Summary Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a ...semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called “Score the Core” (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers.
Objectives Our objective was to identify risk factors associated with survival in patients who underwent pulmonary metastasectomy for soft tissue or bone sarcoma and to create a risk stratification ...model. Methods A retrospective review of the prospectively maintained University of California Los Angeles Sarcoma Database was performed. Clinical, pathologic, and treatment variables were analyzed for overall survival and disease-free survival. Univariate and multivariate analyses were performed, and variables that were identified as significant were included to create a risk model. A total of 155 patients who underwent pulmonary metastasectomy for soft tissue sarcoma (n = 108 patients) or bone sarcoma (n = 47 patients) from 1994 to 2010 were identified. Results Multivariate analysis identified 7 factors associated with poor overall survival: age more than 45 years, disease-free interval less than 1 year, thoracotomy, synchronous disease, location and type of sarcoma (soft tissue vs bone sarcoma), and performance of a lobectomy. The number of factors present was associated with poor overall survival, which varied widely from 64% in patients with 2 factors to 3% in those with 5 factors. Conclusions We have identified prognostic variables associated with overall survival after lung metastasectomy. Our model may be used as a risk stratification model to guide treatment decisions on the basis of the number of risk factors present. Although prospective studies are warranted to determine the benefit of surgical intervention in all cohorts compared with other local therapies or medical therapy, given the attendant dismal prognosis in patients with 5 or more risk factors, the benefit of surgical resection in this group is questioned.
Summary The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF ...are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% 5/6 versus 17% 1/12, P = .0015) and HB-EGF expression (100% 6/6 versus 50% 6/12, P = .0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r = 0.9131 ( P = .027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P = .025 for HB-EGF; and 61.5%/42.9%/20.0%, P = .021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P = .326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required.
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