Tau protein as a potential predictive marker in epithelial ovarian cancer patients treated with paclitaxel/platinum first-line chemotherapy

Journal of Experimental & Clinical Cancer Research

Cezary Szczylik²  Wojciech Kozlowski¹  Krystyna Zieniuk¹  Rafal Stec²  Bartlomiej Grala¹  Lubomir Bodnar²  Marta Smoter² 

[1] Pathology Department, Military Institute of Health Services in Warsaw, Szaserów Street 128, Warszawa, 04-141, Poland;Oncology Department, Military Institute of Health Services in Warsaw, Szaserów Street 128, Warszawa, 04-141, Poland

关键词: Chemotherapy;    Prognostic factor;    Predictive factor;    Ovarian cancer;    Tau protein;   

Others  :  825151
DOI  :  10.1186/1756-9966-32-25

 received in 2013-01-18, accepted in 2013-04-24,  发布年份 2013

【 摘 要 】

Background

The aim of the study was to evaluate predictive and prognostic significance of microtubule-associated protein Tau in epithelial ovarian cancer (EOC) patients treated with paclitaxel and platinum-based chemotherapy.

Methods

74 patients with EOC (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum chemotherapy were included in the retrospective analysis. Their formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for Tau protein, using semi-quantitative DAKO test. Tau expression was acknowledged as negative (0 and 1+) or positive (2+ and 3+). The correlation between Tau expression, progression free survival (PFS) and overall survival (OS) was evaluated. Statistical analysis included Kaplan-Meyer estimator, long rank test, Mann Whitney test and Cox proportional hazards model.

Results

25.7% (19/74) and 74.3% (55/74) of the patients were classified as Tau-negative and Tau-positive, respectively. Median PFS was 28.7 months for Tau-negative group and 15.9 months for Tau-positive group (p = 0.0355). In the univariate analysis 3-year OS in Tau-negative and Tau-positive groups was 80.2% and 52.4%, respectively (p = 0.0198). Low expression of protein Tau was associated with better OS, whereas an advanced stage at diagnosis, suboptimal surgery, serous histological type and resistance to first line chemotherapy were each correlated with worse OS (p <0,05). In multivariate analysis only resistance to first line chemotherapy remained significant (HR 22.59; 95% CI, 8.71-58.55; p <0.0001).

Conclusions

Negative tau protein seems to be both good prognostic factor and a predictor of response to paclitaxel/platinum-based chemotherapy in EOC patients.

【 授权许可】

   
2013 Smoter et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]McGuire WP, Hoskins WJ, Brady MF: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996, 334:1-6.
• [2]Piccart M, Bertrlsen K, James K: Randomized intergroup trial of cisplatin- paclitaxel versus cisplatin- cyclophosphamide in women with advanced epithelial ovarian cancer: three year results. J Natl Cancer Inst 2000, 92:699-708.
• [3]Amos LA, Löwe J: How Taxol stabilises microtubule structure. Chem Biol 1999, 6:65-9.
• [4]Rouzier R, Rajan R, Wagner P: Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 2005, 102:8315-20.
• [5]Kar S, Fan J, Smith MJ, Goedert M, Amos LA: Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO J 2003, 22:70-77.
• [6]Dye RB, Fink SP, Williams RC: Taxol- induced Flexibility of Microtubules and Its reversal by MAP-2 and Tau. J Biol Chem 1993, 268:6847-6850.
• [7]Robert M, Mathuranath PS: Tau and taupathies. Neurol India 2007, 55:11-16.
• [8]Pusztai L, Jeong JH, Gong Y: Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial. J Clin Oncol 2009, 27:4287-92.
• [9]Mimori K, Sadanaga N, Yoshikawa Y: Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment. Br J Cancer 2006, 94:1894-7.
• [10]Tanaka S, Nohara T, Iwamoto M: Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer. Cancer Chemother Pharmacol 2009, 64:341-6.
• [11]Pentheroudakis G, Kalogeras KT, Wirtz RM: Gene expression of estrogen receptor, progesterone receptor and microtubule-associated protein Tau in high-risk early breast cancer: a quest for molecular predictors of treatment benefit in the context of a Hellenic Cooperative Oncology Group trial. Breast Cancer Res Treat 2009, 116:131-43.
• [12]Rody A, Karn T, Gätje R: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast 2007, 16:86-93.
• [13]Gogas H, Pectasides D, Kostopoulos I: Paclitaxel and carboplatin as neoadjuvant chemotherapy in patients with locally advanced breast cancer: a phase II trial of the Hellenic cooperative oncology group. Clin Breast Cancer 2010, 10:230-7.
• [14]Fekete T, Rásó E, Pete I: Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples. Int J Cancer 2012, 131:95-105.
• [15]Shao YY, Kuo KT, Hu FC: Predictive and prognostic values of tau and ERCC1 in advanced breast cancer patients treated with paclitaxel and cisplatin. Jpn J Clin Oncol 2010, 40:286-93.
• [16]Han LY, Karavasilis V, Hagen T: Doubling time of serum CA125 is an independent prognostic factor for survival in patients with ovarian cancer relapsing after first-line chemotherapy. Eur J Cancer 2010, 46:1359-64.
• [17]Bae J, Lim MC, Choi JH: Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer. J Gynecol Oncol. 2009, 20:101-6.
• [18]Chi DS, McCaughty K, Diaz JP: Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 2006, 106:1933-9.
• [19]International Collaborative Ovarian Neoplasm Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 2002, 360:505-15.