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Expression of Class III ß-Tubulin Is Predictive of Patient Outcome in Patients with Non–Small Cell Lung Cancer Receiving Vinorelbine-Based Chemotherapy

Authors' Affiliations: ¹ Service de Médecine Interne, Hôtel Dieu, Hospices Civils de Lyon; ² Unité Institut National de la Sante et de la Recherche Medicale 590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Université Claude Bernard; ³ Service de Pneumologie, Hôpital de la Croix-Rousse; ⁴ Laboratoire d'Immunologie des Hémopathies, Hôpital Edouard-Herriot, Lyon, France; ⁵ Laboratoire d'Anatomopathologie and ⁶ Service de Pneumologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France; and ⁷ Laboratoire du Cytosquelette, Institut National de la Sante et de la Recherche Medicale U366, DBMS, Commissariat a l'Energie Atomique, Grenoble, France

Requests for reprints: Charles Dumontet, Unité Institut National de la Sante et de la Recherche Medicale 590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France. Phone: 33-4-78-77-7236; E-mail: charles.dumontet{at}chu-lyon.fr.

Purpose: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC).

Experimental Design: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins.

Results: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III ß-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III ß-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High 2 -tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II ß-tubulin, class III ß-tubulin, and 2 -tubulin levels, confirmed that class III ß-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012).

Conclusions: These findings suggest that a high level of expression of class III ß-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.

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