MSH2蛋白は化学療法の有効性を予測する
（Abstract #: CRA7502）

ILAT：MSH2 DNA修復蛋白の少ない非小細胞肺がん患者は化学療法の有効性が高い
ILAT: Patients with non-small cell lung cancer lacking MSH2 DNA repair protein fare better with chemotherapy
国際アジュバント肺トライアル（International Adjuvant Lung Trial ：IALT）の解析の結果、腫瘍のMSH2蛋白レベルは外科的に除去された非小細胞肺がん（NSCLC）患者のシスプラチンベースの化学療法に対する長期の有効性を予測することが報告された、と第45回American Society of Clinical Oncology学会で発表された。腫瘍がMSH2を有する（"MSH2陽性"）NSCLC患者257人と腫瘍がMSH2を有さないあるいは腫瘍のMSH2レベルの低い（"MSH2陰性"）患者416人の全生存率を比較した。MSH2陰性の患者においては、シスプラチンを投与された患者の生存期間中央値は58ヵ月であったのに対し化学療法を受けなかった患者のそれは42ヵ月であった。MSH2陽性患者では、化学療法を施行された患者の全生存期間中央値は49ヵ月であったのに対し化学療法を受けなかった患者のそれは58ヵ月であった。次にこのスタディで明らかとなったことは、MSH2の的中率が、ERCCと呼ばれる過去に同定されたもうひとつのDNA修復関連蛋白のそれと同等であったことである。腫瘍内の両蛋白レベルの低い患者のうちシスプラチン治療を施行された者は化学療法を施行されなかった者と比較し生存期間が21ヵ月長かった（55ヵ月対34ヵ月、p=0.01）。研究者らは、シスプラチンベースの化学療法から得られる長期の有益性を予測するにはERCC1にMSH2レベルを組み合わせてもよいであろうと結論付けている。
Full Text

An analysis from the International Adjuvant Lung Trial (IALT) reports that tumor levels of the MSH2 protein predict long-term response to cisplatin-based chemotherapy among patients with surgically removed non-small cell lung cancer (NSCLC).

MSH2 is a protein that cancer cells use to repair DNA damaged by cisplatin. Researchers found that patients with no or low levels of the MSH2 protein respond better to treatment than patients with high levels.

A secondary finding of this study was that the predictive value of MSH2 was equal to that of a second, previously identified protein associated with DNA repair, called ERCC1. And when tumor levels of both ERCC1 and MSH2 are taken into account, researchers report they can further identify patients most likely to benefit from cisplatin-based chemotherapy.

"We have identified new and easily performed assays that can be used to predict response to chemotherapy in patients with non-small cell lung cancer by measuring tumor levels of two key proteins - ERCC1 and MSH2," said Pierre Fouret, M.D., Ph.D., professor at Institut Gustave Roussy (Villejuif, France) and Universite Pierre et Marie Curie (Paris, France) and the study's lead author. "This development is a step toward more personalized treatment for patients whose lung cancers have been surgically removed."

Cisplatin is commonly used as a postoperative treatment for NSCLC, but not all patients benefit. In this study, overall survival was compared between 257 patients with NSCLC whose tumors contained MSH2 ("MSH2-positive") and 416 whose tumors contained no MSH2 or low levels of this protein ("MSH2- negative"). Patients were then grouped by whether or not they underwent cisplatin-based adjuvant chemotherapy.

Adjuvant cisplatin-based chemotherapy increased overall survival among MSH2-negative patients, but did not benefit MSH2-positive patients. For MSH2-negative patients, median overall survival was 58 months for those who received cisplatin versus 42 months for those who did not receive chemotherapy. Among MSH2-positive patients, median overall survival was 49 months for those who received chemotherapy versus 58 months among those who did not.

Investigators also found that the predictive value of MSH2 and ERCC1 together was greater than either one alone. Patients with low tumor levels of both proteins who were treated with cisplatin-based chemotherapy lived 21 months longer than those who did not receive chemotherapy (55 months versus 34 months). The investigators concluded that MSH2 status may be combined with ERCC1 to predict long-term benefit from cisplatin-based chemotherapy.