The expression of estrogen receptor-α and related genes has emerged as one of the major determinants of molecular classification of invasive breast cancers. Expression of a second estrogen receptor, estrogen receptor-β (ER-β), has not been previously evaluated in a large population-based study. Therefore, the authors examined ER-β expression in a large population of women with breast cancer to assess its relationship to molecular categories of invasive breast cancer. They constructed tissue microarrays from the paraffin blocks of 3,093 breast cancers that developed in women enrolled in the Nurses’ Health Study. Tissue microarray sections were immunostained for ER-β, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor (EGFR), and a monoclonal antibody to ER-β. Cancers were categorized as luminal A (ER-α+ and/or PR+ and HER2–), luminal B (ER-α+ and/or PR+ and HER+), HER2 (ER-α–, PR–, and HER2+), and basal like (ER-α–, PR–, HER2–, and EGFR or cytokeratin 5/6+). The authors analyzed the relationship between expression of ER-β and molecular class of invasive breast cancer. They found that, overall, 68 percent of breast carcinomas were ER-β+. Expression of ER-β was significantly associated with expression of ER-α (P<0.0001) and PR (P<0.0001) and was inversely related to expression of HER2 (P=0.004), cytokeratin 5/6 (P=0.02), and EGFR (P=0.006). Among 2,170 invasive cancers with complete immunophenotypic data, 73 percent were luminal A, five percent luminal B, six percent HER2, and 11 percent basal like. ER-β expression was significantly related to molecular category (P<0.0001) and was more common in luminal A (72 percent of cases) and B (68 percent of cases) than in HER2 or basal-like types. However, despite their being defined by the absence of ER-β expression, 55 percent of HER2-type and 60 percent of basal-like cancers showed expression of ER-α. The authors concluded that the role of ER-β in the development and progression of breast cancers defined by lack of expression of ER-α merits further investigation.
Marotti JD, Collins LC, Hu R, et al. Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study. Mod Pathol. 2010;23:197–204.
Correspondence: Dr. L. C. Collins at firstname.lastname@example.org
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Human papillomavirus is a causative agent in a subset of head and neck squamous cell carcinomas. These human papillomavirus (HPV)-related cancers have a clinicopathologic profile that diverges from HPV-negative head and neck squamous cell carcinomas (HNSCCs). Accordingly, HPV testing may soon be integrated into the standard pathologic assessment of HNSCCs. The authors conducted a study to compare HPV in situ hybridization (ISH) and p16 immunohistochemistry (IHC). They prospectively collected data for all patients with head and neck carcinomas who had undergone HPV testing at the Johns Hopkins Hospital, Baltimore, as part of clinical care during a 57-month period. HPV testing consisted of concurrent HPV16 ISH and p16 IHC. Wide-spectrum HPV ISH was reserved for p16-positive cases that were HPV-16 negative. HPV analysis was performed on 256 head and neck carcinomas to predict clinical outcomes (56 percent), localize primary tumor origin (21 percent), establish tumor classification (nine percent), determine patient eligibility for vaccine trials (eight percent), or satisfy patient curiosity (five percent). The authors determined that 182 (71 percent) tumors were HPV positive. HPV positivity correlated with oropharyngeal site (82 versus nine percent) and male gender (77 versus 48 percent). P16 positivity was present in all 176 HPV16-positive cases and in 19 of 80 (24 percent) cases that were HPV-16 negative. In six (32 percent) discordant cases, p16 expression occurred because of the presence of another HPV type. The authors concluded that a feasible strategy that incorporates p16 IHC and HPV ISH can detect HPV in a high percentage of oropharyngeal carcinomas. Oncologists frequently request HPV status to estimate clinical outcome. Pathologists use it to establish tumor classification and determine site of tumor origin.
Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer. 2010;116:2166–2173.
Correspondence: Dr. William H. Westra at email@example.com
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The authors conducted a study to evaluate the prognostic value of Ki67 in relation to established prognostic factors in lymph node-negative breast cancer. They also evaluated whether prognostic impact was dependent on estrogen receptor status and histological grade. They analyzed Ki67 on tissue microarrays from 200 premenopausal patients with five years of followup. In univariate analysis, Ki67 (20 percent or less versus more than 20 percent) was a prognostic factor for distant disease-free survival (hazard ratio, 2.7; 95 percent confidence interval, 1.3–5.4; P=0.005) and overall survival (hazard ratio, 4.9; 95 percent confidence interval, 1.7–14; P=0.003). When stratifying for estrogen receptor status and histological grade, Ki67 was a significant prognostic factor for distant disease-free survival and overall survival only in the ER-positive group and only in patients with histological grade 2, respectively. In multivariate analysis, human epidermal growth factor receptor 2 and age were independent prognostic factors for distant disease-free survival, whereas Ki67, histological grade, and tumor size were not. However, Ki67 was an independent prognostic factor in the 87 percent of patients who had not received adjuvant medical treatment. Agreement between the three readers was very good (k values, 0.83–0.88). Furthermore, Ki67 was a significant prognostic factor for all three investigators (hazard ratio, 2.7–3.2). The authors concluded that their study showed that Ki67 is a prognostic factor in node-negative breast cancer. It is noteworthy that the prognostic information about Ki67 is restricted to ER-positive patients and patients with histological grade 2. Ki67, as an easily assessed and reproducible proliferation factor, may be an alternative or complement to histological grade as a prognostic tool and for selecting adjuvant treatment.
Klintman M, Bendahl PO, Grabau D, et al. The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer. Mod Pathol. 2010;23:251–259.
Correspondence: Dr. M. Klintman at firstname.lastname@example.org
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Half of all patients with head and neck squamous cell carcinoma can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. The authors developed a novel risk model that can become a basis for developing new treatment paradigms. They reported on the performance of their model in a new multicenter cohort. The authors identified eligible patients from three institutions—Montefiore Medical Center, University of Manitoba, and New York University Medical Center—and one of the study authors reviewed pathology slides from these patients’ resection specimens. Risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusting for potential confounders. A teaching module was also developed. Attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients. The validation cohort consisted of 305 patients from the aforementioned institutions, representing 311 primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, and larynx. The median followup period for all patients was 27 months. The authors found that risk category predicted time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0) by Kaplan-Meier analysis. High-risk status was significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015; hazard ratio, 2.32; 95 percent confidence interval, 1.18–4.58), compared with collapsed intermediate and low-risk groups. The authors also demonstrated substantial interrater agreement (k value, 0.64) and very good rater agreement when compared with the standard (k value, 0.87). The authors concluded that they demonstrated significant predictive performance of the risk model in a new cohort of patients with primary head and neck squamous cell carcinoma adjusted for confounders. Their training experience supports the feasibility of adapting the risk model in clinical practice.
Brandwein-Gensler M, Smith RV, Wang B, et al. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2010;34:676–688.
Correspondence: Dr. Margaret Brandwein-Gensler at email@example.com
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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; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.