Search

Genomic biomarker testing has grown dramatically in recent years, from single-gene testing to larger panels with hundreds of genes or even the entire exome and genome. (1) Beyond individual mutations, [...], * Context.-Biomarker reporting has increasingly become a key component of pathology reporting, providing diagnostic, prognostic, and actionable therapeutic data for patient care. Objective.-To expand and improve the College of American Pathologists (CAP) biomarker protocols. Design.-We surveyed CAP members to better understand the limitations they experienced when reporting cancer biomarker results. A Biomarker Workgroup reviewed the survey results and developed a strategy to improve and standardize biomarker reporting. Drafts of new and revised biomarker protocols were reviewed in both print and electronic template formats during interactive webinars presented to the CAP House of Delegates. Feedback was collected, and appropriate revisions were made to finalize the protocols. Results.-The first phase of the CAP Biomarker Workgroup saw the development of (1) a new stand-alone general Immunohistochemistry Biomarker Protocol that includes reporting for ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER2 (human epidermal growth factor receptor 2), PD-L1 (programmed death ligand-1), and mismatch repair; (2) a new Head and Neck Biomarker Protocol that updates the prior 2017 paper-only version into an electronic template, adding new diagnostic and theranostic markers; (3) a major revision to the Lung Biomarker Protocol to streamline it and add in pan-cancer markers; and (4) a revision to the Colon and Rectum Biomarker Protocol to add HER2 reporting. Conclusions.-We have taken a multipronged approach to improving biomarker reporting in the CAP cancer protocols. We continue to review current biomarker reporting protocols to reduce and eliminate unnecessary methodologic details and update with new markers as needed. The biomarker templates will serve as standardized modular units that can be inserted into cancer-reporting protocols. (Arch Pathol Lab Med. 2024;148:1105-1109; doi: 10.5858/arpa.2023-0235-CP)

In 2014, the Pathology and Laboratory Quality Center for Evidence-Based Guidelines ('The Center') of the College of American Pathologists (CAP) published a clinical practice guideline that created recommendations for analytic [...], * Context.--In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered. Per the National Academy of Medicine standards for developing trustworthy guidelines, guidelines should be updated when new evidence suggests modifications. Objective.--To assess evidence published since the release of the original guideline and develop updated evidence-based recommendations. Design.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and update the original guideline recommendations using the Grading of Recommendations Assessment, Development and Evaluation approach. Results.--Two strong recommendations, 1 conditional recommendation, and 12 good practice statements are offered in this updated guideline. They address analytic validation or verification of predictive and nonpredictive assays, and recommended revalidation procedures following changes in assay conditions. Conclusions.--While many of the original guideline statements remain similar, new recommendations address analytic validation of assays with distinct scoring systems, such as programmed death receptor-1 and analytic verification of US Food and Drug Administration approved/ cleared assays; more specific guidance is offered for validating immunohistochemistry performed on cytology specimens. (Arch Pathol Lab Med. 2024;148:e111-e153; doi: 10.5858/arpa.2023-0483-CP

INTRODUCTION First released in 2010, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) estrogen receptor (ER) and progesterone receptor (PgR) testing guideline is aimed at improving the [...], * Purpose.--To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. Methods.--A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. Recommendations.--The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines. (Arch Pathol Lab Med. 2020;144:545-563; doi: 10.5858/arpa.2019-0904-SA)

The United States Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) established minimum requirements for assuring the quality of laboratory testing in US clinical laboratories. (1) To ensure accurate diagnosis [...], * Context.--To date, the College of American Pathologists (CAP) has developed 17 laboratory practice guidelines (LPGs) including updates. In 2013, the CAP was awarded a 5-year cooperative agreement grant from the United States Centers for Disease Control and Prevention to increase the effectiveness of LPGs. Objective.--To assess the awareness and adoption of 2 CAP LPGs: immunohistochemical (IHC) assay validation and initial workup of acute leukemia. Design.--Baseline surveys for each LPG were conducted in 2010 and 2015, respectively. To measure the adoption of guideline recommendations and inform future updates, a follow-up study consisting of surveys, telephone interviews, and focus group sessions was conducted in laboratories that indicated they perform IHC testing. A follow-up study for the acute leukemia LPG is planned. Results.--For the IHC Validation LPG, a total of 1624 survey responses, 40 telephone interviews, and discussions with 5 focus group participants were analyzed. The response rate for the aforementioned 3 modalities was 46%, 13%, and 3%, respectively. All modalities indicated most respondents were aware of the LPG and had adopted most or all of its recommendations. Respondents expressed needs for continued communication, increased specificity, and more prescriptive recommendations when the guideline is updated. Conclusions.--While data-driven development of evidence-based LPGs requires significant resources, active data collection to identify gaps and assess adoption contributes to improved laboratory testing practices in support of patient care. The CAP identified sustainable modalities to track metrics and developed multiple tools that should improve guideline development, adoption, and implementation. Of these modalities, written or electronic surveys were the most logistically feasible and had the highest response rate. (Arch Pathol Lab Med. 2020;144:83-89; doi: 10.5858/arpa.2018-0276-CP)

To the Editor. -- The recent editorial by Erik Thunnissen, 'How to Validate Predictive Immunohistochemistry Testing in Pathology? A Practical Approach Exploiting the Heterogeneity of Programmed Death Ligand-1 Present in [...]

First released in 2007 and updated in 2013, the recommendations by the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing [...], * Purpose.--To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline.Methods.--Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations.Recommendations.--Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not 'must') be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 (HER2/chromosome enumeration probe 17 [CEP17] ratio [greater than or equal to] 2.0; average HER2 copy number (Arch Pathol Lab Med. 2018;142:1364-1382; doi: 10.5858/arpa.2018-0902-SA)

The College of American Pathologists (CAP) Pathology and Laboratory Quality Center (the CAP Center) develops and maintains evidence-based laboratory practice guidelines (LPGs) that follow the US Institute of Medicine's Clinical [...], Context.--Laboratories must demonstrate analytic validity before any test can be used clinically, but studies have shown inconsistent practices in immunohistochemical assay validation. Objective.--To assess changes in immunohistochemistry analytic validation practices after publication of an evidence-based laboratory practice guideline. Design.--A survey on current immunohistochemistry assay validation practices and on the awareness and adoption of a recently published guideline was sent to subscribers enrolled in one of 3 relevant College of American Pathologists proficiency testing programs and to additional nonsubscribing laboratories that perform immunohistochemical testing. The results were compared with an earlier survey of validation practices. Results.--Analysis was based on responses from 1085 laboratories that perform immunohistochemical staining. Of 1057 responses, 65.4% (691) were aware of the guideline recommendations before this survey was sent and 79.9% (550 of 688) of those have already adopted some or all of the recommendations. Compared with the 2010 survey, a significant number of laboratories now have written validation procedures for both predictive and nonpredictive marker assays and specifications for the minimum numbers of cases needed for validation. There was also significant improvement in compliance with validation requirements, with 99% (100 of 102) having validated their most recently introduced predictive marker assay, compared with 74.9% (326 of 435) in 2010. The difficulty in finding validation cases for rare antigens and resource limitations were cited as the biggest challenges in implementing the guideline. Conclusions.--Dissemination of the 2014 evidencebased guideline validation practices had a positive impact on laboratory performance; some or all of the recommendations have been adopted by nearly 80% of respondents. (Arch Pathol Lab Med. 2017;141:1247-1254; doi: 10.5858/arpa.2016-0558-CP)

The College of American Pathologists (CAP) made a strategic decision 10 years ago to develop and publish evidence-based laboratory practice guidelines (LPGs). As the CAP had worked previously with the [...]

The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) HER2 testing guideline for breast cancer published in 2007 (1) was the first evidence-based guideline that directly addressed the [...]

The cancer protocols developed and maintained by the College of American Pathologists (CAP) have become de facto clinical guidelines for the appropriate reporting of pathologic features necessary for the treatment [...]

In 2015, the College of American Pathologists (CAP) conducted a survey of laboratory practices to examine the current state of immunohistochemical assay (IHC) validation procedures, assess general awareness of the [...], Context.--A cooperative agreement between the College of American Pathologists (CAP) and the United States Centers for Disease Control and Prevention was undertaken to measure laboratories&apos; awareness and implementation of an evidence-based laboratory practice guideline (LPG) on immunohistochemical (IHC) validation practices published in 2014. Objective.--To establish new benchmark data on IHC laboratory practices. Design.--A 2015 survey on IHC assay validation practices was sent to laboratories subscribed to specific CAP proficiency testing programs and to additional non subscribing laboratories that perform IHC testing. Specific questions were designed to capture laboratory practices not addressed in a 2010 survey. Results.--The analysis was based on responses from 1085 laboratories that perform IHC staining. Ninety-six percent (809 of 844) always documented validation of IHC assays. Sixty percent (648 of 1078) had separate procedures for predictive and nonpredictive markers, 42.7% (220 of 515) had procedures for laboratory-developed tests, 50% (349 of 697) had procedures for testing cytologic specimens, and 46.2% (363 of 785) had procedures for testing decalcified specimens. Minimum case numbers were specified by 85.9% (720 of 838) of laboratories for non-predictive markers and 76% (584 of 768) for predictive markers. Median concordance requirements were 95% for both types. For initial validation, 75.4% (538 of 714) of laboratories adopted the 20-case minimum for non-predictive markers and 45.9% (266 of 579) adopted the 40-case minimum for predictive markers as outlined in the 2014 LPG. The most common method for validation was correlation with morphology and expected results. Laboratories also reported which assay changes necessitated revalidation and their minimum case requirements. Conclusions.--Benchmark data on current IHC validation practices and procedures may help laboratories understand the issues and influence further refinement of LPG recommendations. (Arch Pathol Lab Med. 2017;141:1255-1261; doi: 10.5858/arpa.2016-0559-CP)

In Reply.--The electronic cancer checklists (eCCs) produced by the College of American Pathologists (CAP) enable pathologists to complete the synoptic report within the routine workflow of the anatomic pathology laboratory [...]

To the Editor.--Localized renal masses are increasingly being detected as incidental findings during imaging studies and the clinician must decide to excise, ablate, follow, or perform limited tissue sampling for [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements [...]

The College of American Pathologists (CAP) has been producing the CAP Cancer Protocols (CCPs) since 1986 to aid pathologists in the diagnosis and reporting of cancer cases. (1) Many pathologists [...], Context.--The College of American Pathologists has been producing cancer protocols since 1986 to aid pathologists in the diagnosis and reporting of cancer cases. Many pathologists use the included cancer case summaries as templates for dictation/data entry into the final pathology report. These summaries are now available in a computer-readable format with structured data elements for interoperability, packaged as "electronic cancer checklists." Most major vendors of anatomic pathology reporting software support this model. Objectives.--To outline the development and advantages of structured electronic cancer reporting using the electronic cancer checklist model, and to describe its extension to cancer biomarkers and other aspects of cancer reporting. Data Sources.--Peer-reviewed literature and internal records of the College of American Pathologists. Conclusions.--Accurate and usable cancer biomarker data reporting will increasingly depend on initial capture of this information as structured data. This process will support the standardization of data elements and biomarker terminology, enabling the meaningful use of these datasets by pathologists, clinicians, tumor registries, and patients. (Arch Pathol Lab Med. 2015;139:587-593; doi: 10.5858/arpa.2014-0082-RA)

Immunohistochemical (IHC) testing is an essential component of the pathologic evaluation of many specimens and increasingly provides key information that helps determine how patients are treated. As with any test, [...], Context.--Laboratories must validate all assays before they can be used to test patient specimens, but currently there are no evidence-based guidelines regarding validation of immunohistochemical assays. Objective.--To develop recommendations for initial analytic validation and revalidation of immunohistochemical assays. Design.--The College of American Pathologists Pathology and Laboratory Quality Center convened a panel of pathologists and histotechnologists with expertise in immunohistochemistry to develop validation recommendations. A systematic evidence review was conducted to address key questions. Electronic searches identified 1463 publications, of which 126 met inclusion criteria and were extracted. Individual publications were graded for quality, and the key question findings for strength of evidence. Recommendations were derived from strength of evidence, open comment feedback, and expert panel consensus. Results.--Fourteen guideline statements were established to help pathology laboratories comply with validation and revalidation requirements for immunohistochemical assays. Conclusions.--Laboratories must document successful analytic validation of all immunohistochemical tests before applying to patient specimens. The parameters for cases included in validation sets, including number, expression levels, fixative and processing methods, should take into account intended use and should be sufficient to ensure that the test accurately measures the analyte of interest in specimens tested in that laboratory. Recommendations are also provided for confirming assay performance when there are changes in test methods, reagents, or equipment. (Arch Pathol Lab Med. 2014; 138:1432-1443; doi: 10.5858/arpa.2013-0610-CP)

The human epidermal growth factor receptor 2 gene ERBB2 (HER2) is an important prognostic marker and therapeutic target for breast cancer. HER2 is amplified in 20% of invasive breast cancers, [...], Context.--The American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) published guidelines in 2007 regarding testing accuracy, interpretation, and reporting of results for HER2 studies. A 2008 survey identified areas needing improved compliance. Objective.--To reassess laboratory response to those guidelines following a full accreditation cycle for an updated snapshot of laboratory practices regarding ASCO/CAP guidelines. Design.--In 2011, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program identical to the 2008 survey. Results.--Of the 1150 surveys sent, 977 (85.0%) were returned, comparable to the original survey response in 2008 (757 of 907; 83.5%). New participants submitted 124 of 977 (12.7%) surveys. The median laboratory accession rate was 14 788 cases with 211 HER2 tests performed annually. Testing was validated with fluorescence in situ hybridization in 49.1% (443 of 902) of the laboratories; 26.3% (224 of 853) of the laboratories used another IHC assay. The median number of cases to validate fluorescence in situ hybridization (n = 40) and IHC (n = 27) was similar to those in 2008. Ninety-five percent concordance with fluorescence in situ hybridization was achieved by 76.5% (254 of 332) of laboratories for [IHC.sup.-] findings and 70.4% (233 of 331) for [IHC.sup.+] cases. Ninety-five percent concordance with another IHC assay was achieved by 71.1% (118 of 168) of the laboratories for negative findings and 69.6% (112 of 161) of the laboratories for positive cases. The proportion of laboratories interpreting HER2 IHC using ASCO/CAP guidelines (86.6% [798 of 921] in 2011; 83.8% [605 of 722] in 2008) remains similar. Conclusions.--Although fixation time improvements have been made, assay validation deficiencies still exist. The results of this survey were shared within the CAP, including the Laboratory Accreditation Program and the ASCO/CAP panel revising the HER2 guidelines published in October 2013. The Laboratory Accreditation Program checklist was changed to strengthen HER2 validation practices. (Arch Pathol Lab Med. 2014; 138:876-884; doi: 10.5858/arpa.2013-0731-CP)

Publication of the 2007 American Society of Clinical Oncology/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer represented a significant [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements [...]

The College of American Pathologists (CAP) is committed to helping pathologists and the medical specialty of pathology successfully implement genomically informed, personalized, precision health care. As part of that mission, [...], Context.--Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Clinical preanalytic variables are the focus of this study. Objectives.--To define the essential preanalytic variables (data fields) that should be attached to every collected biospecimen and to provide a complete list of such variables, along with their relative importance, which can vary, depending on downstream use, institutional needs, and information technology capabilities. Design.--The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a Biorepository Working Group to develop a ranked list of the preanalytic variables for annotating biospecimens. Members of the working group were experts in anatomic, clinical, and molecular pathology; biobanking; medical informatics; and accreditation. Several members had experience with federal government programs, such as the National Cancer Institute&apos;s Biospecimens and Biorepository Branch and the National Cancer Institute&apos;s Community Cancer Center Program. Potential preanalytic variables were identified and ranked along with available supporting evidence, definitions, and potential negative effects if the variable was not attached to the biospecimen. Additional national and international stakeholders reviewed the draft manuscript. Results.--The ranked listing of 170 preanalytic variables produced can be used as a guide for site-specific implementation into patient care and/or research biorepository processes. Conclusions.--In our collective experience, it is often difficult to choose which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research. The provided ranked list should aid in the selection of preanalytic variables for a given biospecimen collection. (Arch Pathol Lab Med. 2014; 138:526-537; doi: 10.5858/arpa.2013-0250-CP)

In 2007, a joint Expert Panel convened by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) met to develop guidelines for when and how [...], Purpose. To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. Methods. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. Results. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. Recommendations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. (Arch Pathol Lab Med. 2014; 138:241-256; doi: 10.5858/arpa.2013-0953-SA)

The College of American Pathologists (CAP) has been developing guidelines on cancer data reporting for more than 25 years, with more than 80 regularly updated cancer case summaries now available [...]

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements [...]

In recent years, immunohistochemical (IHC) assays have been rapidly and prolifically incorporated into everyday surgical pathology. While other areas of the laboratory have detailed requirements for diagnostic performance, IHC staining [...], * Context.--The immunohistochemistry (IHC) laboratory represents a dynamic area of surgical pathology with limited practice guidelines. Studies have shown significant interlaboratory variability in results. Objective.--To establish baseline parameters for IHC validation procedures and practice, and to assess their feasibility of implementation. Design.--In September 2010, a questionnaire was distributed by the College of American Pathologists. It was composed of 32 questions relating to nonpredictive assays as well as non-US Food and Drug Administration (non-FDA)-approved, predictive IHC assays other than human epidermal growth factor 2 (HER2/neu). Results.--For non-FDA approved, nonpredictive IHC assays, 68% of laboratories had a written validation procedure. Eighty-six percent of laboratories validated the most recently introduced nonpredictive antibody. Seventy-five percent used 21 or fewer total cases for the validation and 40% used weakly or focally positive cases. Forty-six percent of respondents had a written procedure for validation procedures for non-FDA approved, predictive marker IHC assays other than HER2/neu. Seventy-five percent of laboratories validated the most recently introduced predictive antibody other than HER2/neu. Fewer than half used 25 or more cases for the validation, and 47% used weakly or focally positive cases. Conclusion.--Some laboratories have written validation procedures that appear to build upon HER2/neu testing guidelines. Some laboratories also manage to validate new antibodies according to those standards; however, many do not. There appears to be a need for further validation guideline development for nonpredictive and non-FDA approved predictive antibody IHC assays. (Arch Pathol Lab Med. 2013; 137:19-25; doi: 10.5858/arpa.2011-0676-CP)

To comply with regulatory and accreditation requirements, most institutions have adopted policies for communicating critical test results from clinical pathology laboratories, radiology departments, and other testing areas, such as the [...], * Context.--Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses. Objective.--To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology. Design.--A comprehensive literature search was conducted and reviewed by an expert panel. Results.--A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements. Conclusions.--Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient&apos;s course. Further details of this statement are provided. (Arch Pathol Lab Med. 2012; 136:148-154; doi: 10.5858/arpa.2011-0400-SA)

Translational research done in conjunction with clinical trials is an important tool in developing new treatment modalities and improving patient outcomes. Most current randomized phase III clinical trials of cancer [...], Context.--The number of paraffin blocks submitted for patients enrolled in clinical research trials appears to be declining. Objective.--To obtain information on laboratory policies and procedures in complying with requests to submit paraffin blocks for research. Design.--A questionnaire was sent to members of a voluntary market research panel composed of pathologists representing a broad spectrum of experience and practice settings. The questions addressed departmental policies and the likely responses to requests to submit pathology materials for patients enrolled in clinical trials. Results.--The survey was completed by 609 of 762 pathologists (80%) who responded to the invitation. More than 90% of respondents stated that they comply with these requests. Although 14% have a policy precluding the release of blocks for research, 84% of those will send limited tissue samples in lieu of blocks. When tumor is confined to a single block, most laboratories will not release the block but will send unstained slides. Very few laboratories require reimbursement before releasing tissues. Conclusions.--Pathologists attempt to comply with requests for materials but usually refuse to release the only diagnostic paraffin block so that materials are retained for possible future needs. Other problems identified in this survey include difficulties in getting blocks returned when needed and poor communication between researchers and laboratories. Lack of reimbursement and inadequate consent are not significant barriers to release of materials. (Arch Pathol Lab Med. 2011;135:870-873)

ESTROGEN RECEPTOR PHYSIOLOGY AND MEASUREMENT The estrogen receptor (ER) is the paradigm tumor marker for management of patients with cancer. For more than three decades, ER has been the most [...], * Purpose.--To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. Methods.--The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Results.--Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria. Recommendations.--The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

Validation of a clinical laboratory test means confirmation, through a defined process, that the test performs as intended or claimed. Proper validation provides reasonable, but not absolute, assurance that a [...], * Context.--Estrogen receptor and progesterone receptor status is assessed on all newly diagnosed, invasive breast carcinomas and in recurrences to determine patient eligibility for hormonal therapy, but 10% to 20% of estrogen receptor and progesterone receptor test results are discordant when tested in multiple laboratories. Objective.--To define the analytic (technical) validation requirements for estrogen receptor and progesterone receptor immunohistochemistry assays used to select patients for hormonal therapy. Data Sources.--Literature review and expert consensus. Conclusions.--A standardized process for initial test validation is described. We believe adoption of this process will improve the accuracy of hormone-receptor testing, reduce interlaboratory variation, and minimize false-positive and false-negative results. Required ongoing assay assessment procedures are also described. (Arch Pathol Lab Med. 2010;134:930-935)

Human epidermal growth receptor 2 gene ERBB2 (commonly referred to as HER2) amplification status is an important prognostic marker in breast cancer and is a factor in determining patient therapy. [...], Context.--To ensure quality human epidermal growth receptor 2 (HER2) testing in breast cancer, the American Society of Clinical Oncology/College of American Pathologists guidelines were introduced with expected compliance by 2008. Objective.--To assess the effect these guidelines have had on pathology laboratories and their ability to address key components. Design.--In late 2008, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding pathology practice characteristics and assay validation using fluorescence in situ hybridization or another IHC laboratory assay and assessed pathologist HER2 scoring competency. Results.--Of the 907 surveys sent, 757 (83.5%) were returned. The median laboratory accessioned 15 000 cases and performed 190 HER2 tests annually. Quantitative computer image analysis was used by 33% of laboratories. In-house fluorescence in situ hybridization was performed in 23% of laboratories, and 60% of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40%, on the resection specimen in 6%, and on either in 56% of laboratories. Testing was validated with only fluorescence in situ hybridization in 47% of laboratories, whereas 10% of laboratories used another IHC assay only; 13% used both assays, and 12% and 15% of laboratories had not validated their assays or chose "not applicable" on the survey question, respectively. The 90% concordance rate with fluorescence in situ hybridization results was achieved by 88% of laboratories for IHC-negative findings and by 81% of laboratories for IHC-positive cases. The 90% concordance rate for laboratories using another IHC assay was achieved by 80% for negative findings and 75% for positive cases. About 91% of laboratories had a pathologist competency assessment program. Conclusions.--This survey demonstrates the extent and characteristics of HER2 testing. Although some American Society of Clinical Oncology/College of American Pathologists guidelines have been implemented, gaps remain in validation of HER2 IHC testing. (Arch Pathol Lab Med. 2010;134:728-734)

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting [...]