title: Bax, a predictive marker for therapeutic response to preoperative chemoradiotherapy in patients with rectal carcinoma.
abstract: In an attempt to improve local control and survival in patients with advanced rectal carcinoma, neoadjuvant chemoradiation therapy (CRT) has been increasingly used in patient management. However, a significant proportion of patients shows poor response to adjuvant CRT. Thus, the ability to predict CRT responsiveness in patients with rectal cancer would benefit effective management. Several molecular markers related to regulation of cell cycle, apoptosis, or DNA repair have been proposed as candidate predictors of therapeutic response to CRT, but, to date, none has been definitively proven to be predictive of CRT response. To evaluate the use of various molecular markers as predictors of the response to CRT in rectal carcinoma, we investigated immunohistochemical expressions of p53, p21 WAF1/CIP1 , Bcl-2, Bax, Ki-67, Ku-70, and 2 new candidate markers (histone deacetylase 1 and metabotropic glutamate receptor 4) in pretreatment biopsy samples of 130 rectal carcinomas. We further compared the expressions of these molecular markers with the pathological responses of the tumors after therapy. We found that Bax expression, among the markers studied, was exclusively related to tumor regression. Its expression was significantly higher in the complete response group as compared with the partial response group (54% versus 29%, P = .017). This result confirms that apoptosis plays an important role in tumor response to CRT and provides evidence that Bax may serve as a predictable molecular marker for chemoradiosensitivity in rectal carcinoma.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Gyeonggi 411-764, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Hyo Seong
authors.initials: HS
authors.lastname: Choi
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Dae Kyung
authors.initials: DK
authors.lastname: Sohn
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Joong-Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoon
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein