Biomedical subjects

Edward Clifford

Publications and source records attributed to Edward Clifford.

5 recordsLinked to original sources

PubMed2006

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues.

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.

Breast Neoplasms↗

PubMed2004

HER-2 gene amplification can be acquired as breast cancer progresses.

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.

Antibodies, Monoclonal↗

PubMed2003

Interpretive disparity among pathologists in breast sentinel lymph node evaluation.

BACKGROUND: Immunohistochemical staining on breast sentinel lymph nodes (SLN) is controversial. METHODS: Twenty-five SLN cases were reviewed by 10 pathologists (three academic, seven private) including 5 negative by both hematoxylin and eosin (H&E) and immunohistochemistry, 11 micrometastases (<2 mm) negative by H&E but positive by immunohistochemistry, and 8 micrometastases and 1 macrometastasis (>2 mm) positive for both H&E and immunohistochemistry. Answers included "positive," "negative," and "indeterminate" for each slide. RESULTS: The mean number of incorrect responses was 6.6 for immunohistochemistry and 5 for H&E. Twelve percent of cases were correct by all 10 pathologists; 80% of positive IHC cases had at least one pathologist score it incorrectly. As tumor cells decrease in number, incorrect responses increase. When tumor cells numbered less than 10, more than 30% of pathologists answered incorrectly. CONCLUSIONS: As tumor cells decrease in number pathologists' ability to recognize them decreases. We propose adding "indeterminate" to "positive" and "negative" when tumor cells number less than 10.

Breast Neoplasms↗

PubMed2002

Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant.

PURPOSE: Numerous studies of circulating epithelial cells (CECs)have been described in cancer patients, and genetic abnormalities have been well documented. However, with one exception in colorectal cancer, there has been no report of matching the genetic abnormalities in the CECs with the primary tumor. The purpose of this investigation was to determine (a) whether CECs in patients including those with early tumors are aneusomic and (b) whether their aneusomic patterns match those from the primary tumor, indicating common clonality. EXPERIMENTAL DESIGN: Thirty-one cancer patients had CECs identified by immunofluorescence staining using a monoclonal anti-cytokeratin antibody. Their CECs were analyzed by enumerator DNA probes for chromosomes 1, 3, 4, 7, 8, 11, or 17 by dual or tricolor fluorescence in situ hybridization. Touch preparations of the primary tumor tissue were available from 17 of 31 patients and hybridized with the same set of probes used to genotype the CECs. RESULTS: The number of CECs from each patient ranged from 1-92 cells/cytospin. CECs showed abnormal copy numbers for at least one of the probes in 25 of 31 patients. Touch preparations from the primary tumors of 13 patients with aneusomic CECs were available. The pattern of aneusomy matched a clone in the primary tumor in 10 patients. CONCLUSIONS: We conclude that the vast majority of CECs in breast, kidney, prostate, and colon cancer patients are aneusomic and derived from the primary tumor.

Chromosome Aberrations↗

PubMedDate not supplied

Intraoperative cytologic diagnosis of breast sentinel lymph nodes in the routine, nonacademic setting: a highly specific test with limited sensitivity.

Intraoperative determination of metastatic breast carcinoma in sentinel lymph nodes (SLNs) by cytologic methods has been proposed as highly specific and sensitive. Much of these data are derived from academic institutes with highly trained personnel and without axillary dissection occurring as a direct result of the intraoperative interpretation. This prospective study was undertaken to assess the sensitivity and specificity of cytology in the routine, private-practice, intraoperative setting. A total of 207 SLNs from 96 breast carcinoma patients were evaluated by intraoperative cytologic preparations by general surgical pathologists; positive results led to axillary lymphadenectomy. Ten nodes were positive by intraoperative cytology (IC). Permanent section analysis confirmed the presence of carcinoma in the IC-positive cases and documented carcinoma in 19 of the IC-negative cases. IC sensitivity and specificity were 34% and 100%, respectively. False-negative IC interpretations occurred in nodes with occult micrometastases (12 of 19 nodes) and lobular carcinoma (6 of 19 nodes). Only one of eight grossly positive sentinel nodes resulted in a false-negative IC. While near-perfect specificity and high sensitivity can be achieved with grossly positive sentinel nodes by IC, sensitivity is quite low in cases with micrometastatic and lobular carcinoma.

Breast Neoplasms↗