2012年12月24日月曜日

SYT–SSX遺伝子融合と滑膜肉腫の相関は100%??

融合遺伝子のなかで疾患関連性の高いもののひとつがSYT-SSX遺伝子融合である。発見当初は100%、今でも９割以上の滑膜肉腫に陽性であるという。ここまで高いと診断的価値も高いだろうな。特に滑膜肉腫が 珍しい場所にできる場合（肺、前立腺等々）は診断の一助になるものと考えられる。

N Engl J Med 1998; 338:153-160January 15, 1998

Original Article
SYT–SSX Gene Fusion as a Determinant of Morphology and Prognosis in Synovial Sarcoma

Akira Kawai, M.D., Ph.D., James Woodruff, M.D., John H. Healey, M.D., Murray F. Brennan, M.D., Cristina R. Antonescu, M.D., and Marc Ladanyi, M.D.

滑膜肉腫の形態および予後の決定因子としての SYT - SSX 遺伝子融合

SYT - SSX GENE FUSION AS A DETERMINANT OF MORPHOLOGY AND PROGNOSIS IN SYNOVIAL SARCOMA
Akira Kawai, and others





  • 背　景
    		• 滑膜肉腫は軟 組織肉腫の 10%を占め，主に二つの組織学的サブタイプ，二相性および単相性があり，それぞれ紡錘腫瘍細胞のバックグラウンドにおける腺上皮分化のあるものとないも のと定義される．染色体転座 t ( X; 18 ) ( p11; q11 ) に由来する特徴的な SYT - SSX 融合遺伝子は，ほぼすべての滑膜肉腫で検出可能であった．転座により，第 18 染色体からの SYT 遺伝子は，Xp11での二つの非常に相同な遺伝子，すなわち SSX1 または SSX2 のいずれかと融合する．SYT - SSX1および SYT - SSX2 は，異常転写制御因子として機能するように思われる．われわれは，SYT - SSX 融合遺伝子の形がこの肉腫患者の腫瘍形態および臨床転帰に及ぼす影響を明らかにしようと試みた．




  • 方　法
    		• 逆転写酵素ポリメラーゼ連鎖反応によって，滑膜肉腫 45 例 (単相性 33 人および二相性 12 人) の SYT - SSX 融合転写物を分析し，その結果を，関連する臨床および病理データと比較した．




  • 結　果
    		• SYT - SSX1 および SYT - SSX2 融合転写物はそれぞれ，腫瘍の 29 例 ( 64% ) および16 例 ( 36% ) に検出された．組織学的サブタイプ (二相性と単相性) と，融合転写物における SSX1 または SSX2 の関与とのあいだには有意な相関 ( p = 0.003 ) を認めた: 二相性の滑膜肉腫 12 例すべてが SYT - SSX1 融合転写物を有し，SYT - SSX2 陽性の腫瘍 16 例すべてが単相性であった．局所腫瘍を有する患者 39 人の Kaplan - Meier 法による分析では，SYT - SSX2 を有する患者 15 人は，SYT - SSX1 を有する患者 24 人より無転移生存率が有意に良好であることを示した (多変量解析により p = 0.03; 相対危険度，3.0 )．SYT - SSX 転写物のタイプと，年齢，性別，腫瘍の位置およびサイズ，診断時の転移の有無，または化学療法の有無，とのあいだには有意な相関を認めなかった．組織学的サブタイプ単独では予後的に重要ではなかった．




  • 結　論
    		• SYT -SSX 融合転写物のタイプは，滑膜肉腫の組織学的サブタイプおよび臨床症状のいずれとも相関する．SYT - SSX 融合転写物は滑膜肉腫の明確な診断マーカーであり，また重要な独立した予後情報を提供する可能性がある．

    N Engl J Med 1998; 338 : 153 - 60  をその後引用した217編の論文群

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