Immunohistochemical assessment of HER2 low breast cancer: interobserver reproducibility and correlation with digital image analysis.

PURPOSE: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC. METHODS: Fifty whole-slide biopsies of BC with HER2 IHC staining were evaluated, comprising 25 cases originally reported as IHC score 0 and 25 as 1 +. These slides were digitally scanned. Six pathologists with breast expertise independently reviewed and scored the scanned images, and DIA was applied. Agreement among pathologists and concordance between pathologist scores and DIA results were statistically analyzed using Kendall coefficient of concordance (W) tests. RESULTS: Substantial agreement among at least five of the six pathologists was found for 18 of the score 0 cases (72%) and 15 of the score 1 + cases (60%), indicating excellent interobserver agreement (W = 0.828). DIA scores were highly concordant with pathologist scores in 96% of cases (47/49), indicating excellent concordance (W = 0.959). CONCLUSION: Although breast subspecialty pathologists were relatively consistent in evaluating BC with HER2 IHC scores of 0 and 1 +, DIA may be a reliable supplementary tool to enhance the standardization and quantification of HER2 IHC assessment, especially in challenging cases where results may be ambiguous (i.e., scores 0-1 +). These findings hold promise for improving the accuracy and consistency of HER2 testing.

Effect of a new desensitizing material on human dentin permeability.

OBJECTIVES: Resin-modified glass ionomers (RMGI) have demonstrated clinical success providing immediate and long-term relief from root sensitivity. RMGIs have been recently introduced as paste-liquid systems for convenience of clinical usage. The objective of this study was to measure the ability of a new paste-liquid RMGI to reduce fluid flow through human dentin, compared to an established single-bottle nanofilled total etch resin adhesive indicated for root desensitization. METHODS: Dentin permeability was measured on human crown sections on etched dentin, presenting a model for the exposed tubules typical of root sensitivity, and permitting measurement of the maximum permeability. In the first two groups, the etched dentin was coated with either the RMGI or adhesive, and permeability measured on the coated dentin. In a third group, a smear layer was created on the dentin with sandpaper, then the specimens were coated with the RMGI; permeability was measured on the smeared and coated dentin. Specimens from each group were sectioned and examined via scanning electron microscopy (SEM). RESULTS: Both the resin adhesive and the new paste-liquid RMGI protective material significantly reduced fluid flow through dentin, and exhibited excellent seal on dentin with either open tubules or smear-layer occluded tubules. The RMGI infiltrated the smear layer with resin during placement, penetrated dentin tubules, and formed resin tags. SIGNIFICANCE: The RMGI was equivalent to the adhesive in its ability to reduce fluid flow and seal dentin. It is therefore concluded that the new RMGI and the adhesive show the potential to offer excellent sensitivity relief on exposed root dentin.

Effect of a new liner/base on human dentin permeability.

OBJECTIVES: Resin-modified glass ionomers (RMGI) have demonstrated clinical success in their ability to minimize post-operative sensitivity of restorations. RMGIs have been recently introduced as paste-liquid systems for convenience of clinical usage. The objective of this study was to measure the ability of a new paste-liquid RMGI liner/base to reduce fluid flow through human dentin. METHODS: Dentin permeability was measured on human crown sections on etched dentin, using etched dentin as a model for the exposed tubules typical of root sensitivity, and permitting measurement of the maximum permeability. In the one group, the etched dentin was coated with the RMGI, and pre- and post-treatment permeability was measured on the coated dentin. In the second group, a smear layer was created on the dentin with sandpaper, then the samples were coated with the RMGI; permeability was measured on the smeared and coated dentin. Samples from each group were sectioned and examined via scanning electron microscopy (SEM). RESULTS: The new paste-liquid RMGI liner/base significantly reduced fluid flow through dentin, and exhibited excellent seal on dentin with either a smear layer or open tubules. SEM images show evidence that the RMGI infiltrated the smear layer with resin during placement, penetrated dentin tubules, and formed resin tags in acid-etched dentin. CONCLUSIONS: Based on these results, combined with previous research on adhesion and microleakage, it is concluded that the new RMGI liner/base should minimize post-operative sensitivity in restorations.

Effects of residual ethanol on the rate and degree of conversion of five experimental resins.

OBJECTIVES: This study examined the extent of ethanol retention in five comonomer blends of experimental methacrylate-based dental adhesives, containing (10, 20, or 30 wt.%) ethanol, after solvent evaporation, as well as observing the effect of residual ethanol and exposure duration on degree of conversion (DC). The null hypothesis that was tested was that residual, unevaporated ethanol has no effect on the rate or extent of DC of polymerized adhesive resins. METHODS: A known mass of each mixture was placed in glass wells and evaporated for 60s. The mass of the mixtures before and after evaporation was measured, allowing calculation of the gravimetric ethanol loss/retention. RESULTS: The concentration of retained ethanol increased significantly with ethanol concentration (p<0.01): 1.1-1.9 mole/L for 10% ethanol/90% comonomers, 2.2-3.5 mole/L for 20% ethanol, and 2.6-3.7 mole/L for 30% ethanol/70% comonomers. As ethanol is evaporated from solvated comonomer mixtures, the molar concentration of comonomers increases, reducing the vapor pressure of the remaining ethanol. Thus, the fractional loss of ethanol solvent decreases as the comonomer concentration increases. The DC of 10, 20, and 30 wt.% ethanol blends increased with ethanol concentration in four of the five experimental resins (p<0.05), increasing by 30-45% when 10 or 20 wt.% ethanol was added to neat resins, regardless of exposure duration. Depending on the resin system, inclusion of 30% ethanol lowered DC at 20s but increased DC after 40-60s of light exposure. SIGNIFICANCE: Since 10 and 20 wt.% ethanol-resin blends increased the DC of solvated resins by 30-45% over neat resins, the test null hypothesis is rejected. Even with prolonged evaporation, 4-9% residual ethanol concentration can remain in 90/10 (wt./wt.) comonomer-ethanol mixtures. This is thought to be because comonomers lower the vapor pressure of ethanol. This amount of residual ethanol facilitates DC but lowers the rate of polymerization.