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Y. Hirai



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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-021 - Class III beta-tubulin expression in non-small cell lung cancer as a predictive marker for paclitaxel. (ID 2627)

      14:10 - 14:24  |  Author(s): Y. Hirai

      • Abstract

      Background
      Paclitaxel is one of the key drugs used in chemotherapy for the non-small cell lung cancer (NSCLC). Anti-microtubule agents, such as paclitaxel, stabilizes the microtubule polymer and prevents their breakdown. Data from the metastatic study suggest high tumor class III beta-tubulin (TUBB3) expression is a determinant of insensitivity to paclitaxel. To clarify whether TUBB3 is a true predictive marker for chemotherapy with paclitaxel, chemosensitivity was examined using an in vitro drug sensitivity assay.

      Methods
      Initially, 12 specimens were obtained to analyze the dose-response curve and to measure the median effective dose 50 (ED50) in the histoculture drug response assay (HDRA). The HDRA was perfomed for paclitaxel at several concentrations (minimum 0 μg/ml ,maximal 256μg/ml), in order to analyze the dose-response curves for individual patients. The value that was obtained from HDRA were directly applied for non-linear least square analysis using a formula of simplified dose-response curve. Subsequently, 41 surgically resected NSCLC specimens were applied to the HDRA and inhibition ratio at the concentration of 25μg/ml paclitaxel (IR25) was measured. H-scores were calculated by immunohistochemical staining. The patients comprised 26 male patients and 15 female patients. Mean age was 72±6.8. The specimens examined were 24 adenocarcinomas 17 squamous cell carcinomas.

      Results
      The mean (±SD) slope factor, ED50 and maximal response was 11.7±6.5, 24.6±7.73 μg/ml and 87.4±6.15% respectively. And the mean H-score was 50; (20-140). Among 12 specimens whose dose-response curve was obtained, the ED50 was higher than 25μg/ml in 5 (Resistant group) and lower in 7 (Sensitive group). The median H-score was significantly (p=0.0076) higher in Resistant group (240) than in Sensitive group (10). The mean IR25 was 53.8±26.6%. The median H-score in the specimens with IR25 above 50% (60, n=15) was significantly (p=0.0337) higher than that in specimens with IR25 under 50% (35, n=26).

      Conclusion
      Tumors with high TUBB3 levels exhibited chemoresistance to paclitaxel than tumors with low TUBB3 levels. HDRA revealed that TUBB3 expression is a true predictive factor for the response of paclitaxel in NSCLC.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-039 - Impact of Ki-67 labeling index as a predictive marker for chemotherapy in non-small cell lung cancer (ID 2532)

      09:30 - 09:30  |  Author(s): Y. Hirai

      • Abstract

      Background
      Ki-67 is a nuclear proliferation marker that reflects growth of tumor. Recently, the predictive implication of ki-67 labeling index (LI) for response to chemotherapy has been evaluated. Since St. Gallen International Expert Consensus in 2009, the ki-67 LI have been used one of factors that should help decide whether chemotherapy is given in breast cancer. In the present study, we examined the predictive value of ki-67 LI for chemotherapy for non-small cell lung cancer (NSCLC) patients using the histoculture drug response assay (HDRA).

      Methods
      Surgically resected fresh tumor specimens were obtained from 92 NSCLC patients at our institution from January 2007 to June 2011. The patients comprised 56 male patients and 36 female patients who ranged in age from 39 to 84 years (median= 73 years). The specimens examined were 57 adenocarcinomas, 26 squamous cell carcinomas, 4 adenosquamous carcinomas, 3 pleomorphic carcinomas and 2 other histological types. HDRA were used as an in vitro drug sensitivity test. HDRA technique was the same as we previously reported (JTCVS 133: 303-8, 2007). The inhibition rate of cisplatin and docetaxel were measured. Immunohistochemical staining for ki-67 was done and measured ki-67 LI. Relationships between ki-67 LI and the inhibition rate were examined using Spearman’s correlation coefficient test by rank test and chi-square test. Values of p<0.05 were considered to be significant.

      Results
      Immunohistochemical staining of ki-67 and the HDRA for cisplatin and docetaxel were successful in all specimens. Ki-67 LI was significantly correlated with the inhibition rate of cisplatin (rs=0.24, p=0.025) and docetaxel (rs=0.29, p=0.005) evaluated by HDRA. Ratio that have positive sensitivity for cisplatin in higher ki-67LI (ki-67 LI≧70) patients (52.6%) was significantly higher than that in lower ki-67LI (ki-67 LI≦30) patients (21.2%) (p=0.04). Ratio that have positive sensitivity for docetaxel in higher ki-67LI (ki-67 LI≧70) patients (40.0%) was significantly higher than that in lower ki-67LI (ki-67LI≦30) patients (10.8%) (p=0.025).

      Conclusion
      Our result revealed the ki-67 LI was the predictive marker for chemosensitivity in NSCLC. The high expression of ki-67 indicates positive sensitivity to cisplatin and docetaxel in patients with NSCLC.