The use of molecular markers as a method to predict the response to neoadjuvant therapy for advanced stage rectal adenocarcinoma.

作者: Y. Edden , S. D. Wexner , M. Berho

DOI: 10.1111/J.1463-1318.2011.02697.X

关键词:

摘要: Aim  The response to combined neoadjuvant therapy for advanced stage rectal adenocarcinoma is predictive of outcome. In addition both clinical and pathological features, the expression a variety molecules may provide another method identifying tumour responsiveness pre-operative therapy. aim this study was evaluate several markers in apoptotic pathway as well Cox-2 vascular endothelial growth factor (VEGF) determine their ability predict therapy. Method  total, 152 patients with were treated followed by resection. Paraffin-embedded sections obtained before after assessed immunohistochemical staining Cox-2, VEGF, p53, p21, p27, Bax, BCL-2 apoptosis protease-activating 1 (APAF-1). These stains correlated regression grade, complete T-downstaging surgical specimen. Clinical data also collected. Data analysed using χ2 Spearman’s correlation tests. Results  Pathological seen 24.5% patients. Amongst apoptosis-associated markers, only APAF-1 found be significantly associated grade (P < 0.001), (P < 0.031) (P < 0.004). On multivariate analysis, independently good grade. contrast, overexpression VEGF pretreatment biopsies related less (P < 0.003) likelihood (P < 0.03). Conclusion  Immunohistochemical evaluation initial biopsy specimens cancer APAF-1, adenocarcinoma. Those an expected limited considered other investigational protocols.

参考文章(44)
María S Soengas, Paola Capodieci, David Polsky, Jaume Mora, Manel Esteller, Ximena Opitz-Araya, Richard McCombie, James G Herman, William L Gerald, Yuri A Lazebnik, Carlos Cordón-Cardó, Scott W Lowe, None, Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature. ,vol. 409, pp. 207- 211 ,(2001) , 10.1038/35051606
M. Dahlberg, B. Glimelius, L. Påhlman, Changing strategy for rectal cancer is associated with improved outcome British Journal of Surgery. ,vol. 86, pp. 379- 384 ,(2003) , 10.1046/J.1365-2168.1999.01040.X
George Theodoropoulos, W. E. Wise, A. Padmanabhan, B. A. Kerner, C. W. Taylor, P. S. Aguilar, K. S. Khanduja, T-Level Downstaging and Complete Pathologic Response After Preoperative Chemoradiation for Advanced Rectal Cancer Result in Decreased Recurrence and Improved Disease-Free Survival Diseases of The Colon & Rectum. ,vol. 45, pp. 895- 903 ,(2002) , 10.1007/S10350-004-6325-7
Jerry M Adams, Suzanne Cory, Apoptosomes: engines for caspase activation. Current Opinion in Cell Biology. ,vol. 14, pp. 715- 720 ,(2002) , 10.1016/S0955-0674(02)00381-2
Toshiaki Watanabe, Tsung-Teh Wu, Paul J. Catalano, Takashi Ueki, Robert Satriano, Daniel G. Haller, Al B. Benson, Stanley R. Hamilton, Molecular predictors of survival after adjuvant chemotherapy for colon cancer. The New England Journal of Medicine. ,vol. 344, pp. 1196- 1206 ,(2001) , 10.1056/NEJM200104193441603
Anne-Marie Mandard, Frédéric Dalibard, Jean-Claude Mandard, Jacques Marnay, Michel Henry-Amar, Jean-François Petiot, Alain Roussel, Jacques-Henry Jacob, Philippe Segol, Guy Samama, Jean-Marie Ollivier, Sylvie Bonvalot, Marc Gignoux, Pathologic Assessment of Tumor Regression After Preoperative Chemoradiotherapy of Esophageal Carcinoma. Clinicopathologic Correlations Cancer. ,vol. 73, pp. 2680- 2686 ,(1994) , 10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C
Fraser M Smith, William M Gallagher, Edward Fox, Richard B Stephens, Elton Rexhepaj, Emanuel F Petricoin 3rd, Lance Liotta, M John Kennedy, John V Reynolds, None, Combination of SELDI-TOF-MS and Data Mining Provides Early-stage Response Prediction for Rectal Tumors Undergoing Multimodal Neoadjuvant Therapy Annals of Surgery. ,vol. 245, pp. 259- 266 ,(2007) , 10.1097/01.SLA.0000245577.68151.BD
Inti Zlobec, Parham Minoo, Kristi Baker, David Haegert, Karim Khetani, Luigi Tornillo, Luigi Terracciano, Jeremy R. Jass, Alessandro Lugli, Loss of APAF-1 expression is associated with tumour progression and adverse prognosis in colorectal cancer. European Journal of Cancer. ,vol. 43, pp. 1101- 1107 ,(2007) , 10.1016/J.EJCA.2007.01.029
T.A. Rich, F. Sinicrope, C. Stephens, R. Meyn, N. Terry, M. Meistrich, J. Skibber, J. Ajani, K. Cleary, P. Lynch, 1031 Down staging of T3 rectal cancer after preoperative infusional chemoradiation is correlated with spontaneous apoptosis index and BCL-2 staining International Journal of Radiation Oncology Biology Physics. ,vol. 36, pp. 259- ,(1996) , 10.1016/S0360-3016(97)85542-3
Nobusada Shinoura, Shinya Sakurai, Akio Asai, Takaaki Kirino, Hirofumi Hamada, Co-transduction of Apaf-1 and caspase-9 augments etoposide-induced apoptosis in U-373MG glioma cells. Japanese Journal of Cancer Research. ,vol. 92, pp. 467- 474 ,(2001) , 10.1111/J.1349-7006.2001.TB01117.X