SPARC is a possible predictive marker for albumin-bound paclitaxel in non-small-cell lung cancer.
OBJECTIVE
Nanoparticle 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.


METHODS
We 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.


RESULTS
High 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.


CONCLUSIONS
Stromal 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.
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Kazutoshi
K
Komiya
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Tomomi
T
Nakamura
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Chiho
C
Nakashima
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Koichiro
K
Takahashi
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University; Japanese Red Cross Karatsu Hospital.
Hitomi
H
Umeguchi
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Naomi
N
Watanabe
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Akemi
A
Sato
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University; Department of Thoracic Surgery, Faculty of Medicine, Saga University, Saga, Japan.
Yuji
Y
Takeda
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Shinya
S
Kimura
Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University.
Naoko
N
Sueoka-Aragane
SPARC; lung cancer; nab-paclitaxel; predictive marker; squamous cell carcinoma