Validation of Linear Range HER2/Estrogen Receptor/Progesterone Receptor IHControls for Daily Quality Assurance.

OBJECTIVES: To evaluate a new US Food and Drug Administration (FDA)-cleared immunohistochemistry (IHC) control (IHControls [Boston Cell Standards]) comprising peptide epitopes for HER2, estrogen receptor (ER), and progesterone receptor (PR) attached to cell-sized microspheres and to compare its performance against conventional tissue controls. METHODS: IHControls and tissue/cell line controls for HER2, ER, and PR were compared side by side daily at 5 clinical IHC laboratories for 1 to 2 months. Separately, the sensitivity of the 2 types of controls was evaluated in simulated IHC assay failure experiments by diluting the primary antibody. Additional evaluations included lot-to-lot manufacturing reproducibility of 3 independent lots and specificity against 26 antigenically irrelevant IHC stains. RESULTS: Side-by-side testing revealed a 99.6% concordance between IHControls and tissue controls across 5 IHC laboratories and 766 individual evaluations. Three discordant quality control events were the result of operator error. Simulated assay failure data showed that both IHControls and tissue controls are similarly capable of detecting IHC staining errors. Manufacturing reproducibility of IHControls showed less than 10% variability (coefficient of variation). No cross-reactions were detected from 26 antigenically irrelevant IHC stains. CONCLUSIONS: IHControls, the first FDA-cleared IHC controls, can sensitively and accurately detect IHC assay problems, similar to tissue controls.

Trophoblast damage with acute and chronic intervillositis: disruption of the placental barrier by severe acute respiratory syndrome coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was demonstrated in the placenta; however, the data on the prevalence of placental infection and associated histopathology are limited. To identify the frequency and features of SARS-CoV-2 involvement, we performed a clinicopathologic analysis of 75 placental cases from women infected at the time of delivery and 75 uninfected controls. Placental samples were studied with anti-SARS-CoV-2 immunohistochemistry and/or in situ hybridization. Positive results were confirmed by electron microscopy and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). During delivery, only one woman had symptoms of coronavirus disease 2019, six women reported previous symptoms, and 68 women were asymptomatic. All neonates tested negative for SARS-CoV-2 as per nasopharyngeal swab PCR results. Obstetric histories were unremarkable in 29 of 75 SARS-CoV-2-positive and 8 of 75 SARS-CoV-2-negative women. Placental examination was normal in 12 of 75 infected and 3 of 75 uninfected subjects, respectively. In the remaining cases, placental pathology correlated with obstetric comorbidities without significant differences between SARS-CoV-2-positive and SARS-CoV-2-negative women. SARS-CoV-2 was identified in one placenta of an infected, but asymptomatic, parturient. Viral staining was predominantly localized to the syncytiotrophoblast (STB) which demonstrated marked damage accompanied by perivillous fibrin deposition and mixed intervillositis. A significant decrease of viral titers was detected in the attached umbilical cord compared with the villous parenchyma as per qRT-PCR. SARS-CoV-2 is seldom identified in placentas of infected women. Placental involvement by the virus is characterized by STB damage disrupting the placental barrier and can be seen in asymptomatic mothers without evidence of vertical transmission.