Potential for False-Positive Staining With a Rabbit Monoclonal Antibody to Progesterone Receptor (SP2): Findings of the UK National External Quality Assessment Scheme for Immunocytochemistry and FISH Highlight the Need for Correct Validation of Antibodies on Introduction to the Laboratory
This study focused on recent assessment results from the United Kingdom National External Quality Assessment Scheme for Immunocytochemistry and Fluorescence In-Situ Hybridisation breast hormone receptor module in which participants were asked to demonstrate progesterone receptors (PRs). The slides consisted of 3 infiltrating ductal breast carcinomas, previously classified as a high PR expresser, a moderate to low PR expresser, and a negative tumor. During this assessment, 2 commercial rabbit monoclonal antibodies, SP2 (Lab Vision/NeoMarkers, Fremont, CA), and 1E2 (Ventana, Tucson, AZ) were used by 15% of the participants. The SP2 rabbit monoclonal antibody showed false-positive and nonspecific staining on the previously established PR-tumor. This article highlights the necessity for all clinical laboratories to validate immunohistochemical methods and protocols when using newly marketed antibodies such as SP2; use composite tissue blocks with known levels of tumor expression such as a high, mid, and negative expression; and participate in internal and external quality assessment schemes, which can highlight potential technical issues in laboratory methods.
Available from: PubMed Central
- "This separation persists for the node-negative subgroup (Intermediate Risk 2) as well as the node-positive subgroup (Intermediate Risk 3), although in this latter subgroup the ER-/PR+/HER2- subtype is rather small. The existence of the ER-/PR+ subtypes is controversial [29,30] although some believe it is a distinctive subtype with a poor prognosis . Our results, while not definitive in any sense, would tend to agree with this latter interpretation. "
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ABSTRACT: The 2007 St Gallen international expert consensus statement describes three risk categories and provides recommendations for treatment of early breast cancer. The set of recommendations on how to best treat primary breast cancer is recognized and used by clinicians worldwide. We now examine the variability of five-year survival of the 2007 St Gallen Risk Classifications utilizing the ER/PR/HER2 subtypes.
Using the population-based California Cancer Registry, 114,786 incident cases of Stages 1-3 invasive breast cancer diagnosed between 2000 and 2006 were identified. Cases were assigned to Low, Intermediate, or High Risk categories. Five-year-relative survival was computed for the three St Gallen risk categories and for the ER/PR/HER2 subtypes for further differentiation.
There were 9,124 (13%) cases classified as Low Risk, 44,234 (65%) cases as Intermediate Risk, and 14,340 (21%) as High Risk. Within the Intermediate Risk group, 33,735 (76%) were node-negative (Intermediate Risk 2) and 10,499 (24%) were node-positive (Intermediate Risk 3). For the High Risk group, 6,149 (43%) had 1 to 3 positive axillary lymph nodes (High Risk 4) and 8,191 (57%) had four or more positive lymph nodes (High Risk 5). Using five-year relative survival as the principal criterion, we found the following: a) There was very little difference between the Low Risk and Intermediate Risk categories; b) Use of the ER/PR/HER2 subtypes within the Intermediate and High Risk categories separated each into a group with better five-year survival (ER-positive) and a group with worse survival (ER-negative), irrespective of HER2-status; c) The heterogeneity of the High Risk category was most evident when one examined the ER/PR/HER2 subtypes with four or more positive axillary lymph nodes; (d) HER2-positivity did not always translate to worse survival, as noted when one compared the triple positive subtype (ER+/PR+/HER2+) to the triple negative subtype (ER-/PR-/HER2-); and (e) ER-negativity appeared to be a stronger predictor of poor survival than HER2-positivity.
The use of ER/PR/HER2 subtype highlights the marked heterogeneity of the Intermediate and High Risk categories of the 2007 St Gallen statements. The use of ER/PR/HER2 subtypes and correlation with molecular classification of breast cancer is recommended.
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ABSTRACT: In land mobile systems, a distance of separation is needed to
provide sufficient isolation between two systems so that they can
operate without interference. In order to increase spectrum utilization,
it is worth while to explore if such two systems can be brought closer
together at an acceptable probability of interference. This paper
introduces a methodology to calculate such a probability of
interference, in a land mobile duplex system context
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ABSTRACT: Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan-Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR- patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.
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