Lymphovascular Invasion in Breast Cancer Essay
Lymphovascular Invasion in Breast Cancer Essay
First described in 1979, and initially believed to be an oncogene, p53 was the first tumour suppressor gene to be identified. p53 functions to eliminate and inhibit the proliferation of abnormal cells, thereby preventing neoplastic development. Abrogation of the negative growth regulatory functions of p53 occurs in many, perhaps all, human tumours. The p53 signalling pathway is in ‘standby’ mode under normal cellular conditions.
Pros and cons to essay on p53 and Its Mutants in Tumor Cell Migration and Invasion
In 1979, the p53 protein was first identified. Its discovery was a product of research into viral etiology and the immunology of cancer. In 1979, two groups simultaneously reported similar results about the existence of a protein of around 55 kDa that bound to large T antigen in various types of cancerous cells. The p53 protein was named from its protein weighing 53 KDa. The protein was actually regarded as an oncogene at that time, as many tumors produce abundant levels of this protein—a phenomenon that was not observed in normal tissue, and ectopic expression of newly cloned TP53 cDNA was shown to cooperate with oncogenic Ras to transform primary cells in culture. However, it was soon recognized that p53 overexpression could transform cells and promote in vivo tumor growth.Lymphovascular Invasion in Breast Cancer Essay. This discrepant finding can be attributed to the use of different mutated versions of p53, which originally derived from tumor cells. In 1989, the first murine wild type TP53 cDNA was cloned and it was found that there was an absence of oncogenic activity.
Citations about essay on Lymphovascular Invasion and Histologic Grade Are Associated With Specific Genomic Profiles in Invasive Carcinomas of the Breast
Recent studies point to the significance of DNA copy number aberrations (CNAs) in the etiology of cancer with the number and complexity of these aberrations being indicative of overall prognosis [Bergamaschi A, Kim YH, Wang P, 2006]. CNA investigation may assist the identification of regions containing oncogenes and tumor suppressor genes. Grade III breast tumors frequently harbor gains at 3q and 5p, and 8q amplifications. More recently, a 19q12 amplification was detected, primarily associated with grade III breast tumors in estrogen-negative samples, which encompasses the CCNE1 gene, among others. Grade I tumors show less complex karyotypes with recurrent gain of 16p, as found in estrogen-positive tumors [Natrajan R, Lambros MB, 2009]. However, to the best of our knowledge, no study has investigated the genomic profile of CNAs related to the presence of LVI in breast carcinomas.
Conclusion to The p53 Pathway in Breast Cancer Essay
Obviously, mutant p53s, however, are very potent inducers of the metastatic phenotype. This owes, at least in part, to their ability to act via p63 to drive invasive-type migration. The contribution of TGF-β signaling and the trafficking of integrins and growth factor receptors to mutant p53-driven invasion suggests some interesting new candidates for antimetastatic drug development. Lymphovascular Invasion in Breast Cancer Essay.However, many questions remain as to how the elements of this pro-invasive program are connected to one another. In particular, we anticipate that the link between p63 and the cell’s migratory and trafficking machinery will provide fertile ground for those interested in targeting the metastatic process.
References
Natrajan R, Lambros MB, Rodríguez-Pinilla SM, Moreno-Bueno G, Tan DS, Marchió C, et al. Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res. 2009;15:2711–22.
Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-Boussard T, Lonning PE, et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosom Cancer. 2006;45:1033–40.
Hirose Y, Sasaki H, Abe M, Hattori N, Adachi K, Nishiyama Y, et al. Subgrouping of gliomas on the basis of genetic profiles. Brain Tumor Pathol. 2013;30:203–8. Lymphovascular Invasion in Breast Cancer Essay.
Published: 06 January 2006
Peritumoral lymphatic invasion is associated with regional lymph node metastases in prostate adenocarcinoma
Andres A Roma, Cristina Magi-Galluzzi, Melinda A Kral, Tao T Jin, Eric A Klein & Ming Zhou
Modern Pathology volume 19, pages392–398(2006)Cite this article
Abstract
Lymphangiogenesis, detected by antibodies specific for lymphatic endothelial cells, has been associated with regional lymph node metastases and poor prognosis in carcinomas of head and neck, breast and uterine cervix, but remains largely uninvestigated in prostate adenocarcinoma. We evaluated the lymphatic vessel density and lymphatic vessel invasion by prostate cancer cells in the intratumoral, peritumoral and normal prostate tissue compartments in cancer-bearing prostate glands and correlated them with lymph node metastases, Gleason score and other pathological parameters. Lymphatic vessels were detected by immunohistochemical stain using an antibody specific for the lymphatic endothelial cells (clone D2-40) on 33 radical prostatectomies. In all, 26 patients had lymph node dissection, and 14 of them had lymph node metastasis. The lymphatic vessel density and lymphatic vessel invasion were then recorded for each of the three compartments microscopically. Lymphatic vessel density in the intratumoral, peritumoral and normal prostate compartments was 0.91±0.80, 1.54±0.68 and 1.58±0.96/mm2, respectively. The intratumoral lymphatic vessel density was significantly lower than that of the peritumoral and normal prostate compartments, and the latter two were not significantly different. The lymphatic vessel density of the three compartments was not significantly different between cases with and without lymph node metastasis. The peritumoral lymphatic vessel density correlated inversely with the Gleason score. Lymphatic vessel invasion was present in significantly higher percentage of cases with lymph node metastasis (9/14, 62.3%), as compared to those without lymph node metastasis (1/12, 8.3%, P<0.01).Lymphovascular Invasion in Breast Cancer Essay. The peritumoral lymphatic vessel invasion had a better correlation with the presence of lymph node metastases than intratumoral lymphatic vessel invasion. There is no evidence of lymphangiogenesis in prostate adenocarcinoma. Peritumoral lymphatic vessel invasion correlates with regional lymph node metastases, suggesting that the peritumoral lymphatic vessels are functionally important and identification of lymphatic vessel invasion in this compartment implies a high probability of regional lymph node metastases.
Main
Metastasis is the hallmark of malignant neoplasms and the lymphatic system provides a key route for neoplastic dissemination.1, 2 Recent experimental evidence suggests that a wide variety of tumor cells can produce several lymphangiogenic factors, including vascular endothelial growth factor C and D (VEGF C and D), that promote the growth and remodeling of lymphatic vessels, a process termed lymphangiogenesis, through interaction with a cell surface receptor tyrosine kinase, vascular endothelial growth factor receptor 3 (VEGFR-3).2, 3, 4, 5, 6 Studies have also demonstrated that the expression of these lymphangiogenic factors correlate with metastatic spread of tumor cells to lymph nodes in many solid tumors.2, 3, 4, 5, 6 Furthermore, lymphangiogenesis detected by antibodies specific for lymphatic endothelial cells, has also been associated with regional lymph node metastases and poor prognosis in head and neck squamous cell carcinoma, melanoma, cervical and pancreatic cancers,7, 8, 9, 10, 11 although recent studies on breast cancer seem to contradict this finding.12, 13
Prostate adenocarcinoma is the most common noncutaneous malignancy and the second-leading cause of cancer death among men in the United States.14, 15 The presence of lymph node metastasis is a poor prognostic sign and indicates that the therapeutic modalities of curative intent, such as radical prostatectomy and radiation, have low probability of success in these patients.16 The molecular mechanism underlying lymphatic invasion and regional lymph node metastases are poorly understood in prostate cancer. Lymphovascular Invasion in Breast Cancer Essay. Several studies have found an increased expression of lymphangiogenic growth factors VEGF-C and D, and their receptor VEGFR-3 in prostate cancer cells and the increased expression of these genes correlated with advanced disease stage and lymph node metastases.17, 18, 19, 20 However, little is known whether the increased expression of these lymphangiogenic factors, in fact, leads to quantitative and/or qualitative alteration of lymphatic vessels in prostate adenocarcinoma or adjacent prostate tissue in prostate adenocarcinoma-bearing prostate glands. Only one recent study demonstrated lack of lymphangiogenesis in prostate adenocarcinoma.21 The same study also showed no correlation between the lymphatic vessel density and other pathological parameters.21
The objectives of our study were to confirm the lack of lymphangiogenesis in prostate adenocarcinoma by comparing the lymphatic vessel density in intratumoral, peritumoral and normal prostate compartments in prostate glands harboring prostate adenocarcinoma; to assess whether lymphatic vessels are functional, that is, whether invasion of these lymphatic vessels leads to lymph node metastasis; and to correlate lymphatic vessel density and lymphatic vessel invasion with other pathological parameters, including lymph node status, Gleason score, tumor volume, extraprostatic extension, seminal vesicle invasion and surgical margin status.
Materials and methods
Case Selection
A total of 33 radical prostatectomy specimens performed for prostate adenocarcinoma at the authors’ institution between 1998 and 2004 were included in this study. The clinical and pathological parameters of these cases were summarized in Table 1. In all, 26 patients had pelvic lymphadenectomy, 14 of whom had metastases in the pelvic lymph nodes involving a mean of 1.5 lymph nodes (range 1–3). Seven patients had no lymph node dissection. A single paraffin block containing prostate adenocarcinoma representative of the entire case (same Gleason score as the overall score of the case) was chosen for immunohistochemical detection of lymphatic vessels.
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Table 1 Clinical and pathological parameters of 33 prostate adenocarcinomas
Full size table
Detection of Lymphatic Vessels by Immunohistochemistry
Immunohistochemistry for lymphatic vessels was performed using a mouse monoclonal antibody reactive with an O-linked sialoglycoprotein found on lymphatic endothelium (clone D2-40, Signet Laboratories, Dedham, MA, USA).8, 22, 23 Briefly, the 5-μm tissue sections were antigen-retrieved in 0.1 M citrate buffer, pH6.0, in a pressure steamer for 15 min. The slides were then incubated sequentially with primary antibody (1:2000 dilution), biotinylated secondary antibody, avidin-peroxidase complex (Ventana, Tucson, AZ, USA) and chromogenic substrate diaminobenzidine. Lymphovascular Invasion in Breast Cancer Essay.
Quantification of Lymphatic Vessels and Lymphovascular Invasion
The three compartments of the prostate gland were defined as followings. The intratumoral compartment was defined as the area encompassing all the cancer glands present in the representative H&E section. The peritumoral compartment was a 1 mm-wide area around the intratumoral compartment. The area beyond the peritumoral compartment was defined as normal prostate compartment. The three compartments were marked on the H&E slides and their areas (mm2) were calculated using a 1 mm grid. The numbers of lymphatic vessels in these three zones were counted under the microscope using 10 × objectives. Any discrete D2-40 positive structure, regardless of the presence of lumens, was counted as one lymphatic vessel. Although basal cells of the benign prostate glands were also positive for D2-40, they could easily to be distinguished from lymphatic vessels (Figure 1). Lymphatic vessel density, defined as the number of lymphatic vessels per compartmental area, was calculated. Lymphatic vessel invasion, defined as prostate adenocarcinoma cells within the D2-40 positive structures, was also recorded for the three compartments. Lymphovascular Invasion in Breast Cancer Essay.
