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Quantitative FISH analysis on interphase nuclei may improve diagnosis of DNA diploid breast cancersDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2002
Abstract The detection of DNA aneuploid cells using flow cytometry is an indication for the presence of tumor cells, but when DNA diploid cells are found in 25,33% of the cases, the diagnostic and prognostic significance of DNA ploidy is more limited. We analyzed interphase nuclei after in situ hybridization and using image cytometry on 50 breast tumors with diploid DNA content to investigate whether early chromosome rearrangements were detectable and if their occurrence was clinically significant. Imbalances between the two arms of chromosome 1 were found in 55% of the cases and values ranged from 1.5,3.0. Comparison with histological data showed that Grade I tumors mainly have imbalances (67%) and that Grade III tumors were mainly without the imbalance (67%), whereas Grade II tumors were intermediate (50% imbalance). These data suggest that the diagnosis of DNA diploid cases may be improved by using interphase FISH. In addition, the data also indicates that early breast tumors may have different genetic origins, which is important in the comprehension of tumor malignancy in early stages, especially for preinvasive lesions. Diagn. Cytopathol. 2002;26:213,216. © 2002 Wiley-Liss, Inc. [source]
Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade gliomaCANCER, Issue 6 2004
Peter Hau M.D.
Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source]
Cyclooxygenase-2 in oligodendroglial neoplasmsCANCER, Issue 7 2003
Elias A. Castilla M.D.
Abstract BACKGROUND Although increased expression of cyclooxygenase-2 (COX-2) has been described in association with a variety of neoplasms, including tumors of astrocytic derivation, limited data are available on COX-2 expression in oligodendrogliomas. METHODS The current study retrospectively reviewed 53 oligodendrogliomas and 7 oligodendroglioma-predominant oligoastrocytomas (mixed gliomas) for COX-2 expression and MIB-1 proliferative index (by immunohistochemistry) and for chromosome 1p status (by fluorescence in situ hybridization). RESULTS Patients included 35 males and 25 females, with a mean age of 41 years (range, 12,73 years) at the time of surgery. Forty-four tumor specimens were classified as World Health Organization (WHO) Grade II neoplasms and 16 as WHO Grade III tumors. MIB-1 labeling indices (marker of cell proliferation) ranged from 0 to 22.3 (mean 4.5). Twenty-eight tumor specimens demonstrated allelic loss on chromosome 1p. Positive staining was observed in 17 tumor specimens with COX-2 antibody. COX-2,positive tumor specimens were also evaluated with CD68 (macrophage/microglial cell marker) by coimmunolabeling to confirm that the observed COX-2 immunostaining was not due to immunoreactive macrophages or microglial cells. COX-2 expression, lack of allelic loss at chromosome 1p, and high proliferation indices were associated with decreased survival (P = 0.002, P = 0.009, and P = 0.015, respectively). No correlation with outcome was found with patient gender, age at diagnosis, or histologic grade. CONCLUSIONS Chromosome 1p, COX-2 immunoreactivity, and MIB-1 labeling indices correlated with outcome and were associated with decreased survival. There was not a one-to-one correspondence between COX-2 immunoreactivity and lack of allelic loss at chromosome 1p. Tumors with expression of COX-2 by immunohistochemistry may, in theory, benefit from treatment with therapeutic agents that inhibit COX-2. Cancer 2003;98:1465,72. © 2003 American Cancer Society. DOI 10.1002/cncr.11632 [source]
Histologic grade, stage, and survival in breast carcinoma,,CANCER, Issue 5 2003
Caucasian women, Comparison of African American
Abstract BACKGROUND African American women have lower breast carcinoma survival rates than do Caucasian women. African American women often present with advanced-stage disease and more aggressive tumors as shown by histologic and laboratory-based prognostic factors. Aggressive tumor behavior may be responsible, at least in part, for the advanced stage and reduced survival rates. METHODS The authors investigated the correlation between survival and histologic grade, stage of disease, and tumor size for both African American and Caucasian women who were younger than age 50 years and age 50 years and older. The authors also investigated the distribution of grade within each stage group and the distribution of grade by tumor size. African American and Caucasian women were matched by stage, tumor size, and histologic grade. Survival was represented by 6-year breast carcinoma,specific survival rates. RESULTS Compared with Caucasian women, African American women, regardless of age, had proportionally more Grade III tumors and fewer Grade I and II tumors for all stages combined and for each individual stage group. Similarly, matched for tumor size, African American women had more Grade III tumors and fewer Grade I and II tumors compared with Caucasian women, except for tumors smaller than 1.0 cm. For nearly all combinations of stage and grade regardless of age, the 6-year breast carcinoma,specific survival rate was lower for African American women than for Caucasian women, although it did not always reach statistical significance. CONCLUSIONS Compared with Caucasian women, African American women, regardless of age, presented with proportionally more aggressive tumors for each stage of disease and for each tumor size above 1.0 cm as revealed by the histologic grade. Higher histologic grade may be a significant contributing factor to survival disadvantage for African American women. Cancer 2003;98:908,17. Published 2003 by the American Cancer Society. DOI 10.1002/cncr.11558 [source]
A Decision Tool for Predicting Sentinel Node Accuracy from Breast Tumor Size and GradeTHE BREAST JOURNAL, Issue 6 2007
FRCS (Gen. Surg.), Nathan Coombs BSc
Abstract:, The ability to predict axillary lymph node involvement in breast cancer patients in the preoperative setting is invaluable. This study provides a simple set of formulae to enable clinicians to make informed decisions in the management of screen-detected breast cancer. The tumor pathology reports were obtained of all 4,585 women identified between 1996 and 1999 in New South Wales (NSW) with T1 or T2 breast cancer by the statewide co-ordinated breast screening service (BreastScreen NSW). Equations predicting node positivity were calculated by linear regression analysis and, from published sentinel node false-negative rates, the probability of retrieval of a false-negative axillary lymph node by sentinel node biopsy was calculated for tumors of different size and grade. Node involvement was identified in 1,089 (23.8%) of women. A linear relationship for tumor size, grade, and nodal involvement was predicted by: frequency (%) = 1.5 × tumor size (mm) + 2 (or 6 or 10) for grade I (or II or III) tumors. Assuming a 7.5% false-negative rate, the probability of retrieving a false-negative sentinel node ranged from 0.8% for a patient with a 5 mm, grade I carcinoma to 6.0% for a 50 mm, grade III tumor. These simple formulae are easy to use in a clinical setting. The reference table enables breast surgeons to inform a patient about the absolute probability of false-negative sentinel biopsy rates for patients with screen-detected carcinomas when size can be estimated from preoperative imaging and when tumor grade is often available from preoperative core biopsy. Patients with large, T2 breast tumors may be best treated with axillary dissection rather than sentinel node biopsy alone due to the risk of under-staging the woman's disease and also the high probability of finding a positive sentinel node. [source]
Intraoperative evaluation of sentinel lymph nodes in breast carcinoma by imprint cytology, frozen section and rapid immunohistochemistryDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009
Sharma Upender M.D.
Abstract Sentinel lymph nodes (SLN) isolated in 40 patients of breast carcinoma (stage T1/T2) were evaluated intraoperatively by imprint cytology and frozen section. Rapid immunohistochemistry (IHC) was done in cases where both imprint smears and frozen sections were negative for any metastatic tumor deposits. The results of these different techniques were compared with postoperative paraffin sections taken as "Gold Standard." Nottingham modification of Bloom Richardson scoring system was used for grading the tumors. Further, the correlation of the SLN status with tumor size, grade, and lymphovascular invasion was studied. The sensitivity, specificity, and overall accuracy of imprint cytology were 91.7, 100, and 95% respectively, and those of the frozen section were 95.8, 100, and 97.5% respectively. Examination of multiple serial sections improved the sensitivity and overall accuracy of frozen section. Results of intraoperative rapid IHC were equivalent to final paraffin sections. Histological grade and lymphovascular invasion were in direct correlation with SLN metastasis (P < 0.05). The risk of lymphovascular invasion increased from 22.2% in grade I tumors to 85.7% in grade III tumors. SLN biopsy is a reliable method to evaluate the status of the axillary lymph nodes. Imprint cytology can be used reliably where the facility of frozen section is not available. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]
Liver grafts from donors with central nervous system tumors: A single-center perspectiveLIVER TRANSPLANTATION, Issue 10 2009
Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 ± 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 ± 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204,1208, 2009. © 2009 AASLD. [source]
Correlation of Her-2/neu Gene Amplification with Other Prognostic and Predictive Factors in Female Breast CarcinomaTHE BREAST JOURNAL, Issue 4 2005
Reshma Ariga MD
Abstract: , The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p < 0.0003), ER (p = 0.0001) and PR (p < 0.0001) negative tumors, over-expression of MIB-1 (p < 0.0005) and high tumor grade (p = 0.0009), while size of the tumor (p = 0.08) and age of the patients (p = 0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification. [source]