME MEASURES: Concordance between p16 positivity by immunohistochemistry and E6/7 mRNA expression by in situ hybridization was evaluated. Sensitivity, specificity, and positive predictive value were assessed. RESULTS: Among the 25 patients evaluated, p16 and E6/7 mRNA results were concordant in 24 of 25 specimens (96%). Of the 24 concordant samples, there were 23 true positives (p16+ and E6/7+) and 1 true negative (p16- and E6/7-). One specimen was discordant (p16- and E6/7+) between p16 and E6/7 mRNA (4%). This resulted in a sensitivity of 96% and a specificity of 100%. Positive predictive value of p16 immunohistochemistry for E6/7 mRNA expression was 100%. LIMITATIONS: This study was limited by its retrospective nature and small sample size. It only assessed diagnostic parameters rather than prognostic implications. CONCLUSIONS: In this study, the clinically prevalent method of p16 immunohistochemistry showed excellent concordance with the standard of E6/7 mRNA expression and demonstrated its potential to serve as a surrogate for identifying human papillomavirus-induced squamous cell carcinoma of the anal canal. See Video Abstract at http://links.lww.com/DCR/B448. EVALUANDO LA CONFIABILIDAD Y EL VALOR PREDICTIVO POSITIVO DE P, COMO SUSTITUTO DE LA EXPRESIN DE ARNM DE E / , MEDIADA POR EL VIRUS DEL PAPILOMA HUMANO, EN CARCINOMA DE CLULAS ESCAMOSAS DEL CANAL ANAL: ANTECEDENTES:El virus del papiloma humano se ha relacionado en la carcinogénesis del carcinoma de células escamosas del canal anal. La expresión de p16 y la presencia de ADN del virus del papiloma humano, se han utilizado para definir a los pacientes positivos al virus del papiloma humano. Pero ninguno de estos enfoques, han sido validados frente al estándar de oro de la expresión del ARNm del virus del papiloma humano E6 / 7, en este sitio de la enfermedad.OBJETIVO:El estudio tuvo como objetivo, evaluar la aceptabilidad de la inmunohistoquímica del p16, como sustituto de la expresión de ARNm de E6 / 7, en la identificación del carcinoma de células escamosas del canal anal, mediada por virus del papiloma humano.DISEÑO:Fue un análisis retrospectivo de un microarreglo de tejido previamente construido.AJUSTE:El estudio se realizó en un centro académico terciario.PACIENTES:Se revisaron biopsias y muestras de resección de pacientes diagnosticados con carcinoma de células escamosas del canal anal, en la institución del estudio, entre 2005 y 2015 para determinar la idoneidad de la muestra.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluó la concordancia entre la positividad de p16 por inmunohistoquímica y la expresión de ARNm de E6 / 7 por hibridación in situ. Se evaluaron la sensibilidad, especificidad y valor predictivo positivo.RESULTADOS:Entre los 25 pacientes evaluados, los resultados del ARNm de p16 y E6 / 7 fueron concordantes en 24/25 muestras (96%). De las 24 muestras concordantes, hubo 23 positivos verdaderos (p16 + y E6 / 7 +) y un negativo verdadero (p16- y E6 / 7-). Una muestra fue discordante (p16- y E6 / 7 +) entre p16 y ARNm de E6 / 7 (4%). Esto resultó en una sensibilidad del 96% y una especificidad del 100%. El valor predictivo positivo de la inmunohistoquímica de p16 para la expresión de ARNm de E6 / 7 fue del 100%.LIMITACIONES:El estudio estuvo limitado por su naturaleza retrospectiva y por el tamaño pequeño de la muestra. Solamente evaluó los parámetros de diagnóstico, en lugar de las implicaciones pronosticas.CONCLUSIONES:En este estudio, el método clínico prevalente de inmunohistoquímica p16, mostró una excelente concordancia con el estándar de oro de la expresión de ARNm de E6 / 7 y demostró su potencial para servir, como sustituto para identificar el carcinoma de células escamosas del canal anal, inducido por el virus del papiloma humano. Consulte Video Resumen en http://links.lww.com/DCR/B448.

Methanol Detected in a Subdural Hematoma as an Embalming Artifact.

Analysis of subdural hematomata has been used to suggest antemortem drug concentrations, with the assumption that materials within the hematoma are less subject to metabolism or degradation during any survival period and postmortem interval. We report the case of an 87-year-old woman whose death had not been reported to the coroner's office until postembalming. Autopsy revealed a traumatic brain injury with subdural hematoma causing a mass effect. Testing of the clot indicated a methanol concentration of 51.8 mg%. No additional analyses were detected. These findings suggest that methanol can be present in a postmortem hematoma sample, yet not represent a poisoning. Our findings also suggest that while the interior of hematomata do not necessarily represent completely "protected space" from postmortem diffusion of some blood constituents, such diffusion is not facile, and analysis may still provide useful indications of antemortem drugs present, if not actual concentrations.

Previously Unreported Complication of Coronary Artery Bypass Grafting: Suture Rupture Resulting in Patient's Death.

Traditionally, the manner of death in most hospital autopsy cases is natural, in which death is due to the natural course of disease or reasonably anticipated outcomes of medical interventions. Some cases fall into a potential gray zone between natural and accident, including rare or unanticipated outcomes of medical interventions. We present a case of a patient postcoronary artery bypass graft. Autopsy revealed the proximal anastomosis of the aorta-to-first-diagonal-coronary-artery-to-second-obtuse-marginal-artery graft was detached from the aorta. A broken suture was present at the disconnected anastomosis, with intact knots but was broken along its length. In-hospital mortality rates of CABG range from 1% to 3%, with several autopsy studies identifying surgical complications as the cause of death in one-third of perioperative deaths. No publications were found that described suture rupture as directly relating to the cause of death. This case report describes a previously unreported complication of coronary artery bypass grafting.