Hammond, M. Elizabeth H.

Abstract Context. —Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. Objectives. —To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. Design. —We convened an expert panel to discuss HER2 gene amplification testing by fluorescence in situ hybridization. Components addressed included a definition of HER2 amplification heterogeneity, practice guidelines for examination of the tissue, and reporting criteria for this analysis. Results. —Genetic heterogeneity for amplification of HER2 gene status in invasive breast cancer is defined and guidelines established for assessing and reporting HER2 results in these cases. These guidelines are additive to and expand those published in 2007 by the American Society of Clinical Oncology and the College of American Pathologists. Conclusion. —Standardized methods for analysis will improve the accuracy and consistency of interpretation of HER2 gene amplification status in breast cancer.

Abstract Context. —The American Board of Medical Specialties Maintenance of Certification (MOC) process will become effective in 2006. The College of American Pathologists (CAP) Education Committee defined pathology-specific competencies within MOC categories and used data from a survey of pathologists to create education courses targeted to each MOC category. Objective. —To define pathology-specific competencies within MOC categories and to identify priority learning needs for pathologists. Design. —A 5-step process was completed for defining pathology-specific competencies within MOC categories and creating education courses targeted to competencies identified in each MOC category. A random survey was distributed to identify priority learning needs based on the gap between the importance rating of each knowledge and skill statement and a rating of current level of proficiency in 3 areas. Results. —Specific competencies and knowledge and skill statements were identified for each MOC competency category. Findings indicate pathologists believe they are poorly prepared for practice in competency categories related to systems-based practice and practice-based learning and improvement. Conclusions. —The CAP has focused education efforts on identifying a process for defining and responding to the MOC challenge. Pathologists have told us that they have significant needs for learning in specified areas and the CAP will focus development of education courses to meet those identified needs.

Abstract Context. —Inferences from tumor marker studies are complicated by a variety of statistical concerns, which can make proper interpretation of results difficult. This article focuses on important issues that should be addressed when designing, conducting, and analyzing tumor marker studies. Objective. —To highlight the importance of considering statistical significance, risk ratios, statistical power, reproducibility, multiple testing, confirmatory studies, and missing data in the design of marker studies used for prognosis. Results. —Suggestions are provided for more effectively conducting marker studies. These include more careful attention to adequacy of the number of subjects for a marker study and improved documentation and standardization of assay methods. The importance of complete reporting of study results and description of the statistical analysis methods used is also emphasized. Conclusion. —Cooperation among clinicians, laboratory scientists, and statisticians will be required to conduct statistically sound tumor marker studies and to facilitate prioritizing markers for new and confirmatory studies in an environment of limited patient and specimen resources.