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The prognostic value of molecular biomarkers in tissue removed by curettage from FIGO stage 1 and 2 endometrioid type endometrial cancer

Published:November 03, 2008DOI:https://doi.org/10.1016/j.ajog.2008.07.020

      Objective

      To analyze the prognostic value of molecular biomarkers in curettages of endometrioid endometrial cancer pathologic FIGO stages 1 and 2.

      Study Design

      Population-based survival analysis in 258 patients of classical prognostic features and molecular biomarkers of cell cycle regulation, (anti)apoptosis, proliferation, squamous differentiation, and PTEN/Akt pathway.

      Results

      With 74 months median follow-up (range, 1-209), 24 (9.3%) patients had metastases develop. Pathologic FIGO stage 2B (6% of all cases) and age > 68 years had independent multivariate prognostic value. Many molecular biomarkers were prognostic, particularly cell-cycle regulators p16, p21, p27, p53, p63, and the antiapoptosis marker survivin (which mostly stains mitoses). The strong prognostic value of a multivariate model with survivin, p21, and p53 overshadowed all other prognosticators in pathologic FIGO 1 and 2A.

      Conclusion

      In pathologic FIGO stage 1 and 2A endometrioid endometrial cancer curettages, combined biomarkers survivin, p21, and p53 expression patterns are prognostically stronger than classical feature combinations.

      Key words

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      References

        • Announcements
        FIGO stages 1988 revision.
        Gynecol Oncol. 1989; 35: 125-127
        • Baak J.P.
        • Snijders W.
        • van Diermen B.
        • van Diest P.J.
        • Diepenhorst F.W.
        • Benraadt J.
        Prospective multicenter validation confirms the prognostic superiority of the endometrial carcinoma prognostic index in International Federation of Gynecology and Obstetrics stage 1 and 2 endometrial carcinoma.
        J Clin Oncol. 2003; 21: 4214-4221
        • van der Putten H.W.
        • Baak J.P.
        • Koenders T.J.
        • Kurver P.H.
        • Stolk H.G.
        • Stolte L.A.
        Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma.
        Cancer. 1989; 63: 1378-1387
        • Zaino R.J.
        • Silverberg S.G.
        • Norris H.J.
        • Bundy B.N.
        • Morrow C.P.
        • Okagaki T.
        The prognostic value of nuclear versus architectural grading in endometrial adenocarcinoma: a Gynecologic Oncology Group study.
        Int J Gynecol Pathol. 1994; 13: 29-36
        • Lundgren C.
        • Auer G.
        • Frankendal B.
        • Moberger B.
        • Nilsson B.
        • Nordstrom B.
        Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.
        Int J Gynecol Cancer. 2002; 12: 110-118
        • Salvesen H.B.
        • Iversen O.E.
        • Akslen L.A.
        Prognostic impact of morphometric nuclear grade of endometrial carcinoma.
        Cancer. 1998; 83: 956-964
        • Sorbe B.
        • Risberg B.
        • Thornthwaite J.
        Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial carcinoma.
        Int J Gynecol Cancer. 1994; 4: 94-100
        • Baak J.P.
        • Snijders W.P.
        • Van Diest P.J.
        • Armee-Horvath E.
        • Kenemans P.
        Confirmation of the prognostic value of the ECPI score (myometrium invasion, DNA-ploidy and mean shortest nuclear axis) in FIGO stage I endometrial cancer patients with long follow-up.
        Int J Gynecol Cancer. 1995; 5: 112-116
        • Hogberg T.
        • Fredstorp-Lidebring M.
        • Alm P.
        • et al.
        • Southern Swedish Gynecologic Oncology Group
        A prospective population-based management program including primary surgery and postoperative risk assessment by means of DNA ploidy and histopathology: adjuvant radiotherapy is not necessary for the majority of patients with FIGO stage I-II endometrial cancer.
        Int J Gynecol Cancer. 2004; 14: 437-450
        • Lindahl B.
        • Ranstam J.
        • Norgren A.
        • Willen R.
        Identification of high-risk groups in endometrial carcinoma stage I-II: a combination of DNA- and steroid receptor-measurements identifies early deaths from the disease.
        Anticancer Res. 1995; 15: 1095-1100
        • Kaku T.
        • Kamura T.
        • Kinukawa N.
        • et al.
        Angiogenesis in endometrial carcinoma.
        Cancer. 1997; 80: 741-747
        • Sivridis E.
        • Giatromanolaki A.
        • Anastasiadis P.
        • et al.
        Angiogenic co-operation of VEGF and stromal cell TP in endometrial carcinomas.
        J Pathol. 2002; 196: 416-422
        • Stefansson I.M.
        • Salvesen H.B.
        • Akslen L.A.
        Vascular proliferation is important for clinical progress of endometrial cancer.
        Cancer Res. 2006; 66: 3303-3309
        • Sivridis E.
        • Giatromanolaki A.
        • Anastasiadis P.
        • et al.
        • Tumor and Angiogenesis Research Group
        Angiogenic co-operation of VEGF and stromal cell TP in endometrial carcinomas.
        J Pathol. 2002; 196: 416-422
        • Fujimoto J.
        • Aoki I.
        • Khatun S.
        • Toyoki H.
        • Tamaya T.
        Clinical implications of expression of interleukin-8 related to myometrial invasion with angiogenesis in uterine endometrial cancers.
        Ann Oncol. 2002; 13: 430-434
        • Sung C.J.
        • Zheng Y.
        • Quddus M.R.
        • et al.
        p53 as a significant prognostic marker in endometrial carcinoma.
        Int J Gynecol Cancer. 2000; 10: 119-127
        • Ohkouchi T.
        • Sakuragi N.
        • Watari H.
        • et al.
        Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma.
        Am J Obstet Gynecol. 2002; 187: 353-359
        • Erkanli S.
        • Bolat F.
        • Kayaselcuk F.
        • Demirhan B.
        • Kuscu E.
        COX-2 and survivin are overexpressed and positively correlated in endometrialcarcinoma.
        Gynecol Oncol. 2007; 104: 320-325
        • Pallares J.
        • Martinez-Guitarte J.L.
        • Dolcet X.
        • et al.
        Survivin expression in endometrial carcinoma: a tissue microarray study with correlation with PTEN and STAT-3.
        Int J Gynecol Pathol. 2005; 24: 247-253
        • Gassel A.M.
        • Backe J.
        • Krebs S.
        • Schon S.
        • Caffier H.
        • Muller-Hermelink H.K.
        Endometrial carcinoma: immunohistochemically detected proliferation index is a prognosticator of long-term outcome.
        J Clin Pathol. 1998; 51: 25-29
        • Al Kushi A.
        • Lim P.
        • Aquino-Parsons C.
        • et al.
        Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.
        Mod Pathol. 2002; 15: 365-371
        • Li S.S.
        • Xue W.C.
        • Khoo U.S.
        • et al.
        Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis.
        Histopathology. 2005; 46: 307-313
        • Creasman W.T.
        Prognostic significance of hormone receptors in endometrial cancer.
        Cancer. 1993; 71: S1467-S1470
        • Sivridis E.
        • Giatromanolaki A.
        • Koukourakis M.
        • Anastasiadis P.
        Endometrial carcinoma: association of steroid hormone receptor expression with low angiogenesis and bcl-2 expression.
        Virchows Arch. 2001; 438: 470-477
        • Salvesen H.B.
        • Das S.
        • Akslen L.A.
        Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis.
        Clin Cancer Res. 2000; 6: 153-159
        • Nordengren J.
        • Fredstorp Lidebring M.
        • Bendahl P.O.
        • et al.
        High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer.
        Int J Cancer. 2002; 97: 379-385
        • Salvesen H.B.
        • Akslen L.A.
        Significance of tumor-associated macrophages, vascular endothelial growth factor and thrombospondin-1 expression for tumor angiogenesis and prognosis in endometrial carcinomas.
        Int J Cancer. 1999; 84: 538-543
        • Hecht J.L.
        • Mutter G.L.
        Molecular and pathologic aspects of endometrial carcinogenesis.
        J Clin Oncol. 2006; 24: 4783-4791
        • Kurman R.J.
        • Zaino R.J.
        • Norris H.J.
        Endometrial carcinoma: clinical and pathological features.
        in: Kurman R.J. Baustein's pathology of the female genital tract. 4th ed. Springer, New York1994: 448-449
        • Korner H.
        • Soreide K.
        • Stokkeland P.J.
        • Soreide J.A.
        Diagnostic accuracy of serum-carcinoembryonic antigen in recurrent colorectal cancer: a receiver operating characteristic curve analysis.
        Ann Surg Oncol. 2007; 14: 417-423
        • Stefansson I.M.
        • Salvesen H.B.
        • Akslen L.A.
        Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients.
        Int J Cancer. 2006; 118: 1227-1233
        • Salvesen H.B.
        • Iversen O.E.
        • Akslen L.A.
        Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study.
        J Clin Oncol. 1999; 17: 1382-1390
        • Ito K.
        • Sasano H.
        • Matsunaga G.
        • et al.
        Correlations between p21 expression and clinicopathological findings, p53 gene and protein alterations, and survival in patients with endometrial carcinoma.
        J Pathol. 1997; 183: 318-324
        • Ozkara S.K.
        • Corakci A.
        Significantly decreased P27 expression in endometrial carcinoma compared to complex hyperplasia with atypia (correlation with p53 expression).
        Pathol Oncol Res. 2004; 10: 89-97
        • Watanabe J.
        • Sato H.
        • Kanai T.
        • et al.
        Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus—correlation with proliferation and clinicopathological parameters.
        Br J Cancer. 2002; 87: 81-85
        • Takai N.
        • Miyazaki T.
        • Nishida M.
        • Nasu K.
        • Miyakawa I.
        Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma.
        Cancer Lett. 2002; 184: 105-116
        • Mutter G.L.
        • Lin M.C.
        • Fitzgerald J.T.
        • et al.
        Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers.
        J Natl Cancer Inst. 2000; 92: 924-930
        • Langley F.A.
        • Baak J.P.
        • Oort J.
        Diagnosis: error sources.
        in: Baak J.P. Manual of quantitative pathology in cancer diagnosis and prognosis. Springer, New York1991: 19-27
        • Skaland I.
        • Oevestad I.
        • Janssen E.A.
        • et al.
        Comparing subjective and digital image analysis HER2/neu expression scores with conventional and modified FISH scores in breast cancer.
        J Clin Pathol. 2008; 61: 68-71