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Diane Provencher

Publications and source records attributed to Diane Provencher.

21 records · Page 2Linked to original sources
PubMed2002

Comparative analysis of loss of heterozygosity of specific chromosome 3, 13, 17, and X loci and TP53 mutations in human epithelial ovarian cancer.

We previously reported the identification of three minimal regions of deletion on the short arm of chromosome 3 (3p) in epithelial ovarian tumor specimens, suggesting that the inactivation of tumor-suppressor genes in these regions may be important in terms of ovarian tumorigenesis. Another previous study of ovarian cancer observed that allele loss of chromosome 179 was frequently found in ovarian tumors that also showed loss of heterozygosity (LOH) of chromosomes 3p, 13q, 17p, and Xp. In an independent study, we also reported a high frequency of LOH for selected chromosome 17 loci in high-grade and late-stage ovarian tumors. We have extended our LOH analysis of chromosome 3p to include 102 ovarian tumor specimens (29 and 73 samples were previously examined for LOH of chromosome 3p and 17 markers, respectively), using additional polymorphic markers, to assess the coordinate LOH of loci representing the three chromosome 3p minimal regions of deletions [von Hippel-Lindau syndrome (VHL), thyroid hormone receptor beta, and fragile histidine triad (FHIT)] and LOH of other important loci [tumor protein 53 (TP53), breast cancer 1 early onset (BRCA1), breast cancer 2 early onset, retinoblastoma 1, ornithine carbamoyltransferase, and androgen receptor] or somatic mutations in TP53. There was a significant association between LOH of any chromosome 3p marker and LOH of any chromosome 17 marker (P = 0.026). The frequency of LOH at the TP53 locus was higher in the group of samples that displayed LOH of a 3p marker (P = 0.019), as was the frequency of LOH at the BRCA1 locus (P = 0.014). LOH of chromosome 3p was noted in four specimens that did not display LOH of either the BRCA1 or the TP53 locus, indicating that LOH of these loci need not precede LOH of the chromosome 3p loci. We found a significant association between LOH of the VHL (3p25) locus and LOH of any chromosome 17 marker (P = 0.005), suggesting that there may be an important relationship, in the tumorigenesis of epithelial ovarian cancer, between a gene at 3p25 and a gene located on chromosome 17. Our results indicate that inactivation of p53 by somatic mutation is unlikely to be a prerequisite to chromosome 3p LOH, because we found no significant association between mutations in TP53 and LOH of the three chromosome 3p loci. The frequency of LOH at the FHIT locus at 3p14 increased significantly with advancing age at diagnosis (P = 0.018), as did the frequency of somatic TP53 mutations (P = 0.008).

Chromosomes, Human↗
PubMed2002

Expression profiles of 290 ESTs mapped to chromosome 3 in human epithelial ovarian cancer cell lines using DNA expression oligonucleotide microarrays.

We have investigated previously the utility of oligonucleotide expression microarray technology in an analysis of four spontaneously transformed epithelial ovarian cancer (EOC) cell lines, TOV-21G, TOV-81D, OV-90, and TOV-112D. Here, we examine the expression of 290 expressed sequence tags (ESTs) that map to human chromosome 3 in a primary culture derived from normal ovarian surface epithelium (NOSE), NOV-31, and the four spontaneously transformed EOC cell lines. One of these cell lines, OV-90, harbors a deletion of an entire chromosome 3p arm. Whereas the most aggressive cell lines (OV-90, TOV-112D, and TOV-21G) exhibited the highest levels of expression, assessed by the mean of expression values of all ESTs, OV-90 showed the lowest mean of expression of ESTs that map to the 3p arm in comparison with TOV-112D and TOV-21G. This difference in expression profile of 3p ESTs in OV-90 is also reflected in the ratio of expression of ESTs on 3p versus the 3q arm and in that the expression values of ESTs that map to 3p were more often lower than higher in OV-90 in two-way comparisons with NOV-31, TOV-21G, and TOV-112D. The loss of a 3p arm does not affect the pattern of differential expression in analyses based on the range of numeric expression values of each EST or fold differences in expression for each EST in comparison with NOV-31. However, 25 differentially expressed ESTs were identified on the basis of threefold differences in expression values between NOV-31 and any EOC cell line; and six of these ESTs were differentially expressed uniquely in OV-90. The investigation of these ESTs could facilitate the identification of novel chromosome 3 genes implicated in ovarian tumorigenesis.

Chromosome Mapping↗
PubMed2002

Breast cancer, pregnancy, and breastfeeding.

OBJECTIVE: The primary objective of this guideline is to provide Canadian physicians up-to-date, accurate information and recommendations regarding: i) impact of pregnancy and lactation on risk of breast cancer; ii) prognosis of breast cancer diagnosed during pregnancy and lactation; iii) risk of recurrence of breast cancer with the occurrence of subsequent pregnancies; iv) feasibility of breastfeeding and its impact on the prognosis of women with breast cancer. OPTIONS: This guideline reviews evidence on whether pregnancy and breastfeeding change the lifetime risk for breast cancer in women, and whether breast cancer diagnosed during pregnancy or during lactation has a different prognosis. It offers the clinician advice on the diagnostic options to help identify breast cancer in pregnancy and/or during lactation, and offers evidence-based recommendations in managing an ongoing pregnancy and/or lactation when treatment for breast cancer is being planned. It also offers recommendations to clinicians in counselling their patients regarding future pregnancy and future breastfeeding for women who have been treated for breast cancer. OUTCOMES: These guidelines should help physicians counsel patients using evidence-based recommendations. These recommendations may also improve the prognosis of patients diagnosed with breast cancer during pregnancy and lactation, or of those patients who had breast cancer and are contemplating future pregnancies. EVIDENCE: A Medline search was carried out for all publications from 1990 through 2000, in the English language, related to breast cancer and pregnancy in terms of diagnosis, prognosis, and treatment, as well as for breast cancer and breastfeeding, with particular focus on impact of treatment of breast cancer on lactation and prognosis of breast cancer after lactation. The authors submitted the manuscript for review to members of the Breast Disease Committee, who also validated the levels of evidence. The final manuscript was submitted to the SOGC Council for approval and dissemination. The levels of evidence for recommendations have been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS, AND COSTS: Canadian physicians will be able to counsel their patients on the impact of pregnancy and lactation on a woman's lifetime risk for breast cancer. Physicians and patients will be empowered to decide how to manage pregnancy and lactation when breast cancer is diagnosed in pregnancy, and to appreciate the ramifications of reproduction and breastfeeding after breast cancer. This guideline identifies areas where good evidence is lacking and advocates research in those areas. RECOMMENDATIONS: Women should be counselled regarding their risk for breast cancer and be informed that: 1. There is good evidence that there is a transient increase in risk of breast cancer in the first three to four years after delivery of a singleton baby (II-2B). Subsequently, their lifetime risk seems lower than that of women who remain nulliparous (II-2B). 2. There is good evidence that the risk for premenopausal breast cancer is reduced with lactation (II-2A). This protective effect seems to be best for women who had extended periods of breastfeeding during their lifetime (ll-2B). Women with familial risks could potentially benefit most from breastfeeding (II-2C). Since breast milk is the ideal nutrient for the newborn, and since breastfeeding is a modifiable risk factor, all women should be encouraged to breastfeed their children (II-2A). 3. All women should be encouraged to practice breast self-examination in pregnancy and during lactation (II-2B). Clinicians should screen all pregnant patients for breast cancer with thorough breast examination early in pregnancy (III-B). The clinician is advised to examine the breast in the postpartum period if the woman is not breastfeeding. The obstetrician is advised to examine the breast at any time in the postpartum period if the woman presents with breast symptoms (III-B). 4. Physicians should be encouraged to use ultrasltrasonography, mammography, needle aspiration, or breast biopsies to assess suspicious breast masses in pregnancy and during lactation, in the same timely fashion as for non-pregnant or non-lactating women (II-2A). Interruption of lactation during investigation is not necessary, nor is it recommended unless nuclear studies are entertained (III-B). 5. Once breast cancer is diagnosed, a multidisciplinary approach should be taken. This includes the obstetrician, surgeons, medical and radiation oncologists, and breast cancer counsellors (II-2A). 6. In early pregnancy, the patient should be counselled regarding the effect of proposed therapy on the fetus and on overall maternal prognosis. Termination of pregnancy should be discussed, but the patient should be counselled that prognosis is not altered by termination of pregnancy. Women should be advised that premature menopause may result from breast cancer treatments, especially if chemotherapy is given to patients who are past the age of 30. (II-2C) 7. Up until now, modified radical mastectomy was the cornerstone of surgical treatment of breast cancer during pregnancy. Adjuvant chemotherapy should be entertained and, if required, administered without delay. The patient should be counselled regarding the effect of chemotherapy on the fetus and/or the future reproductive potential of the patient (II-2B). In the third trimester, the risks and benefits of early delivery versus continuation of pregnancy, and the effect of chemotherapy on the fetus, should be addressed (II-2B). Women undergoing chemotherapy or tamoxifen treatment should not breastfeed (III-B). 8. Women treated for breast cancer and who wish to become pregnant should be counselled that pregnancy is possible and does not seem to be associated with a worse prognosis for their breast cancer (II-3C). However, they should be made aware that the evidence to support such advice is relatively poor. 9. Since most breast cancer recurrences appear within two to three years after initial diagnosis, patients should be advised to postpone pregnancy for three years (III-C). If a patient has axillary node involvement, the recommendation to defer pregnancy should be extended to five years, but this recommendation is based on opinion only (III-C). Prior to attempting pregnancy, a breast cancer survivor should be referred for a full oncologic evaluation. 10. There is no evidence that breastfeeding increases the risk of breast cancer recurring or of a second breast cancer developing, nor that it carries any health risk to the child. Women previously treated for breast cancer, who do not show any evidence of residual tumour, should be encouraged to breastfeed their children (III-B). VALIDATION: Level of evidence, quality of research in the recruited publications, and ensuing recommendations were reviewed and discussed by members of the SOGC Breast Disease Committee as well as by a member of the Gynaecological Oncology Committee. External reviewers with expertise in the area were also solicited for comments and criticism.

Breast Feeding↗