Kosin Med J.  2012 Dec;27(2):119-125. 10.7180/kmj.2012.27.2.119.

Outcome of Ductal Carcinoma in Situ in Patients with or Without p53 Mutations

• Ryu DW
• Lee CH

• KMID: 2308520
• DOI: http://doi.org/10.7180/kmj.2012.27.2.119

Abstract

OBJECTIVES
p53 is a tumor suppressor gene and plays an important role in the etiology of breast cancer. The aim of this study is to clarify clinical significance of p53 in Ductal Carcinoma in situ (DCIS), and discuss about survival effect.
METHODS
The study subjects, 69 women with breast cancer, were a subset of patients operated from Jan 2005 to Dec 2006. We used a cutoff of 10% to distinguish between positive and negative p53 staining. The University of Southern California (USC)/Van Nuys Prognostic Index (VNPI) were compared with 2 categories of p53.
RESULTS
The positivity of p53 was found in 20 patients (29.0%) in DCIS. And negativity of p53 was found in 49 patients (71.0%). And 15 patients (21.7%) had a low USC/VNPI score, 42 patients (60.9%) intermediate and 12 patients (17.4%) a high score. The positivity of p53 was correlated with high USC/VNPI (P = 0.001). The univariate analysis for prognostic factors associated with Disease Free Survival (DFS) revealed that patients with p53 positivity show shorter Disease Free Survival (DFS) than patients with p53 negativity (P = 0.013) and USC/VNPI was also statistically significant (P = 0.030).
CONCLUSIONS
According to our study, p53 was associated with high USC/VNPI. These findings suggest that p53 can be used to classify DCIS into at least two subtypes with differing prognoses.

Keyword

Ductal carcinoma in situ; p53; Prognosis; VNPI

MeSH Terms

Breast Neoplasms
California
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Disease-Free Survival
Female
Genes, Tumor Suppressor
Humans
Prognosis

Figure

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  Fig. 1 Kaplan-Meier estimates for disease free survival according to USC/VNPI.

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  Fig. 2 2 Kaplan-Meier estimates for disease free survival according to p53.

Reference

1. Altintas S, Toussaint J, Durbecq V, Lambein K, Huizing MT, Larsimont D, et al. Fine tuning of the Van Nuys prognostic index (VNPI) 2003 by integrating the genomic grade index (GGI) : new tools for ductal carcinoma in situ (DCIS). Breast J. 2011. 17:343–351.

2. Adler EH, Sunkara JL, Patchefsky AS, Koss LG, Oktay MH. Predictors of disease progression in ductal carcinoma in situ of the breast and vascular patterns. Hum Pathol. 2012. 43:550–556.

3. Steinman S, Wang J, Bourne P, Yang Q, Tang P. Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast. Ann Clin Lab Sci. 2007. 37:127–134.

4. Al Mushawah F, Rastelli A, Pluard T, Margenthaler JA. Metastatic invasive breast cancer recurrence following curative-intent therapy for ductal carcinoma in situ. J Surg Res. 2012. 173:10–15.

5. Cutuli B, Lemanski C, Fourquet A, de Lafontan B, Giard S, Lancrenon S, et al. [Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. Bull Cancer. 2010. 97:301–310.

6. Furuya C, Kawano H, Yamanouchi T, Oga A, Ueda J, Takahashi M. Combined evaluation of CK5/6, ER, p63, and MUC3 for distinguishing breast intraductal papilloma from ductal carcinoma in situ. Pathol Int. 2012. 62:381–390.

7. Ballehaninna UK, Chamberlain RS. DCIS: Application of USC/Van Nuys Prognostic Index to assess postmastectomy recurrence: many hits and a few misses. Ann Surg Oncol. 2011. 18:Suppl 3. S272–S273.

8. Schmale I, Liu S, Rayhanabad J, Russell CA, Sener SF. Ductal carcinoma in situ (DCIS) of the breast: perspectives on biology and controversies in current management. J Surg Oncol. 2012. 105:212–220.

9. Chapman JA, Miller NA, Lickley HL, Qian J, Christens-Barry WA, Fu Y, et al. Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment. BMC Cancer. 2007. 7:174.

10. Kelley L, Silverstein M, Guerra L. Analyzing the risk of recurrence after mastectomy for DCIS: a new use for the USC/Van Nuys Prognostic Index. Ann Surg Oncol. 2011. 18:459–462.

11. Rajan PB, Scott DJ, Perry RH, Griffith CD. p53 protein expression in ductal carcinoma in situ (DCIS) of the breast. Breast Cancer Res Treat. 1997. 42:283–290.

12. Buonomo O, Orsaria P, Contino G, Varvaras D, Gioia A, Bonanno E, et al. Pathological classification of DCIS and planning of therapeutic management. Anticancer Res. 2009. 29:1499–1506.

13. Mylonas I, Makovitzky J, Jeschke U, Briese V, Friese K, Gerber B. Expression of Her2/neu, steroid receptors (ER and PR), Ki67 and p53 in invasive mammary ductal carcinoma associated with ductal carcinoma In Situ (DCIS) Versus invasive breast cancer alone. Anticancer Res. 2005. 25:1719–1723.

14. Goussia AC, Stefanou DG, Karaiossifidi EC, Agnantis NJ. DCIS histopathology from a historical perspective. Eur J Gynaecol Oncol. 2006. 27:282–285.

15. Liao N, Zhang GC, Liu YH, Li XR, Yao M, Xu FP, et al. HER2-positive status is an independent predictor for coexisting invasion of ductal carcinoma in situ of the breast presenting extensive DCIS component. Pathol Res Pract. 2011. 207:1–7.

16. Miki Y, Suzuki T, Sasano H. Intracrinology of sex steroids in ductal carcinoma in situ (DCIS) of human breast: comparison to invasive ductal carcinoma (IDC) and non-neoplastic breast. J Steroid Biochem Mol Biol. 2009. 114:68–71.

17. Nofech-Mozes S, Spayne J, Rakovitch E, Kahn HJ, Seth A, Pignol JP, et al. Biological Markers Predictive of Invasive Recurrence in DCIS. Clin Med Oncol. 2008. 2:7–18.

18. Di Saverio S, Catena F, Santini D, Ansaloni L, Fogacci T, Mignani S, et al. 259 Patients with DCIS of the breast applying USC/Van Nuys prognostic index: a retrospective review with long term follow up. Breast Cancer Res Treat. 2008. 109:405–416.

19. Idvall I, Ringberg A, Anderson H, Akerman M, Fernö M. Histopathological and cell biological characteristics of ductal carcinoma in situ (DCIS) of the breast-a comparison between the primary DCIS and subsequent ipsilateral and contralateral tumours. Breast. 2005. 14:290–297.

20. Kettritz U. Modern concepts of ductal carcinoma in situ (DCIS) and its diagnosis through percutaneous biopsy. Eur Radiol. 2008. 18:343–350.

21. Tot T. DCIS, cytokeratins, and the theory of the sick lobe. Virchows Arch. 2005. 447:1–8.