© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 15, 1117,
August 1, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Women who experience preeclampsia during pregnancy have a reduced risk of breast cancer later in life. To investigate whether other placental abnormalities are also associated with a reduced risk of subsequent breast cancer, Cohn et al. (p. 1133) analyzed data from a cohort of nearly 4000 white women who had been pregnant at some point during the years 1959–1967 and for whom data were available on placental examinations and on subsequent development of invasive breast cancer. They found that smaller placentas, maternal floor infarction of the placenta, and increasing blood pressure during pregnancy all appeared to be independently associated with a decreased rate of maternal breast cancer. The authors note that investigation of the biologic basis for this association could ultimately pave the way for the development of prevention strategies that would benefit all women.
In an editorial, Hoover and Troisi (p. 1119) note that the suggested protective effects of certain pregnancy characteristics are provocative but caution that the results should still be viewed as hypotheses awaiting testing. If these findings are confirmed, they suggest that exploring the basic mechanisms that underlie them should be a high priority for researchers seeking to understand human breast carcinogenesis.
HER-2 Status of Primary and Metastatic Breast Cancers
If has been proposed that differences in HER-2 gene amplification and/or protein overexpression between primary breast tumors and their metastases may account for the fact that only 25% of women with HER-2-positive metastatic breast cancer respond favorably to treatment with trastuzamab (Herceptin). Simon et al. (p. 1141) used tissue microarray technology to compare HER-2 gene copy number and protein expression in four tissue samples from each of 196 lymph node-negative primary tumors and of 196 lymph node-positive primary tumors and three lymph node metastases derived from them. The authors found that individual breast tumors display little heterogeneity in HER-2 status and that the HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. The authors conclude that the high fraction of nonresponders to trastuzamab therapy cannot be explained by differences in HER-2 status between primary tumors and their metastases.
In an editorial, Thor (p. 1120) points out that Her-2 heterodimerization partners and activation of downstream signaling pathways may be of greater clinical relevance in determining response to Herceptin than differences in HER-2 status between primary and metastatic tumors. She recommends the global adoption of uniform standards for the laboratory testing of HER-2 status to resolve these issues.
Origin of Ovarian Tumors of Low Malignant Potential
Women with advanced-stage ovarian papillary serous adenocarcinoma often have peritoneal tumors that are monoclonal in origin. Gu et al. (p. 1147) asked whether the peritoneal tumors from women with ovarian papillary serous tumors of low malignant potential, or borderline tumors, are also monoclonal in origin. The authors assessed the clonality of 73 peritoneal and ovarian tumors from 18 patients. The authors found that the majority (86%) of peritoneal tumors of low malignant potential had different patterns of nonrandom X-chromosome inactivation compared to their ovarian tumors, suggesting that the tumors from the different ovarian and peritoneal sites arose independently. The authors conclude that peritoneal tumors associated with ovarian tumors of low malignant potential may arise independently from the primary tumor clones.
In an editorial, Gardner and Birrer (p. 1122) discuss the clinical, pathological, and molecular characteristics of ovarian tumors of low malignant potential, and they discuss how the the work of Gu et al. extends what is already known about these enigmatic tumors.
Screening Interval for PSA Tests
Although many men undergo annual serum prostate-specific antigen (PSA) screening tests to determine if they are at risk for prostate cancer, it has not been demonstrated that 1 year is the optimum interval between screening rounds. In this issue, Hoedemaeker et al. (p. 1153) report that a 4-year interval between screening rounds does not appear to compromise the detection of potentially curable cancers. The researchers compared histopathologic characteristics of screen-detected cancer on needle biopsy specimens obtained in an initial prevalence screen and in a second screen 4 years later. The amount of cancer in biopsy sets declined between the two rounds, as did the tumor grade. The authors suggest that large prostate cancers with high PSA values are effectively detected during a prevalence screen and that 4 years is too short for most large tumors to develop.
RBP1L1 Expression in Human Carcinomas and Normal Testis
Antibodies from cancer patients have been used to identify genes for tumor-associated proteins that generate immune responses in cancer patients. Cao et al. (p. 1159) have identified such an antibody and its corresponding antigenic epitope, gene, and protein, named retinoblastoma-binding protein-1-like protein-1 (RBP1L1). They sequenced the complete RBP1L1 complementary DNA and found that the derived protein sequence is closely related to other retinoblastoma-binding proteins. They localized the RBP1L1 antigenic epitope to the cytoplasm of cancer cells and detected high expression of its mRNA in various human cancers and normal testis, but expression was limited in other normal tissues. They conclude that RBP1L1 maybe a useful molecular marker because it is associated with many types of cancers.
NQO1 Deficiency and DMBA-Induced Cancer
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a phase II enzyme that catalyzes quinone detoxification and thus protects cells from quinones and its precursors, which can induce cancer. Quinones are produced during the metabolism of the polycyclic aromatic hydrocarbon benzo[a]pyrene. Mice lacking NQO1 genes (NQO1-/- mice) have been used to show that NQO1 protects mice from skin cancer induced by benzo[a]pyrene. Long et al. (p. 1166) used NQO1-/- mice to investigate whether NQO1 also protects against skin cancer induced by 7,12-dimethylbenz[a]anthracene (DMBA), which has methyl substituents that diminish primary quinone formation. They found that NQO1-/- mice were more susceptible to DMBA than their wild-type littermates. The authors suggest that NQO1 protects cells against DMBA-induced carcinogenesis, whether or not quinones are generated.
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