Biomedical subjects

Irene Andrulis

Publications and source records attributed to Irene Andrulis.

8 recordsLinked to original sources

PubMed2006

Application of reliability coefficients in cDNA microarray data analysis.

Gene expression microarray technology has been widely used in areas such as human cancer research to identify molecular characteristics of sample specimens. The microarray study, however, is a very complicated procedure which involves numerous sources of variability that may be either systematic or random. Systematic variation is often eliminated by applying normalization procedures, but at present there are no standard criteria available to evaluate the performance of a particular normalization approach. In this paper, we propose a reliability-type coefficient as a criterion to assess the effectiveness of normalization procedures in eliminating systematic variation. Simulation studies show that this criterion performs reasonably well in a range of settings. The proposed method is illustrated using a subset of an ongoing microarray study of soft-tissue sarcoma.

Computer Simulation↗

PubMed2006

A genome wide linkage search for breast cancer susceptibility genes.

Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2.

Breast Neoplasms↗

PubMed2005

Prognostic factors affecting the natural history of node-negative breast cancer.

PURPOSE: We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer. PATIENTS AND METHODS: The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast. Paraffin-embedded tumour tissue was available for the majority of patients. The following factors were examined for their univariate and multivariate effects on time to recurrence outside the breast (DFI) and survival from breast cancer (DSS): age, weight, tumour size, estrogen receptor, progesterone receptor, histologic type, tumour grade, nuclear grade, lymphovascular invasion, overexpression of neu oncoprotein, DNA ploidy, % cells in S-phase, and adjuvant therapy. Multivariate analyses utilized a Cox model with a step-wise factor selection for the 260 patients with complete information. RESULTS: A worse prognosis was indicated when there was lymphovascular invasion (for DFI, p < 0.001; for DSS, p = 0.0046), high %S-phase (for DFI, p = 0.08; for DSS, p = 0.02), high tumour grade (for DFI, p = 0.02; for DSS, p = 0.03), and overexpression of neu oncoprotein (for DSS, p = 0.07). CONCLUSIONS: In our natural history investigation, two factors, lymphovascular invasion and tumour grade, are of particular interest since they may be readily incorporated into clinical practice. Overexpression of neu oncoprotein may also play a role in determining prognosis for women administered adjuvant systemic therapy.

Breast Neoplasms↗

PubMed2005

Invasive lobular carcinoma: to grade or not to grade.

Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain. The purpose of this study was to correlate histologic grade in invasive lobular carcinoma with known prognostic and predictive markers. All primary resections for invasive mammary carcinomas diagnosed in Mount Sinai Hospital, Toronto, between the years 1996 and 2002 were reviewed (n=1053). Of these cases, 50 were pure invasive lobular carcinoma (incidence 4.7%). The median age at diagnosis was 64 years. These tumors were graded using the Nottingham combined histologic grading system and analyzed for estrogen receptor, progesterone receptor, HER2/neu and E-cadherin expression. Tumor grade was correlated with tumor size (P=0.03), and the American Joint Committee on Cancer nodal status (P=0.05). Assessment of the individual components of grade showed that the mitotic score was highly correlated with tumor size (P=0.02), lymph node positivity (P=0.02) and overall American Joint Committee on Cancer stage (P=0.01). Estrogen receptor and progesterone receptor were highly expressed irrespective of the grade of tumor. HER2/neu protein overexpression and E-cadherin protein expression was absent in all invasive lobular carcinomas studied. We conclude that pure invasive lobular carcinoma is uncommon and occurs predominantly in postmenopausal women. Increasing tumor grade is correlated with median tumor size and the American Joint Committee on Cancer nodal stage, but not correlated with the expression of estrogen receptor, progesterone receptor, E-cadherin or HER2/neu protein overexpression.

Adult↗

PubMed2004

Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples.

Recent clinical trials have suggested that patients whose breast tumors overexpress HER2 may derive particular benefit from anthracycline-containing chemotherapy compared to that without anthracycline. It has been proposed that the HER2 gene amplification reported in these tumors might mask an underlying TOP2A gene amplification that occurs frequently and concurrently with HER2 amplification. Topoisomerase II alpha, encoded by TOP2A, is a direct molecular target of anthracycline drug action and is potentially useful as a predictive marker of response to anthracycline therapy for breast cancer. In this study, we examined whether TOP2A gene amplification is an appropriate marker for identifying breast tumors expressing high levels of topoisomerase II alpha. We determined topoisomerase II alpha protein expression by immunohistochemistry in 81 human breast tumors in relation to HER2 and TOP2A gene copy numbers analyzed by fluorescence in situ hybridization, histologic grade, cell proliferation fraction measured by MIB-1 expression, and HER2 protein expression determined by immunohistochemistry. The results showed no correlation between TOP2A gene copy number and topoisomerase II alpha protein expression levels in breast tumors, in contrast to the analogous situation for HER2 gene amplification and HER2 immunohistochemistry. Our results suggest that TOP2A gene amplification in breast tumors does not predict high expression of topoisomerase II alpha protein.

Antigens, Neoplasm↗

PubMed2004

Ethnicity, but not cancer family history, is related to response to a population-based mailed questionnaire.

PURPOSE: To determine if family history and ethnic background are factors affecting response to a mailed cancer family history questionnaire from the Ontario Familial Breast Cancer Registry. METHODS: Individuals diagnosed with primary invasive breast carcinomas (probands) were mailed a family history questionnaire, the first contact in a multi-stage process. This questionnaire obtained cancer family history and ethnicity data. After one month, a follow up telephone call was made to those who did not return this questionnaire and attempts were made to ask similar questions by telephone interview. Characteristics of those responding to the mailed questionnaire were compared to those who responded to the telephone interview only. RESULTS: 339 probands were included in this study: 242 returned a mailed version of the questionnaire; 57 completed the questionnaire over the phone. Cancer family history/genetic risk criteria was not significantly related to type of response. Probands identifying themselves as visible minorities were significantly less likely to respond to the mailed questionnaire than the telephone interview (11.6% vs. 22.8%, P=0.03). CONCLUSIONS: Having a family history of cancer did not appear to influence response to a mailed questionnaire, but those reporting an ethnic/racial background other than White were more likely to respond to a telephone interview.

Adult↗

PubMed2003

Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary.

Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.

Angiogenesis Inhibitors↗

PubMed2002

Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation.

BACKGROUND AND OBJECTIVES: Prior studies have shown that sarcoma growth can be stimulated by insulin-like growth factor-I (IGF-I). To extend this line of research, we carried out in vivo growth studies of primary human sarcoma in immunosuppressed control and IGF-I-deficient mice. METHODS: Human sarcoma specimens (one osteosarcoma and seven soft tissue sarcomas) were harvested in the operating room and implanted in immunosuppressed mice. Second-generation sarcomas were transplanted to control (GH replete lit/+ mice) and to experimental (GH/IGF-I-deficient lit/lit) animals. When tumors reached 1,000 mm(3) in one group, average tumor size was compared in the two groups. IGF-I receptor expression was measured by RT-PCR and IGF-I receptor binding sites were assayed by radiolabeled IGF-I. RESULTS: Five of eight sarcomas demonstrated reduced growth in the GH/IGF-I-deficient lit/lit animals. In four of the five sarcomas that demonstrated growth inhibition, IGF-R was elevated relative to placenta or a positive control cell line (MCF-7, which is known to be responsive to IGF-I in vitro and in vivo). In three of the five sarcomas that demonstrated growth suppression, IGF-R was elevated twofold after implantation in the experimental IGF-I-deficient animals. CONCLUSIONS: The GH-IGF axis may be an important stimulator of tumor growth in sarcomas. These experiments suggest that IGF suppression may inhibit sarcoma growth in vivo.

Animals↗