Biological Stain Commission. San Antonio 2009.

Breast pathology is the foundation of quality breast health care. The information provided in a pathology report is the guiding light in directing immediate therapy and the follow up clinical management. There is no doubt that accuracy of diagnostic and prognostic/predictive information has a long lasting impact on the quality of life and the final outcome of breast cancer patients. To achieve the optimal care, it is essential to engage knowledgeable pathologists who are interested in breast pathology in an integrated breast center concept with the ability to directly communicate with the physicians involved in breast health care. This lecture is designed to provide an overview of the role of pathologists in providing diagnostic and prognostic/predictive information. Emphasis will be placed on the impact of the level of the accuracy of the pathology reports in, under or over treatment of patients with breast lesions. This will be achieved by the review of the reports in the literature in regard to the frequency of change of the management of breast cancer patients upon second review of pathology cases. Examples will be presented to describe the commons pitfalls in diagnostic breast pathology and how to minimize the frequency of these diagnostic errors. Attempts will be made to show the effect of direct communication with the radiologists, surgeons, and oncologists in order to achieve optimal knowledge about the nature of the abnormalities that are seen clinically or are detected by breast imaging. In addition, the significance of adherence to the established guidelines about the traditional and newly recognized prognostic and predictive in breast cancer will be discussed in detail. At the end of the session suggestions will be made about taking measures to minimize errors in the practice of breast pathology.

Immunohistochemistry continues to obtain the respect it deserves because it offers volumes of information that range from the determination of protein distributions throughout the various tissues of the body to validation of target expression in normal and diseased rodent and human tissues. In this discussion, I will present the applications of IHC to a few of our Drug Discovery programs that are focused on the cancer microtumor environment and Alzheimer’s disease (AD). Both begin with the goal of characterizing the distribution of potential targets in normal tissues using IHC. In each instance, what appeared to be a straightforward project expanded into discoveries leading to new understanding about the expression patterns of these targets as well as novel insights into these two fields of research. The first project began with a simple and straightforward understanding of the distribution of a protease-activated receptor-2 (PAR2), the reputed trypsin receptor, in normal human tissues. This prompted additional work that expanded into understanding the expression patterns of PAR2 in human cancers. In addition, these faults fueled hypotheses, which were later validated through in vitro experimentation. Although much of this work focused on the expression patterns of PAR2 (and PAR1, the thrombin receptor) in tumor cells, it was the finding of PAR2 in the tumor microenvironment that created additional excitement. In addition, we discovered similar data for another target, serine palmitoyltransferase (SPT), which I will discuss further in this talk with the focus on the role of the tumor microenvironment in tumor growth. The other project addressed the expression of the alpha 7 nicotinic receptor (α7) in AD brains. What began as a tightly focused objective led to some important discoveries that helped to explain the observed AD in histopathology. These findings include neurons overburdened with intracellular amyloid that eventually degenerate in AD brains, a dysfunctional blood-brain barrier, mechanism explaining dense-core amyloid plaque formation, and the possible role of autoimmunity in AD. I should note that, along the way, our data has been continuously challenged by certain resistant factions within the AD research community but was later confirmed by others. I will present how the applications of IHC on AD tissues led to over a dozen publications and have helped to create novel hypotheses about the neuropathology of AD.

The fixation and processing of breast tissues has presented some unique challenges in order to adhere to the new Her2neu guidelines presented by ASCO and CAP. There have been questions and concerns to arise about the length of fixation time in formalin through routine processing. A study was done to provide some data on breast tissue that was fixed in formalin from 6 hours minimum up to 72 hours. Processing the breast tissues both on the traditional tissue processor and utilizing a microwave tissue processor was implemented. IHC ER, PR, Ki67, p53 and Her2neu was performed on these breast samples revealing the effects on both the length of fixation and processing.