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Lecture 13 - Lecture#14 Thursday-1 Pathologists get...

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Lecture #14 – Thursday, 5/15/08 - 1 - Pathologists – get biopsies, tissue samples and characterizes them through microscopy for changes that are typically in stages of breast cancer - In breast cancer - Benign vs. hyperplastic vs. - Degree of anaplasia (or de-differentiation – well or poorly differentiated?) - Uniform nuclear morphology? Nuclei of cancer cells often start to look atypical, not the normal size of a nucleus particularly for an epithelial cell - Degree of proliferation (abnormal?) - Evidence of the cancer arising in duct or lobe? Wheel of Prognosis: what to look at in Breast Cancer - Tumor Type - Lymph node metastasis? - Size of tumor - Different histological characteristics like nuclear size - Ploidy of DNA? Diploid, tetraploid, or endploid - Presence or absence of androgen receptors? - Proliferation index o Stain for Ag specific for S phase (Ki 67, pCNA), cells that are positive are the ones going through S phase division (proliferating) o Number of cells in a given section of slide that are positive for the antigen is roughly correlated with the number of cells that are proliferating. And if that is at high level, then that is a highly proliferative piece of tissue. - Amplification of known oncogenes (ex. Her-2/neu) - Evidence of mutations (DNA level) - Evidence of expression of something like EGFR - Tools of the trade that a pathologist can use on a sample to determine what stage a cancer is at - What levels of treatment may or may not help Factors influencing outcome of patient: - Size of tumor: larger tumor, decreased number of patients who survive (lower survival rate) o <2 cm, ~11% of lymph node negative (no evidence of metastasis in adjacent lymph nodes) patients will show recurrence in 5 years. 89% will be tumor free later. o >5 cm, 25-30% of patients will relapse regardless of what their lymph node status is o More metastases, increased likelihood of recurrence o Gross size of tumor can have an impact on predicted survival rate - Histologic grade: the greater the grade, the less chance for survival. Histology is just looking at slides. o Assayed by evidence of nuclear changes, microscopy basically. Note about statistics like these : Some people could have a baseball sized tumor, have it surgically removed and be perfectly fine five years later. Other people can come with a
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Lecture #14 – Thursday, 5/15/08 - 2 - microscopic tumor and die within a year. There is a spread of results and there are no absolutes in this type of thing. Statistics are not absolute . They are an expression of a general trend observed amongst people with shared characteristics. “Statistical slot” - Estrogen Receptor Status: the loss of estrogen receptors is related to a negative outcome. o Estrogen receptor negative tumors don’t respond to drug therapies meant to reduce tumor size by inhibiting those receptors (ex. Tamoxifen).
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