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口腔扁平上皮癌におけるp53蛋白,熱ショック蛋白(HSP)70, Ki-67の発現に関する免疫組織化学的検討

By  Yasubumi MARUOKA,  Makio KOBAYASHI and  Hideki OGIUCHI


口腔扁平上皮癌患者70例の生体標本において,p53蛋白,熱ショック蛋白(HSP) 70の発現と,腫瘍細胞の増殖能をKi-67標識率を用いて免疫組織化学的に検索し,臨床病理学的因子,臨床経過との関連を検討した.P53癌抑制遺伝子異常は多くの臓器の癌細胞に高頻度に検出され,癌化およびその進展に他の遺伝子異常とともに寄与していると考えられている.またその産物である変異型p53蛋白は野生型p53蛋白に比べ構造が安定化し半減期が延長するため,過剰発現として免疫組織化学的に検出が可能である.この構造安定化の原因として変異型p53蛋白がHSP70と会合することが考えられている.p53蛋白の過剰発現は54.2%に認めたが,臨床病理学的因子,臨床経過との有意な相関は認めなかった.HSP70の発現は低分化なもの,核異型の高度なもの,核分裂像の多いものなど細胞増殖が活発な細胞で高頻度に認め,5年生存率はHSP70陽性群が陰性群に比べて有意に低下していた.細胞増殖能(Ki-67標識率)との関連性では低分化のもの,核異型が高度なもの,核分裂の多いものなどの細胞増殖が活発な細胞で,また臨床病期の進行した症例,頚部リンパ節転移を認めた症例でもKi-67標識率が有意に高値を示した.次にp53蛋白とHSP70の相関を検討すると,P53蛋白染色陽性の38例中31例がHSP70染色も陽性であり,変異p53蛋白とHSP70との相関が認められると考えた.p53蛋白,HSP70の同時発現と細胞増殖との関連では,p53蛋白,HSP70の同時陽性群では陰性群に比べKi-67標識率が有意に高値を示した.本研究の結果からp53蛋白,HSP70の免疫組織化学的発現とKi-67標識率を検索することは,口腔扁平上皮癌の生物的悪性度を知るうえで有用であり,さらに治療方針の決定や予後推定に際しての指標となり得ることが示唆された.We immunohistochemically analyzed the expression of the proteins p53, heat shock protein (HSP) 70 and Ki-67 labelling index (LI) in biopsy specimens from 70 patietns with oral squamous cell carcinoma (OSCC) and to analyze these findings in relation to the clinicopathologic parameters (CPP) and clinical course (CC) of these patients. Thirty eight (54.3%) of the 70 oral squamous cell carcinomas examined were positive for p53 protein. p53 protein expression was not correlated significantly with CPP and CC. Forty four (62.8%) of the 70 oral carcinomas were positive for HSP70. HSP70 positivity was significantly associated with a lower degree of histological differentiation (p<0.01), a high degree of nuclear polymorphism (p< 0.01), and a high frequency of mitosis (p<0.01). Kaplan-Meier's survival curves showed significantly shorter survival for HSP70-positive (41%) than the HSP70-negative patients (78%) according to the results of the Cox-Mantel test (p<0.01). Ki-67 LI was significantly associated with lower degrees of histological differentiation (p<0.01), markedly diffuse invasion of the tumor (p<0.01), high degrees of nuclear polymorphism (p<0.01), and high frequencies of mitosis (p<0.01). The index was also significantly high in patients in high clinical stages of cancer (p< 0.01) and patients with tumor metastasis to cervical lymph nodes (p<0.01). Coexpression of p53-HSP70 was found in 31 (81.6%) of the 38 p53 protein positive oral carcinomas. The mean value of Ki-67 LI was significantly higher in patients in whom both p53 protein and HSP70 were positive (39.1%) than in patients in whom both were negative (23.1%) (p<0.01). The results of this study suggest that an immunohistochemical examination for p53 protein and HSP70 and determination of the Ki-67 LI will be useful in assessing the biological malignancy level of OSCC, determining a therapeutic policy and predicting the prognosis of OSCC in a given case

Publisher: 東京女子医科大学学会
Year: 1996
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