PP-9-3 Prognostic value of P21/WAF1 and P53 expression in breast carcinoma: An immunohistochemical study on 261 cases with long term follow up

Caffo, Orazio; Doglioni, Claudio; Veronese, Silvio; Bonzanini, Mariella; Morelli, Lucia; Palma, Paolo Dalla; Harris, Adrian L.; Barbareschi, Mattia

doi:10.1016/0959-8049(96)84269-9

Cited by 61 publications

(99 citation statements)

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“…Unlike others (Krajewski et al, 1995) bax did not contribute. The presence of p21 was associated with markers of a better prognosis and longer duration of survival for those receiving adjuvant hormonal therapy, which differs from that of Caffo et al (1996), who found it to be associated with shorter duration of survival, whereas Gohring et al (2001) found no relationship. Oestrogen receptor related to longer duration of survival but this was for the group receiving hormonal therapy, emphasising that any impact it has on survival relates to its value as a predictive marker of response.…”

Section: Discussionmentioning

confidence: 75%

“…p21 blocks progression of the cell cycle at G1/S and is involved in G2/M phase arrest (Dulic et al, 1998). Caffo et al (1996) concluded from a study of patients who received adjuvant therapy and had long-term follow-up that p21À/p53 þ tumours had the worst prognosis and that this pattern of expression may be of relevance for therapeutic response. However, Sjostrum et al (2000) found no relationship between expression of p21 and p53 and response to chemotherapy in advanced disease.…”

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confidence: 99%

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Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

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Established clinico -pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12 -127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P ¼ 0.001) and survivin (P ¼ 0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo-and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups.

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Section: Discussionmentioning

confidence: 75%

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confidence: 99%

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

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“…There were 13 patients whose tumours demonstrated p53 overexpression with concomitant under-expression of p21 WAF1/CIP1 , suggesting an abnormality in the p53 pathway. 37 Direct sequencing of p53 indicated that nucleotide changes were observed in 23 specimens, with 7 being polymorphic whereby despite nucleotide changes, there was no alterations in the amino acid. This resulted in a total of 11 missense mutations and 5 insertions or deletions, for a total number of 16 (21%) p53 abnormalities in these LNN breast cancer patients.…”

Section: P53 and P21 Waf1/cip1 Analysesmentioning

confidence: 99%

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Shi

Zhang

Pintilie

et al. 2003

Intl Journal of Cancer

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Recent studies demonstrate that abnormalities in PTEN may be one of the most frequent genetic events observed in human cancers. PTEN dysfunction leads to tumorigenesis through unopposed survival signals mediated via activated protein kinase B (PKB), which may also be associated with hormone-independence. We therefore investigated the relationship between PTEN-PKB and receptor status in human breast cancer. Several molecular variables, including immunohistochemical staining for PTEN, PKB (phosphorylated on ser473), p53 and p21 were evaluated. The p53 gene was sequenced from exons 2-11. Seventy-eight participants in a randomised breast cancer trial served as the cohort for our study. Twenty-eight of 77 (36%) patients' tumours demonstrated absent or reduced PTEN expression; 17 of 78 (22%) tumours over-expressed P-PKB. A significant inverse relationship was observed between reduced PTEN and increased P-PKB expression. Reduced PTEN also correlated with reduced ER or PR expression. None of the molecular variables correlated with survival. ER and PR negative tumours, however, experienced a significantly inferior disease-free survival than other ER/PR status tumours. Immunohistochemical analyses of ER expression in mammary carcinomas arising in PTEN heterozygous knockout mice did not demonstrate a reduction in ER immunoreactivity, in comparison to wildtype mice. Our data demonstrate that the PTEN-PKB pathway is abnormal in approximately 1 ⁄3 of lymph node negative breast cancer. Dysregulated PTEN-PKB was also associated with reduced ER/PR expression, but this does not appear to be a simple direct causal relationship. These observations support the contention that dysregulation in PTEN-PKB contributes to disease progression and hormone resistance of human breast cancer.

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“…The way in which bcl-2-protein over-expression has suppressed p21-protein expression is unclear. Upadhyay and colleagues demonstrated, in a study on breast epithelial cells, that suppression of p21 was at the transcriptional level, since bcl-2 over-expression was not associated with the p53-protein level itself, but to the p53-induced suppression of p21 mRNA expression (Upadhyay et al, 1995;Caffo et al, 1996). The data presented in our study are in agreement with the observations by Upadhyay et al (1995), although whether the same mechanism operates in the tumour tissue as in the cell lines is impossible to evaluate.…”

Section: Bcl-2- P21-and Er-protein Expressionmentioning

confidence: 99%

“…The fact that evaluation of p21-protein expression in tumour tissue is of importance has already been demonstrated (Caffo et al, 1996). In a study of 216 breast-carcinoma patients, these authors found that the presence of p21 protein in tumour cells was significantly associated with response to chemotherapy.…”

mentioning

confidence: 99%

Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53

et al. 1997

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PP-9-3 Prognostic value of P21/WAF1 and P53 expression in breast carcinoma: An immunohistochemical study on 261 cases with long term follow up

Cited by 61 publications

References 0 publications

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

Dysregulated PTEN‐PKB and negative receptor status in human breast cancer

Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53

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