Skip to main content
Log in

Fluorescence in situ Hybridization and Immunohistochemical Analysis of p53 Expression in Endometrial Cancer: Prognostic Value and Relation to Ploidy

  • Gynecologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Endometrial carcinoma is the most common gynecological malignancy. Several molecular biological characteristics have been studied for their potential value in patient management.

Objectives

Our objectives were to compare p53 immunohistochemical expression with P53 gene status determined by fluorescence in situ hybridization (FISH) and to compare these characteristics with ploidy and with classical clinical and histological prognostic factors.

Materials and Methods

We reviewed stored specimens from 43 patients with endometrial cancer diagnosed in 1999–2004. P53 FISH and immunohistochemistry were performed, together with imaging cytometry to calculate DNA ploidy.

Results

Thirteen of the 43 endometrial carcinomas (30.2%) showed P53 loss of heterozygosity (LOH). P53 LOH correlated with the histological type (P = .03) and the histological grade (P = .004). Quantitative immunohistochemical expression of p53 protein correlated with the histological type (P = .0001). With a cutoff of 10% of p53-positive cells, p53 overexpression correlated with the histological type (P = .003) and grade (P = .0008). No relation was found between P53 LOH or immunohistochemical expression and the disease stage, the depth of myometrial invasion, lymph node status, lymphovascular space involvement, recurrence, or death from cancer. Nondiploid carcinomas showed deeper myometrial invasion than diploid carcinomas (P = .01). No relation was observed between ploidy and qualitative or semiquantitative p53 expression or P53 LOH.

Conclusion

In endometrial cancer, FISH analysis of P53 status adds no significant prognostic information compared with immunohistochemical p53 analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

FIG. 1.
FIG. 2.

Similar content being viewed by others

References

  1. Cook LS, Kmet LM, Magliocco AM, et al. Endometrial cancer survival among U.S. black and white women by birth cohort. Epidemiology 2006; 17:469–72

    Article  PubMed  Google Scholar 

  2. Rose PG. Endometrial carcinoma. N Engl J Med 1996; 335:640–9

    Article  PubMed  CAS  Google Scholar 

  3. Fisher B, Costantino JP, Redmond CK, et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 1994; 86:527–37

    Article  PubMed  CAS  Google Scholar 

  4. Mignotte H, Lasset C, Bonadona V, et al. Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. FNCLCC. Int J Cancer 1998; 76:325–30

    Article  PubMed  CAS  Google Scholar 

  5. Watson P, Vasen HF, Mecklin JP, et al. The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 1994; 96:516–20

    Article  PubMed  CAS  Google Scholar 

  6. May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 1999; 18:7621–36

    Article  PubMed  CAS  Google Scholar 

  7. Drane P, Bravard A, Bouvard V, et al. Reciprocal downregulation of p53 and SOD2 gene expression: implication in p53 mediated apoptosis. Oncogene 2001; 20:430–9

    Article  PubMed  CAS  Google Scholar 

  8. Mariani A, Sebo TJ, Webb MJ, et al. Molecular and histopathologic predictors of distant failure in endometrial cancer. Cancer Detect Prevent 2003; 27:434–41

    Article  PubMed  Google Scholar 

  9. Alkushi A, Lim P, Coldman A, et al. Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level. Int J Gynaecol Pathol 2004; 23:129–37

    Article  Google Scholar 

  10. Coronado PJ, Vidart JA, Lopez-Asenjo JA. P53 overexpression predicts endometrial carcinoma better than HER-2/neu overexpression. Eur J Obstet Gynecol Reprod Biol 2001; 98:103–8

    Article  PubMed  CAS  Google Scholar 

  11. Ragni N, Ferrero S, Prefumo F, et al. The association between p53 expression, stage and histological features in endometrial cancer. Eur J Obstet Gynecol Reprod Biol 2005; 123:111–6

    Article  PubMed  CAS  Google Scholar 

  12. Kounelis S, Kapranos N, Kouri E, et al. Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature. Mod Pathol 2000; 13:379–88

    Article  PubMed  CAS  Google Scholar 

  13. Davidoff AM, Humphrey PA, Iglehart JD, et al. Genetic basis for p53 overexpression in human breast cancer. Proc Natl Acad Sci USA 1991; 88:5006–10

    Article  PubMed  CAS  Google Scholar 

  14. Iggo R, Gatter K, Bartek J, et al. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 1990; 335:675–9

    Article  PubMed  CAS  Google Scholar 

  15. Hall PA, Lane DP. P53 in tumour pathology: can we trust immunohistochemistry? J Pathol 1994; 172:1–4

    Article  PubMed  CAS  Google Scholar 

  16. Soong R, Knowles S, Williams KE, et al. Overp53 expression protein is an independent prognostic indicator in human endometrial carcinoma. Br J Cancer 1996; 74:562–7

    PubMed  CAS  Google Scholar 

  17. Taskin M, Lallas TA, Barber HR, et al. bcl-2 and p53 in endometrial adenocarcinoma. Mod Pathol 1997; 10:728–34

    PubMed  CAS  Google Scholar 

  18. Erdem O, Erdem M, Dursun A, et al. Angiogenesis, p53, and bcl-2 expression as prognostic factors in endometrial cancer: comparison with traditional clinicopathological variables. Int J Gynecol Pathol 2003; 22:254–60

    Article  PubMed  Google Scholar 

  19. Zheng W, Cao P, Zheng M, et al. p53 overexpression and bcl-2 persistence in endometrial carcinoma: comparison of papillary serous and endometrioid subtypes. Gynecol Oncol 1996; 61:167–74

    Article  PubMed  CAS  Google Scholar 

  20. Ito K, Watanabe K, Nasim S, et al. Prognostic significance of p53 overexpression in endometrial cancer. Cancer Res 1994; 54:4667–70

    PubMed  CAS  Google Scholar 

  21. Williams JA Jr, Wang ZR, Parrish RS, et al. Fluorescence in situ hybridization analysis of Her-2/neu, c-myc and p53 in endometrial cancer. Exp Mol Pathol 1999; 67:135–43

    Article  PubMed  CAS  Google Scholar 

  22. Sandberg AA. Cancer cytogenetics for clinicians. Ca Cancer J Clin 1994; 44:136–59

    Article  PubMed  CAS  Google Scholar 

  23. Lim P, Aquino-Parsons CF, Wong F, et al. Low-risk endometrial carcinoma: assessment of a treatment policy based on tumor ploidy and identification of additional prognostic indicators. Gynecol Oncol 1999; 73:191–5

    Article  PubMed  CAS  Google Scholar 

  24. Santala M, Talvensaari-Mattila A. DNA ploidy is an independent prognostic indicator of overall survival in stage I endometrial endometrioid carcinoma. Anticancer Res 2003; 23:5191–96

    PubMed  Google Scholar 

  25. Benedet JL, Bender H, Jones H 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynaecologic cancers. FIGO committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000; 70:209–62

    Article  PubMed  CAS  Google Scholar 

  26. Kallioniemi A, Kallioniemi OP, Waldman FM, et al. Detection of retinoblastoma gene copy number in metaphase chromosomes and interphase nuclei by fluorescence in situ hybridization. Cytogenet Cell Genet 1992; 60:190–3

    Article  PubMed  CAS  Google Scholar 

  27. De Jong JS, Van Diest PJ, Baak JPA. Methods in laboratory investigation. Heterogeneity and reproducibility of microvessel counts in breast cancer. Lab Invest 1995; 73:922–6

    PubMed  Google Scholar 

  28. Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 1995; 147:9–19

    PubMed  CAS  Google Scholar 

  29. Matias-Guiu X, Catasus L, Bussaglia E, et al. Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 2001; 32:569–77

    Article  PubMed  CAS  Google Scholar 

  30. Tashiro H, Isacson C, Levine R, et al. P53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol 1997; 150:177–85

    PubMed  CAS  Google Scholar 

  31. Jovanovic AS, Boynton KA, Mutter GL. Uteri of women with endometrial carcinoma contain a histopathologic spectrum of monoclonal putative precancers, some with microsatellite instability. Cancer Res 1996; 56:1917–21

    PubMed  CAS  Google Scholar 

  32. Oehler MK, Brand A, Wain GV. Molecular genetics and endometrial cancer. J Br Menopause Soc 2003; 9:27–31

    Article  PubMed  Google Scholar 

  33. Inoue M, Okayama A, Fujita M, et al. Clinicopathological characteristics of p53 overexpression in endometrial cancers. Int J Cancer 1994; 58:14–9

    Article  PubMed  CAS  Google Scholar 

  34. Lukes AS, Kohler MF, Pieper CF, et al. Multivariable analysis of DNA ploidy, P53, and HER-2/NEU as prognostic factors in endometrial cancer. Cancer 1994; 73:2380–5

    Article  PubMed  CAS  Google Scholar 

  35. Leong AS-Y. Quantitation in immunohistology: fact or fiction? Appl Immunohistochem Mol Morphol 2004; 12:1–7

    PubMed  Google Scholar 

  36. McCluggage WG, Connolly LE, McGregor G, et al. A strategy for defining biologically relevant levels of p53 protein expression in clinical samples with reference to endometrial neoplasia. Int J Gynecol Pathol 2005; 24:307–12

    Article  PubMed  Google Scholar 

  37. Nenutil R, Smardova J, Pavlova S, et al. Discriminating functional and non functional p53 in human tumours by p53 and MDM2 immunohistochemistry. J Pathol 2005; 207:251–9

    Article  PubMed  CAS  Google Scholar 

  38. Wynford-Thomas D. P53 in tumour pathology: can we trust immunohistochemistry? J Pathol 1992; 166:329–30

    Article  PubMed  CAS  Google Scholar 

  39. Soussi T, Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nature Rev Cancer 2001; 1:233–40

    Article  CAS  Google Scholar 

  40. Soussi T, Kato S, Levy PP, et al. Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations. Hum Mutat 2005; 25:6–17

    Article  PubMed  CAS  Google Scholar 

  41. Ludwig RL, Bates S, Vousden KH. Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function. Mol Cell Biol 1996; 16:4952–60

    PubMed  CAS  Google Scholar 

  42. Semczuk A, Marzec B, Skomra D, et al. Allelic loss at TP53 is not related to p53 protein overexpression in primary human endometrial carcinomas. Oncology 2005; 69:317–25

    Article  PubMed  CAS  Google Scholar 

  43. Stewart RL, Royds JA, Burton JL, et al. Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein. Histopathology 1998; 33:440–5

    Article  PubMed  CAS  Google Scholar 

  44. Coleman RL, Schinck JC, Miller DS, et al. DNA flow cytometric analysis of clinical stage I endometrial carcinomas with lymph node metastases. Gynecol Oncol 1993; 50:20–4

    Article  PubMed  CAS  Google Scholar 

  45. Terada K, Mattson D, Goo D, et al. DNA aneuploidy is associated with increased mortality for stage I endometrial cancer. Gynecol Oncol 2004; 95:483–7

    Article  PubMed  CAS  Google Scholar 

  46. Lundgren C, Auer G, Frankendal B, et al. Prognostic factors in surgical stage I endometrial carcinoma. Acta Oncol 2000; 43:49–56

    Article  Google Scholar 

  47. Orbo A, Rydningen M, Straume B, et al. Significance of morphometric, DNA cytometric features, and other prognostic markers on survival of endometrial cancer patients in Northern Norway. Int J Gynecol Cancer 2002; 12:49–56

    Article  PubMed  CAS  Google Scholar 

  48. Biesterfeld S, Leitloff M, Rath W, et al. DNA image cytometry in the differential diagnosis of endometrial hyperplasia and adenocarcinoma. Analyt Quant Cytol Histol 2001; 23:123–8

    CAS  Google Scholar 

  49. Osmanagaoglu MA, Kadioglu S, Osmanagaoglu S, et al. The relationship between mutant p53 gene, DNA contents and conventional clinicopathological prognostic variables in cases with endometrial carcinoma. Eur J Gynaecol Oncol 2005; 26:64–70

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olivier Graesslin MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Graesslin, O., Chantot-Bastaraud, S., Lorenzato, M. et al. Fluorescence in situ Hybridization and Immunohistochemical Analysis of p53 Expression in Endometrial Cancer: Prognostic Value and Relation to Ploidy. Ann Surg Oncol 15, 484–492 (2008). https://doi.org/10.1245/s10434-007-9712-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-007-9712-1

Keywords

Navigation