ObjectivesNanoparticle albumin-bound paclitaxel (nab-paclitaxel) produced good tumor response in cases with lung squamous cell carcinoma, one of the most difficult cancers to treat. Secreted protein acidic and rich in cysteine (SPARC) binds to albumin, suggesting that SPARC plays an important role in tumor uptake of nab-paclitaxel. There is as yet no predictive marker for cytotoxic agents against non-small-cell lung cancer (NSCLC), and hence we believed that SPARC expression might be associated with tumor response to nab-paclitaxel.Patients and methodsWe studied stromal SPARC reactivity and its association with clinicopathological characteristics in 200 cases of NSCLC using a custom tissue microarray fabricated in our laboratory by immunohistochemical staining. We also investigated the relationship between stromal SPARC reactivity and tumor response to nab-paclitaxel using biopsy or surgical specimens obtained from advanced or recurrent lung cancer patients.ResultsHigh SPARC stromal reactivity (>50% of optical fields examined) was detected in 16.5% of cases and intermediate SPARC reactivity (10%–50%) in 56% of cases. High expression in cancer cells was rare (five cases). Stromal SPARC level was correlated with smoking index, squamous cell carcinoma, and vessel invasion. Furthermore, patients with high stromal SPARC reactivity in biopsy specimens such as transbronchial lung biopsy or surgical specimens tended to respond better to nab-paclitaxel.ConclusionStromal SPARC was detected by immunohistochemical staining in ∼70% of NSCLC cases, and good tumor response to nab-paclitaxel was correlated with high stromal SPARC reactivity. SPARC may be a useful predictive marker for selecting patients likely to respond favorably to nab-paclitaxel treatment.

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Monitoring of molecular markers is indispensable for deciding subsequent treatment after acquired resistance to molecular-targeted therapy. According to results using re-biopsy, EGFR T790M mutation and overexpression of hepatocyte growth factor (HGF) are major mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The aim of the present study was to assess whether quantification of HGF using peripheral blood in addition to detection of T790M with plasma DNA is useful for monitoring as an alternative to invasive re-biopsy. HGF levels in plasma were determined using ELISA and T790M mutation was detected using mutation-biased PCR and quenched probe system (MBP-QP). The median level of HGF in plasma at baseline was 140 pg/ml and was significantly higher in the advanced stage of cancer and in smokers and predicted poor survival as determined using 315 plasma samples from 225 lung cancer patients. T790M was detected with plasma DNA in 9 of 16 patients who acquired resistance to EGFR-TKIs and a greater than 1.5-fold elevation compared with pretreatment HGF levels was observed in 6 patients after acquired resistance. Eleven of 16 patients (69%) showed either HGF elevation or T790M in plasma samples, with both outcomes observed in 25% of patients; this is consistent with results based on re-biopsy reported from other laboratories. Considering these results, assessing HGF and T790M using peripheral blood could be useful for monitoring mechanisms of acquired resistance to EGFR-TKIs.

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