Prognostic value of p53 expression in patients with stage I breast cancer


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The prognostic value of p53 nuclear expression in Stage 1 (T1N0M0) breast cancer was studied in 315 women treated in Russia (at the N.N.Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, and at the Clinic of the Russian Medical Academy of Postgraduate Education) in 1985 to 2009. An immunohistochemical assay for determining the expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 and the nuclear expression of p53 receptors was carried out at the Leiden University Medical Center. p53 nuclear expression was found in 14,7% of cases and statistically significantly correlated (p<0,05) with important prognostic factors, such as age less than 40 years; histologic type of infiltrating ductal cancer; high-grade cancer; ER- and PR-negative status; and HER2 overexpression. Analysis of overall and relapse-free survivals in the entire group of patients revealed no prognostic value (p>0,05) of p53 expression for the risk of further progression and death. It was suggested that the negative impact of p53 expression in the entire group might be compensated for by the positive role of adjuvant systemic therapy. Subgroup analysis showed that the patients with p53-positive tumors who did not receive any adjuvant drug treatment had the worst relapse-free and cancer-specific survival rates (p<0,05); this was not seen in the patients on adjuvant systemic treatment. Thus, p53 nuclear expression is a negative prognostic factor in Stage I breast cancer; adjuvant systemic therapy can appear to compensate for the unfavorable impact of the expression of this marker.

作者简介

I Kolyadina

ГБОУ ДПО РМАПО Минздрава РФ, Москва

Email: irinakolyadina@yandex.ru
канд. мед. наук, ассистент каф. онкологии

I Poddubnaya

ГБОУ ДПО РМАПО Минздрава РФ, Москва

д-р мед. наук, проф., чл.-кор. РАМН, зав. каф. онкологии

C Van de Velde

LUMC

президент ECCO, глава отд. хирургической онкологии LUMC

P Kuppen

LUMC

PhD, глава исследовательской лаборатории LUMC

G Liefers

LUMC

PhD, сотр. отд. хирургической онкологии LUMC

N Dekker-Ensink

LUMC

PhD, сотр. исследовательской лаборатории LUMC

E Bastiaannet

LUMC

PhD, сотр. отд. медицинской статистики LUMC

A Van As-Sajet

LUMC

сотр. исследовательской лаборатории LUMC

B Prinse

LUMC

сотр. исследовательской лаборатории LUMC

C Engels

LUMC

сотр. исследовательской лаборатории LUMC

R Van Vlierberghe

LUMC

сотр. исследовательской лаборатории LUMC

D Komov

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва

д-р мед. наук, проф., зав. отд-нием хирургической диагностики опухолей

A Karseladze

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва

д-р мед. наук, проф., зав. отд-нием патологической анатомии опухолей

V Ermilova

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва

д-р мед. наук, вед. науч. сотр. отд-ния патологической анатомии опухолей

Ya Vishnevskaya

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва

канд. мед. наук, науч. сотр. отд-ния патологической анатомии опухолей

G Frank

ФГБУ МНИОИ им. П.А.Герцена, Москва

д-р мед. наук, проф., зав. отд-нием патологической анатомии опухолей

S Banov

ГБОУ ДПО РМАПО Минздрава РФ, Москва

канд. мед. наук, врач-онколог клиники

参考

  1. Vousden K.H, Lane D.P. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8: 275–83.
  2. Petitjean A, Achatz M.I, Borresen-Dale A.L et al. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 2007; 26: 2157–65.
  3. Olivier M, Petitjean A, Marcel V et al. Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 2009; 16: 1–12.
  4. Olivier M, Langerød A, Carrieri P et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res 2006; 12: 1157–67.
  5. Lee D.S, Yoon S.Y, Looi L.M et al. Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi - ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early - onset breast cancer patients Breast Cancer Res 2012; 14 (2): R66.
  6. Evans D.G, Moran A, Hartley R et al. Long - term outcomes of breast cancer in women aged 30 years or younger, based on family history, pathology and BRCA1/BRCA2/TP53 status. Br J Cancer 2010; 102 (7): 1091–8.
  7. Courtois S, Verhaegh G, North S et al. N-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild - type p53. Oncogene 2002; 21: 6722–8.
  8. Bourdon J.C, Fernandes K, Murray-Zmijewski F et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev 2005; 19: 2122–37.
  9. Kandioler-Eckersberger D, Ludwig C, Rudas M et al. TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res 2000; 6: 50–6.
  10. Baker L, Quinlan P.R, Patten N et al. p53 mutation, deprivation and poor prognosis in primary breast cancer. Br J Cancer 2010; 102: 719–26.
  11. Bertheau P, Espié M, Turpin E et al. TP53 status and response to chemotherapy in breast cancer. Pathobiology 2008; 75: 132–9.
  12. Geisler S, Børresen-Dale A.L, Johnsen H et al. TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer. Clin Cancer Res 2003; 9: 5582–8.
  13. Bertheau P, Plassa F, Espié M et al. Effect of mutated TP53 on response of advanced breast cancers to high - dose chemotherapy. Lancet 2002; 360: 852–4.
  14. Bertheau P, Turpin E, Rickman D.S et al. Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose - dense epirubicin - cyclophosphamide regimen. PLoS Med 2007; 4: 90.
  15. Hiroko Yamashita, Mariko Nishio, Tatsuya Toyama et al. Coexistence of HER2 over - expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res 2004; 6: 24–30.
  16. Jakić-Razumović J, Corić M, Vrbanec D et al. The value of searching for additional prognostic factors in combination with Nottingham Prognostic Index inbreast carcinoma patients. Lijec Vjesn 2005; 127 (1–2): 3–7.
  17. Schmidt M.K, Tommiska J, Broeks A et al. Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients. Breast Cancer Res 2009; 11 (6): R89.
  18. Fang Q, Wang X.F. Correlation of CerbB-2 to Ki-67 and P53 expressions in hormone - independent breast cancer. Nan Fang Yi Ke Da Xue Xue Bao 2011; 31 (2): 380–2.
  19. Shirley S.H, Rundhaug J.E, Tian J et al. Transcriptional regulation of estrogen receptor - a by p53 in human breast cancer cells. Cancer Res 2009; 69 (8): 3405–14.

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