Prediction of response to docetaxel by quantitative analysis of class I and III beta-tubulin isotype mRNA expression in human breast cancers.
OBJECTIVE
The relationship of intratumoral mRNA levels of class I and III beta-tubulin isotypes with clinical response to docetaxel has been studied in breast cancer patients.


METHODS
Expression of class I and class III beta-tubulin mRNA levels was determined by a real-time PCR in breast cancer tissues obtained from 39 patients with locally advanced breast cancers (n = 26) or locally recurrent breast cancers (n = 13) before docetaxel treatment.


RESULTS
Class I beta-tubulin mRNA levels of responders [6.58 +/- 1.43 (x10(2)), mean +/- SE] were significantly (P = 0.002) lower than those of nonresponders [14.97 +/- 2.95 (x10(2))], and class III beta-tubulin mRNA levels of responders (1.38 +/- 0.40) were also significantly (P = 0.003) lower than those of nonresponders (7.43 +/- 2.77). Breast cancers were divided into four groups according to the expression status of class I and class III beta-tubulin isotype mRNA, i.e., the class I-high/class III-high group (n = 13), the class I-high/class III-low group (n = 7), the class I-low/class III-high group (n = 7), and the class I-low/class III-low group (n = 12). The class I-high/class III-high group showed a very low response rate (15%), whereas the class I-low/class III-low group showed a very high response rate (75%). The class I-high/class III-low group and the class I-low/class III-high group showed intermediate response rates of 57% and 43%, respectively.


CONCLUSIONS
These results demonstrate that high expression of class I and class III beta-tubulin isotype mRNA is significantly associated with docetaxel resistance, and determination of class I and class III beta-tubulin isotype mRNA levels would be useful in the prediction of response to docetaxel.
Hasegawa
Seiichi
S
Department of Surgical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Miyoshi
Yasuo
Y
Egawa
Chiyomi
C
Ishitobi
Makoto
M
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Monden
Morito
M
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017698:Postmenopause; D017697:Premenopause; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D014404:Tubulin / Q000096:biosynthesis*
D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D012313:RNA