P53 expression in breast cancer

Cattoretti, Giorgio; Rilke, F; Andreola, Salvatore; D'Amato, Lucia; Delia, Domenico

doi:10.1002/ijc.2910410204

Cited by 526 publications

(176 citation statements)

References 40 publications

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“…The proportion of cancers with p53 mutation (20%), p53 allele loss (41%), p53 mRNA expression (54%) and overexpression (28%) or p53 protein expression (32%) are similar to the reported series (Cattoretti et al, 1988;Davidoff, 1991;Iwaya, 1991;Kovach et al, 1991;Osborne et al, 1991;Runnebaum et al, 1991;Varley et al, 1991;Vojtesek et al, 1992;Andersen et al, 1993;Barnes, 1993;Friedrichs, 1993;Martinazzi, 1993;Thorlacius et al, 1993;Tsuda et al, 1993;Marks et al, 1994;Bergh et al, 1995;Borressen et al, 1995;Stenmark-Askmalm et al, 1995).…”

Section: Discussionsupporting

confidence: 74%

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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Summary Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41 %) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (1 7p1 3.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

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Section: Discussionsupporting

confidence: 74%

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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“…The identification of nuclear accumulation of p53 protein in 22% of the primary breast carcinomas in the present study is significantly less than the 57% reported by Thompson et al (1990) at the mRNA level, the 54% reported by Bartek et al, (1990a) using PAb 1801, 240, and 421, and the 45% reported by Cattoretti et al (1988) (Crawford et al, 1984;Davidoff et al, 1991b;Thor et al, 1992 (Bartek et al, 1990a). …”

Section: Discussioncontrasting

confidence: 72%

“…Several findings indicate that inactivation of TP53 is associated with a growth advantage in breast carcinoma: Accumulation of p53 protein has been reported to be associated with high grade tumours, increased levels of epidermal growth factor receptor (EGFR), presence of the proliferation associated antigen Ki67, advanced stage, metastatic spread, and low concentrations of oestrogen and progesterone receptors (Cattoretti et al, 1988;Thompson et al, 1990;Davidoff et al, 1991a;Varley et al, 1991;Mazars et al, 1992). Recent reports conclude that positive p53 immunostaining in primary tumour represents a prognostic parameter, suggesting that p53 protein accumulation might become clinically useful as an indicator of breast cancer aggressiveness (Iwaya et al, 1991;Ostrowsky et al, 1991;Varley et al, 1991;Isola et al, 1992;Mazars et al, 1992;Thor et al, 1992).…”

mentioning

confidence: 99%

Prognostic significance of TP53 alterations in breast carcinoma

Andersen

Holm²,

Nesland³

et al. 1993

Br J Cancer

155

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“…Like Pieteläinen et al (26), we found no correlation between p53 status and histologic grade, whereas two other groups reported higher p53 accumulation rates in poorly differentiated breast carcinomas (25,30). Although p53 is thought to be a determinant of genomic instability (33), we and others (24,26,27,31) did not find an association between abnormal p53 expression and DNA aneuploidy. Such a correlation was, however, described by Jacquemier et al (7).…”

Section: Discussionsupporting

confidence: 51%

Abnormal Expression of Cell Cycle Regulatory Proteins in Ductal and Lobular Carcinomas of the Breast

Geradts

Ingram

2000

Modern Pathology

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In a previous study, we demonstrated that the G1 cell cycle checkpoint in carcinomas of the breast is frequently abrogated by loss of p16, the product of the CDKN2/INK4A gene, and, to a lesser extent, by loss of pRB, the product of the retinoblastoma gene. The purpose of the present study was to determine whether other mechanisms of cell cycle deregulation exist in breast cancers which have retained RB and p16 function. Paraffin sections of 81 invasive breast carcinomas (49 ductal, 26 lobular, 6 mixed) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining results were correlated with the expression of p16 and pRB, and with a variety of pathological parameters and DNA ploidy. Twenty-five tumors (31%) accumulated (presumably mutant) p53 and 28 (35%) overexpressed cyclin D1; 7 carcinomas (not including any pure lobular cancers) abnormally expressed both proteins. p53 accumulation correlated with nuclear, mitotic, and overall grade, but not with tumor size, lymph node involvement, or DNA ploidy. Overexpression of cyclin D1 was not associated with any of the patho-biological variables. There was an inverse correlation between loss of p16 and high levels of p53, but not cyclin D1. The G1 cell cycle checkpoint, which is controlled by RB, cyclin D1, and p16, was abrogated in 65% of carcinomas, and only p53 was abnormal in an additional 17%. The number of abnormally expressed genes correlated with mitotic activity and overall tumor grade, but not with tumor histology, size, or nodal status, suggesting that cell cycle deregulation is an early event in breast tumorigenesis. Only 18% of the carcinomas showed a normal level of expression of the four genes tested, and p16 appeared to be the most common target of cell cycle deregulation. These data point to the importance of cell cycle regulatory protein abnormalities in human breast cancer.KEY WORDS: Breast cancer, Cell cycle, Cyclin D1, Immunohistochemistry, p16, p53, Pathology. Mod Pathol 2000;13(9):945-953It is generally accepted that several pathways need to be abrogated in the genesis of a malignant neoplasm. There is an increasing body of evidence that deregulation of one or more of the cell cycle checkpoints is among the most common abnormalities in human neoplasia. We have been particularly interested in the genes controlling the late G1 restriction point. Possibly the most critical component of the latter is pRB, the product of the retinoblastoma gene. Hyperphosphorylation, and hence inactivation of pRB is catalyzed by cyclin dependent kinases (CDKs), most notably CDK4 and 6. The CDKs are activated by binding to their respective cyclins, including cyclin D1 (1). They are inhibited by CDK inhibitors including p15 INK4B and p16 INK4A (specific for CDK4/6) and p21 WAF1 . The latter, in turn, is partially under the transcriptional control of p53 (2). We recently demonstrated that abnormal expression of the genes controlling the G1 restriction point is a very common occurrence in carcinomas ...

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P53 expression in breast cancer

Cited by 526 publications

References 40 publications

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Prognostic significance of TP53 alterations in breast carcinoma

Abnormal Expression of Cell Cycle Regulatory Proteins in Ductal and Lobular Carcinomas of the Breast

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