Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy.
This study determined the prevalence and the prognostic value of the expression of microtubule components in tumors of 19 patients with non small cell lung cancer receiving taxane-based regimens. Patient samples were stained with antibodies directed against total beta tubulin, classes I, II and III beta tubulin isotypes, delta2 alpha tubulin, tau protein, and the P-gp protein involved in the classical multidrug resistance phenotype. All tumors were stained with pan-beta tubulin antibody and class I tubulin isotype. A majority of the tumor samples expressed class II and class III, although the percentage of positive cells varied significantly between tumors. delta2 alpha tubulin, tau protein and Pgp protein were found in only one tumor sample each. Progression-free survival was shorter (41 days) in patients whose tumors expressed high levels of class III tubulin isotype in comparison to patients with low levels (288 days, p = 0.02). There were 2 responses to chemotherapy among 9 patients (22%) with high levels of class III tubulin vs. 6 among 10 patients (60%) with low levels of expression (Fisher exact test: p = 0.11). These data suggest that high expression of class III tubulin by tumor cells is associated with poor prognosis in patients with NSCLC receiving a taxane-based regimen.
Dumontet
Charles
C
Inserm U453, Service d'hématologie, Centre hospitalier Lyon-Sud, 69495 Pierre-Bénite Cedex. charles.dumontet@chu-lyon.fr
Isaac
Sylvie
S
Souquet
Pierre-Jean
PJ
Bejui-Thivolet
Françoise
F
Pacheco
Yves
Y
Peloux
Nadine
N
Frankfurter
Anthony
A
Luduena
Richard
R
Perol
Maurice
M
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use*; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; C080625:taxane