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N. Sueoka-Aragane
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-105 - SPARC, a Possible Predictive Marker to Albumin-Bound Paclitaxel (Nab-Paclitaxel) in Non-Small Cell Lung Cancer (ID 423)
09:30 - 09:30 | Author(s): N. Sueoka-Aragane
- Abstract
Background:
Anti-cancer agents to lung squamous cell carcinoma are limited compared to adenocarcinoma, and most novel therapeutic agents including molecular targeted therapy are indicated for adenocarcinoma not squamous cell carcinoma. Recently, it is reported that carboplatin plus albumin-bound paclitaxel (nab-paclitaxel) as first-line therapy in patients with advanced non-small cell lung cancer demonstrated a significantly higher overall response rate than carboplatin plus solvent-based paclitaxel (33% vs 25%, p=0.005) and in patients with squamous histology compared to non-squamous (41% vs 24%, p＜0.001) . Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in cell growth and angiogenesis through an interaction with extracellular matrix or cytokines. SPARC bound to albumin and they co-localized in cancer tissues, suggesting that SPARC plays an important role on higher tumor uptake of nab-paclitaxel. Expression of SPARC was correlated with prognosis in breast cancers and high SPARC stromal reactivity was correlated with tumor response to nab-paclitaxel in pancreatic cancers. nab-paclitaxel showed a good tumor response to lung squamous cell carcinoma, which is one of the most difficult cancers to be treated. In this study, we investigated the possibility of SPARC as a predictive marker for nab-paclitaxel.
Methods:
We studied the stromal SPARC reactivity and the association with clinicopathological characteristics in 200 non-small cell lung cancers using custom tissue microarray fabricated in our laboratory by immunohistochemical staining. SPARC stromal reactivity was defined as the percentage of reactive stromal area among the optical fields and scored as － ( less than 10%), ＋ (10%<, 50%≧) or ＋＋ (more than 50%). We also investigated the relationship between stromal SPARC reactivity and tumor response to nab-paclitaxel using small or surgical specimens obtained from advanced or recurrent lung cancer patients.
Results:
One hundred forty-five patients (72.5%) showed positive staining for stromal SPARC immunohistochemistry. The positivity of immunostaining was significantly higher in patients with Brinkman index (B.I) ≧ 400 (80/98, 82%) compared with in those with < 400 (65/102, 64%) (p = 0.01), in squamous cell carcinoma (26/29, 90%) compared with adenocarcinoma (107/155, 69%) (p = 0.03), and in vessel invasion positive (45/53, 85%) compared with vessel invasion negative (95/140, 68%) (p = 0.03). In contrast, positive staining of cytoplasmic or nucleus SPARC in cancer cells was rare (5 cases). We found that patients in stage I with high SPARC stromal reactivity had significantly shorter survival than patients with low SPARC stromal reactivity (log-rank p = 0.05). We also found that patients with high expression of stromal SPARC in small specimens such as TBLB or surgical specimens tend to response to nab-paclitaxel.
Conclusion:
Positive immunostaining of the stromal SPARC was more frequently observed in male smokers with squamous cell carcinoma , and good tumor response to nab-paclitaxel was correlated with high stromal SPARC reactivity. SPARC is a possible useful predictive marker for selecting nab-paclitaxel treatment.
