Overview on Human Breast Cancer with Focus on Prognostic and Predictive Factors with Special Attention on the Tumour Suppressor Gene P53

Norberg, Torbjörn; Jansson, Tomas; Sjögren, S.; Mårtensson, Christoffer; Andréasson, I; Fjällskog, Marie-Louise; Lindman, Henrik; Nordgren, Hans; Lindgren, Anders; Holmberg, Lars; Bergh, Jonas

doi:10.3109/02841869609083980

Cited by 20 publications

(12 citation statements)

References 47 publications

(27 reference statements)

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“…Additional classical prognostic markers, including lymph node status, tumour size and stage, have also proven prognostic importance (Fitzgibbons et al, 2000). Many other potential prognostic markers have been identified, including p53, c-erbB2, BCL-2, CEA, CA15.3, CA27.29, cathepsin D and polyadenylate polymerase (Norberg et al, 1996;ASCO, (1998);Scorilas et al, 1999a,b;Fitzgibbons et al, 2000;Hamilton and Piccart, 2000). Markers may be predictive of treatment response e.g., HER-2 evaluation is useful for selection of patients for Herceptin therapy (Hamilton and Piccart, 2000).…”

Section: Discussionmentioning

confidence: 99%

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

et al. 2002

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Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 is newly discovered kallikrein gene that is located adjacent to KLK3 on chromosome 19q13.4. KLK15 has 41% similarity to KLK3 and the encoded protein, hK15, can activate proprostate specific antigen. We studied the expression of KLK15 by real-time quantitative reverse transcriptase -polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types. KLK15 expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and P=0.011) and overall survival (hazard ratio of 0.34 and P=0.009). When all other known confounders were controlled in the multivariate analysis, KLK15 retained its prognostic significance. Higher concentrations of KLK15 mRNA were found more frequently in node negative patients (P=0.042). No association was found between KLK15 expression and any other clinicopathological variable. Further, KLK15 is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis. KLK15 levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients. KLK15 is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor.

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Section: Discussionmentioning

confidence: 99%

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

et al. 2002

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“…The classical prognostic markers for breast cancer, including lymph node status, tumour size and stage, have proven clinical value (Fitzgibbons et al, 2000). Many other potential prognostic markers have been identified, including steroid receptors, epidermal growth factor receptor (EGFR), p53, c-erbB2, Bcl-2, CEQ, CA15.3, CA27.29, cathepsin D and polyadeylate polymerase (ASCO, 1998, Fitzgibbons et al, 2000Hamilton and Piccart, 2000;Nicholson et al, 1993Nicholson et al, , 1994Norberg et al, 1996;Scorilas et al, 2000). However, only hormone receptor status is recommended for routine use by the American Society of Clinical Oncology and the College of American Pathologists Consensus Statement (Fitzgibbons et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Human kallikrein gene 13 (KLK13) expression by quantitative RT–PCR: an independent indicator of favourable prognosis in breast cancer

et al. 2002

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Kallikreins are a group of serine proteases with diverse physiological functions. KLK13 (previously known as KLK-L4) is a novel kallikrein gene located on chromosome 19q13.4 and shares a high degree of homology with other kallikrein family members. Many kallikrein genes were found to be differentially expressed in various malignancies, and their regulation is controlled by steroid hormones in prostate and breast cancer cell lines. We studied the expression of KLK13 by quantitative reverse transcriptase -polymerase chain reaction in 173 patients with epithelial breast carcinoma. An optimal cutoff point equal to the 40th percentile was defined, based on the ability of KLK13 to predict disease-free survival. KLK13 values were then associated with other established prognostic factors and with disease-free survival and overall survival. Higher positivity for KLK13 expression was found in older, oestrogen receptor positive patients. In univariate analysis, KLK13 expression is a significant predictor of improved disease-free survival and overall survival (P50.001 and P=0.009, respectively). Cox multivariate analysis indicated that KLK13 was an independent prognostic variable in the subgroups of patients with Grade I -II tumours and in patients who were oestrogen receptor and progesterone receptor positive, and node positive. Hazard ratios derived from Cox analysis, related to disease-free survival and overall survival were 0.22 (P=0.001) and 0.24 (P=0.008), respectively, for the Grade I -II group; 0.36 (P=0.008) and 0.44 (P=0.038), respectively, for the node positive group and 0.36 (P=0.008) and 0.18 (P=0.008), respectively, for the oestrogen receptor positive group. The adjusted hazard ratio for progesterone receptor positive patients for disease-free survival was 0.25 (P=0.012). For patients in the node positive and oestrogen receptor positive subgroup (n=51) the adjusted hazard ratio was 0.25 (P=0.006) and for the node positive and progesterone receptor positive subgroup (n=46) the hazard ratio was 0.24 (P=0.008). Taken together, these data suggest that higher KLK13 expression in these subgroups of breast cancer patients is associated with an approximately 55 to 80% reduction in the risk of relapse or death. We conclude that KLK13 expression, as assessed by quantitative reverse transcriptase -polymerase chain reaction, is an independent favourable prognostic marker for breast carcinoma.

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“…There are sufficient data to postulate that these genetic aberrations are responsible for stepwise conversion from a normal to malignant cell [3][4][5]. Although many molecular biomarkers have been identified in human breast cancers, few of them, however, are recognized as candidate biomarkers related to disease prognosis and chemotherapy response [6].…”

Section: Discussionmentioning

confidence: 99%

“…Amplification and overexpression of cerbB-2 oncogene and mutations in p53 tumor suppressor genes were linked to various clinicopathological features in female breast cancer, including survival and chemotherapy response [6,7]. In addition, normal tissue responses within the tumor (e.g., neo-vascular formation) are essential for development and progression of primary tumor and acquisition of metastatic potential.…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer

et al. 2000

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Overview on Human Breast Cancer with Focus on Prognostic and Predictive Factors with Special Attention on the Tumour Suppressor Gene P53

Cited by 20 publications

References 47 publications

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

Human kallikrein gene 13 (KLK13) expression by quantitative RT–PCR: an independent indicator of favourable prognosis in breast cancer

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer

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