Abstract
Human mammary cancer is frequently associated with the erbB pathway, whereas 'spontaneous' mouse mammary tumor virus (MMTV)-induced mammary tumors are associated with the wnt-1 pathway. Many members of both pathways have been studied in genetically engineered mice. Using examples from the UCD Mutant Mouse Pathology Laboratory, we studied the characteristics of both pathways and found that they have unique, identifiable phenotypes. These observations are the foundation for pathway pathology. Members of the wnt1 pathway tend to form variations of the classical, MMTV-induced, type A, B and P tumors described by Dunn. Wnt1 tumors are expansile, surrounded by dense stroma, develop around central ducts, retain myoepithelial differentiation, and frequently have squamous metaplasia. Examples include the following: wnt1, wnt10b, APC1, GSK, CKII, B-Catenin, and FGF mice. In contrast, members of the erbB pathway are more likely to resemble human tumors, to be invasive, lose myoepithelial differentiation, form solid nodular asymetrical masses budding from individual ducts, have less stroma, and be less metaplastic. Examples include the following: erbB2, PyV-mT, mutants and bigenics of erbB and PyV-mT, src, and ras. Interestingly, GEM tumors initiated by nuclear factors do not tend to have the characteristics of either of these pathways. Examples: myc and lef1. These observations suggest that the principles of pathway pathology can be applied to human tumors of the breast and other organs. This work was supported by the DAAD (AR, individual grant), the State of California, BCRP JB-0014, and RO1CA89140 from NCI.
Highlights
Lymph node biopsy is important as a prognostic factor, and influences therapy
In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis
This study was undertaken to determine the effect of wound healing drainages and postsurgical sera obtained from breast carcinoma (BC) patients on proliferation of dormant BC cells and to assess the role of HER2 oncoprotein in this proliferation
Summary
Lymph node biopsy is important as a prognostic factor, and influences therapy. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment. Conclusion: Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy. We hypothesized that COX-2 expression was associated with that of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in human breast cancer. Conclusion: COX-2 expression is significantly associated with increased cellular proliferation and angiogenesis in invasive breast cancer. Recent studies have demonstrated that the sentinel node biopsy (SNB) is a reliable and minimally invasive method for determining the axillary node status in patients with breast cancer. Conclusion: Overexpression of episialin strongly inhibits fat secretion, and critically affects timing of involution of the lactating mammary gland
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