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Anatomic Pathology Selected Abstracts, 3/13

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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.

Immunohistochemical assay versus Oncotype DX qRT-PCR assay for estrogen and progesterone receptors

Estrogen receptor status is a strong predictor of response to hormonal therapy in breast cancer patients. Its presence and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is known to occur in estrogen receptor-negative, progesterone receptor-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. As a component of its Oncotype DX assay, Genomic Health recently began reporting quantitative estrogen and progesterone receptor results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at Magee-Womens Hospital in Pittsburgh, the authors reviewed 464 breast cancer cases evaluated for estrogen and progesterone receptor by both immunohistochemistry and the Oncotype DX assay. They found good correlation for estrogen receptor status between both assays (98.9 percent concordance), with immunohistochemistry being slightly more sensitive. Concordance for progesterone receptor was 94.2 percent between immunohistochemistry and qRT-PCR, with immunohistochemistry again more sensitive. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for estrogen receptor (correlation coefficient, 0.579) and progesterone receptor (correlation coefficient, 0.685). Due to hormone receptor immunohistochemistry having higher sensitivity and additional advantages—that is, preservation of morphology, less expensive, faster, and more convenient—the authors concluded that immunohistochemistry is preferable to qRT-PCR for determining estrogen and progesterone receptor expression.

Kraus JA, Dabbs DJ, Beriwal S, et al. Semi-quantitative immunohistochemical assay versus Oncotype DX qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study. Mod Pathol. 2012;25:869–876.

Correspondence: Dr. R. Bhargava at rbhargava@mail.magee.edu

Accuracy and precision of endometrial intraepithelial neoplasia diagnosis

Endometrial intraepithelial neoplasia applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. The authors conducted an international study in which they estimated the accuracy and precision of endometrial intraepithelial neoplasia (EIN) diagnosis among 20 reviewing pathologists who were in different practice environments and had differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess the diagnostic accuracy of the 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook or online EIN diagnostic guidelines, or both. The demographics of the reviewing pathologists and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus. The interobserver weighted kappa values of three-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of the reviewing pathologists averaged 0.72. The reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, in their nonrandom response to potentially confounding diagnostic features, such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparation. The authors concluded that EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but they are influenced by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

Usubutun A, Mutter GL, Saglam A, et al. Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists. Mod Pathol. 2012;25:877–884.

Correspondence: Dr. A. Usubutun at ausubutu@hacettepe.edu.tr

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