Summary Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a ...semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called “Score the Core” (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers.
Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of ...aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD.
This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement.
Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27–0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15–0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing.
Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.
Summary Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) is a scaffolding protein that links cell adhesion molecules, receptors and signaling molecules to the ...cytoskeleton and maintains the architecture of cell junctions. MAGI-2 gene rearrangements have recently been described in prostate cancer. We studied the immunohistochemical expression of MAGI-2 protein in prostate tissue. Seventy-eight radical prostatectomies were used to construct three tissue microarrays consisting of 512 1-mm cores, including benign tissue, benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma, Gleason patterns 3-5. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and double stain MAGI-2/p63 was performed and analyzed by visual and image analysis, the latter as percent of analyzed area (%AREA), and mean optical density multiplied by %AREA (STAIN). By visual and image analysis MAGI-2 was significantly higher in adenocarcinoma and HGPIN compared to benign (benign vs. HGPIN p < 0.001; benign vs. adenocarcinoma, p < 0.001). HGPIN and adenocarcinoma did not significantly differ by either modality. Using visual intensity to distinguish benign and adenocarcinoma, a receiver/operator curve yielded an area under the curve of 0.902. A STAIN threshold of 1470 yielded a sensitivity of 0.66 and specificity of 0.96. There was a significant correlation between PTEN and MAGI-2 staining for normal and BPH, but this was lost in HGPIN and cancer. We conclude that MAGI-2 immunoreactivity is elevated in prostate cancer and HGPIN compared to normal, and suggest that MAGI-2 may contribute to prostate carcinogenesis. This is the first report of MAGI-2 staining by immunohistochemistry in prostate cancer.
