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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000016
Original Articles

Serpin B3 Is Associated with Poor Survival after Chemotherapy and Is a Potential Novel Predictive Biomarker in Advanced Non–Small-Cell Lung Cancer

Urquhart, Gordon MRCP(UK)*†; Kerr, Keith M. FRCPath*‡; Nicolson, Marianne FRCP Edin; Loo, Peh Sun FRCPath; Sharma, Ravi FRCR; Shrimali, Raj FRCR; Petty, Russell D. PhD MRCP(UK)*†

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Abstract

Introduction:

In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non–small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.

Methods:

SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%–10% tumor cells positive, score 2 = 11%–50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.

Results:

Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29–2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥2, hazard ratio= 1.71; 95% confidence interval. 1.14–3.10; p = 0.002).

Conclusions:

SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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