Class III β-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer.
BACKGROUND
Class III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy.


METHODS
We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients' response to chemotherapy, progression-free survival (PFS), and overall survival (OS).


RESULTS
In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS.


CONCLUSIONS
TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.
Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeonnam 519-763, Korea. ijchung@chonnam.ac.kr.
Jun-Eul
JE
Hwang
Ji-Yun
JY
Hong
Karham
K
Kim
Seung-Hun
SH
Kim
Won-Young
WY
Choi
Min-Jee
MJ
Kim
Sung-Hoon
SH
Jung
Hyun-Jeong
HJ
Shim
Woo-Kyun
WK
Bae
Eu-Chang
EC
Hwang
Kyung-Hwa
KH
Lee
Jae-Hyuk
JH
Lee
Sang-Hee
SH
Cho
Ik-Joo
IJ
Chung
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D012008:Recurrence; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D004268:DNA-Binding Proteins; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; C080625:taxane; C071447:ERCC1 protein, human; D004720:Endonucleases