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Background: The National Comprehensive Cancer Network recommends that patients with hormone receptor-positive early breast cancer be considered for adjuvant endocrine therapy (ET) after primary treatment like surgical excision. Adjuvant chemotherapy (CT) use primarily depends on risk of recurrence. Biomarkers such as Ki-67 potentially have most value in patients with intermediate risk factors, such as involvement of 1–3 positive nodes. This study evaluated the use of Ki-67 testing and treatment patterns in patients with HR+, human epidermal growth factor receptor 2-negative early breast cancer. Methods: This was an observational retrospective cohort study of patients with electronic medical records from January 2010 to August 2018 treated for HR+, HER2− early breast cancer at Sarah Cannon sites in the United States (US). Overall, 567 patients were randomly selected after using the eligibility criteria: female or male ≥18 years, without distant metastases, and with available physician and pathology reports. Multivariable logistic regression was used to investigate factors predicting Ki-67 testing and test results. Descriptive analyses were applied to treatment patterns. Results: Multivariable logistic regression analyses found no clinical or pathological factors that predicted whether Ki-67 testing had been ordered by physicians. Of all tested patients (N = 130), having Grade-2 tumors (OR, 7.95 [95% CI: 2.05, 30.9]; p = 0.0027) or Grade-3 tumors (OR, 95.3 [95% CI, 11.9, 760.7]; p < 0.001) at initial diagnosis was a predictor of high Ki-67 expression (≥20%). Ki-67 expression was tested in 23.6% (61/258) of patients with 1–3 positive nodes; 54.1% of them (33/61) had high Ki-67 expression (≥20%). While having a higher grade tumor predicted high Ki-67 (≥20%), 28.6% of patients with Grade-1 tumors also had high Ki-67 expression. Neo-adjuvant therapy was received by 16.0% of patients (91/567), most of whom (66/91; 72.5%) received CT alone. Adjuvant therapy, either endocrine and/or chemotherapy, was received by 92.6% (525/567) of patients and by 67.0% (61/91) of those who received neo-adjuvant therapy. Most (428/525, 81.5%) received ET in the adjuvant treatment setting. Conclusions: High grade tumors predicted high Ki-67 (≥20%) expression, but Ki-67 testing was not widely used in these US patients. Most HR+, HER2− early breast cancers were treated with adjuvant ET, with or without CT. [ABSTRACT FROM AUTHOR]

The first biomarker-based cervical cancer screening test, p16/Ki-67 dual-stained cytology (DS), has been clinically validated and approved in the United States for triage of women being screened for cervical cancer who test positive for high-risk human papillomavirus (hrHPV). The primary aim of this work is to evaluate the cost-effectiveness of DS triage after co-testing findings of positive non-16/18 HPV types and atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions cytology. A payer-perspective Markov microsimulation model was developed to assess the impact of DS reflex testing. Each comparison simulated 12,250 screening-eligible women through health states defined by hrHPV status and genotype, cervical intraepithelial neoplasia grades 1-3, invasive cervical cancer (ICC) by stage, and cancer-related or non-cancer death. Screening test performance data were from the IMPACT clinical validation trial. Transition probabilities were from population and natural history studies. Costs of baseline medical care, screening visits, tests, procedures, and ICC were included. DS reflex after co-testing was cost-effective with incremental cost-effectiveness ratios per quality-adjusted life-year gained of $15,231 [95% confidence interval (CI), $10,717-$25,400] compared with co-testing with hrHPV pooled primary and genotyped reflex testing, and $23,487 (95% CI, $15,745-$46,175) compared with co-testing with hrHPV genotyping with no reflex test. Screening and medical costs and life-years increased, while ICC costs and risk of ICC death decreased. Incorporating DS reflex into co-testing cervical cancer screening algorithms is projected to be cost-effective., Prevention Relevance: The p16/Ki-67 dual-stained cytology (DS) test was recently approved in the United States as a reflex test for cervical cancer screening following positive high-risk human papillomavirus (hrHPV) test results. Adding DS reflex to hrHPV and cervical cytology co-testing strategies in the United States is expected to be cost-effective per life-year or quality-adjusted life-year gained., (©2023 The Authors; Published by the American Association for Cancer Research.)

The objective of this study was to measure concordance of results obtained from the US Food and Drug Administration-approved Ki-67 immunohistochemistry MIB-1 pharmDx assay performed on the Dako Omnis automated staining instrument (Omnis) versus results produced from the assay reagents applied using an optimized protocol on the more widely available Autostainer Link 48 (ASL48) platform. Tissue sections obtained from 40 formalin-fixed paraffin-embedded breast carcinoma samples, with available Oncotype DX Breast Recurrence Score (RS) results, were stained. Three certified pathologists scored slides at 3 timepoints, totaling 360 observations for each instrument (N=720 total) using the approved scoring approach. Using the ≥20% cutoff, agreement was calculated with corresponding 2-sided 95% percentile bootstrap confidence intervals (CIs). Pairwise comparisons (N=360) from the interinstrument evaluation, performed with all observers, resulted in 325 (90.3%) concordant outcomes (244 negative and 81 positive) and 35 (9.7%) discordant outcomes. The overall agreement was 90.3% (95% confidence interval, 85.6% to 94.4%). No significant systematic differences were observed between instruments. Specimens scored from the Omnis were on average <1% higher than ASL48, with high correlation and little bias between the continuous Ki-67 scores (concordance correlation coefficient=0.916). Most specimens with a Ki-67 score ≥20% had a RS >25. This study demonstrated that good concordance can be achieved with the reagents run on the ASL48 instrument when using an optimized protocol and standardized scoring., Competing Interests: M.K. reports receiving lecture fees from Agilent Technologies and has no additional potential conflicts of interest to disclose. E.D.-K. served on an oncology advisory board for Eli Lilly and Company. F.S. is an employee and company stockholder at Eli Lilly and Company. S.R.W. is an employee and company stockholder at Eli Lilly and Company. A.M.G. is an employee and company stockholder at Eli Lilly and Company; he also reports his spouse is an employee of Eli Lilly and Company. S.S.B. has received grant or research support from Agilent Technologies and is a paid speaker for Agilent Technologies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Protein expression of p63 is used to differentiate prostate cancer from benign mimickers. Recent studies suggest that it may also distinguish aggressive prostate cancer with down-regulated expression occurring in men with more advanced disease. We conducted a prospective study among 298 men ages 51 to 84 years who were diagnosed with prostate cancer in the Physicians' Health Study in 1983 to 2004 and whose tissue was available for immunohistochemical staining. We used Cox proportional hazards regression to evaluate the association of p63 protein expression with fatal prostate cancer. We correlated p63 expression with tumor cell proliferation (Ki-67) and apoptosis (TUNEL staining). The predominant location of tumor p63 staining occurred in the cytoplasm, an uncommon departure from the strong nuclear staining usually observed in nonneoplastic basal cells. Increasing expression of cytoplasmic p63 (tertiles) was associated with prostate cancer mortality (n = 19 deaths); the hazard ratios (95% confidence intervals) were 1.0 (reference), 4.0 (0.9-18.9), and 5.9 (1.3-27.5; P(trend) = 0.03). The positive trend remained significant (P = 0.047) after multivariable adjustment for age, year of diagnosis, and Gleason score. Higher tertiles of cytoplasmic p63 were also associated with reduced levels of apoptosis (P(trend) = 0.0408) and increased cellular proliferation (P(trend) = 0.0026). We found aberrant expression of p63 in the cytoplasm to be associated with increased prostate cancer-specific mortality up to 20 years after diagnosis. The mislocalized expression was associated with reduced apoptosis and higher proliferative activity and may suggest an oncogenic role in prostate cancer progression and survival.

To evaluate the NIH Image measured MIB-1 staining index (SI) as a useful tool for the determination of proliferative activity of gliomas, MIB-1 immunohistochemistry was performed on paraffin sections to estimate the proliferative activity of 50 gliomas. Five to eight RGB images at 200 magnifications were acquired per sample in a Macintosh computer using a RD-175 digital camera and Adope Photoshop program, followed by conversion of the RGB image to B (blue subtracted) and R (red subtracted) images and finally automatic cell counting of more than 1000 cells per sample by the NIH Image analysis program. The mean MIB-1 staining indices by both NIH count and visually assessed (manual) count respectively were 12.7% +/- 9.9% (mean +/- standard deviation) and 12.6% +/- 9.9% in all gliomas (n = 50), 2.9% +/- 0.6% and 2.3% +/- 0.6% in grade I and II astrocytomas (n = 9), 10.7% +/- 8.9% and 11.1% +/- 9.0% in grade III gliomas (n = 17), 16.1% +/- 9.1% and 16.3% +/- 9.1% in glioblastoma multiformes (n = 20), 26.0% +/- 4.9% and 24.5% +/- 2.6% in other glial tumors (n = 4). These paired values were assumed to be identical, since the p value obtained by paired t-test in all gliomas was 0.905. We conclude that the MIB-1 staining index measured by NIH Image is reliable and universal.