摘要
目的：应用免疫组织化学技术对p73异构体(△Np73)在皮肤非黑素恶性肿瘤(鳞状细胞癌、基底细胞癌、鲍温病)、癌前病变(日光性角化病)、良性增殖性疾病(寻常型银屑病、脂溢性角化症)及正常人皮肤中的表达进行对照研究,同时与p53(在本文除非特别指出,均为突变型)在这些疾病中的表达进行对照。初步探讨△Np73在皮肤非黑素恶性肿瘤中的表达和意义,及其在肿瘤恶性程度及预后评估中的实际应用价值,以及△Np73与p53在良恶性增殖性疾病中表达的相关性。
方法：收集、整理昆明医学院第一临床学院皮肤科病理室及病理科保存的符合诊断标准的皮肤高、中、低分化鳞状细胞癌(SCC)60例及基底细胞癌(BCC)、鲍温病(BD)、日光性角化病(AK)、寻常型银屑病(PS)、脂溢性角化症(SK)各20例,并选取我科皮肤手术室及颌面外科手术切除的正常人皮肤(skin)10例。经过脱水、包埋、切片、染色等步骤,应用免疫组化技术对切片进行△Np73及p53的染色,最后评分,统计、分析各病种阳性病例数之间的差异以及△Np73、p53两个指标之间的相关性。
结果：p53在所有病种中均有阳性表达,但在皮肤非黑素恶性肿瘤(SCC、BCC、BD)和癌前病变(AK)中的表达阳性率明显超过良性增殖性疾病及正常人皮肤,差异有显著性(P<0.05),非黑素恶性肿瘤(SCC、BCC、BD)与癌前病变(AK)之间的表达阳性率无显著性差异(P>O.05)：△Np73在全部恶性肿瘤(SCC、BCC、BD)、部分良性增殖性病(PS)及癌前病变(AK)均有阳性表达,在部分良性增殖性病(SK)及正常人皮肤(skin)中无表达,其中SCC与AK的表达率明显高于其它病种,差异有统计学意义(P＜0.05),两者之间的差异无显著性差异(P>0.05);△Np73蛋白在各病种中的阳性表达率与发病部位(曝光部位与非曝光部位)、患者性别、年龄均无统计学差异(P>0.05)；△Np73和p53在SCC中的表达呈正相关(rs=0.348,P=0.007),在其它病种中的表达无相关性(P>0.05)。
结论：p53(突变型)阳性对诊断及鉴别良恶性增殖性疾病有一定意义,但在鉴别皮肤癌前病变与非黑素恶性肿瘤方面特异性较差；△Np73在SCC、AK的诊断中具有比较特异的诊断价值,尤其在与其他疾病的鉴别诊断中可能具有较强的实际应用价值,但对SCC病理分级无明显意义；△Np73蛋白的阳性表达率与患者的年龄、性别、发病部位无显著相关性；△Np73和p53在SCC中的表达具有相关性,提示两者在恶性肿瘤的发病中关系密切；联合应用△Np73和p53的可能对良恶性疾病的鉴别诊断更具有临床意义；△Np73与皮肤非黑素恶性肿瘤之间的复杂关系仍不十分清楚,尚需要更多的大样本量及具有详细临床资料的病例研究进一步阐明。
Objective To observe and contrast the expression of△N isoforms of p73(△Np73) and p53 (mutant type unless special explain)in cutaneous malignant tumors of non-melanin(squamous cell carcinoma, basal cell carcinoma and bowen disease), precancerous lesions(actinic keratosi), benign proliferating diseases(psoriasis、seborrheic keratosis) and nomal skin with immunohistochemistry. To discuss:the meaning of the expression of△Np73 in cutaneous malignant tumors of non-melanin; the actual value of△Np73 in malignant degree and prognosis of malignant tumors; The correlation of△Np73 and p53 in benign and malignant proliferating diseases.
Methods The patients who diagnosed pathologically in dermatology department and pathology department accord with the diagnosis standard as well, moderately poorly differentiated squamous cell carcinoma(SCC) 60 cases, basal cell carcinoma(BCC) 20 cases, bowen disease(BD) 20 cases, actinic keratosi(AK) 20 cases, psoriasis (PS) 20 cases, seborrheic keratosis(SK) 20 cases were collected, meanwhile, we also collected nomal skin 10 cases from operating room of our department and dentofacial surgery. After all cases were stained with immunohistochemistry,we analyzed the differentia of positive cases in all kinds of diseases and the correlation of△Np73 and p53.
Results All kinds of diseases were stained with p53. However,the positive proportion of p53 in cutaneous malignant tumors of non-melanin(SCC, BCC and BD) and precancerous lesions(AK) were significant higher than benign proliferating diseases(PS、SK) and nomal skin. The statistics difference was significant(P＜0.05). The difference between cutaneous malignant tumors of non-melanin(SCC, BCC and BD) and precancerous lesions(AK) was not significant(P＞0.05). All kinds of cutaneous malignant tumors of non-melanin(SCC, BCC and BD) and precancerous lesions(AK), some of benign proliferating diseases(PS) were stained with△Np73, others(SK,skin) were negative. the positive proportion of△Np73 in SCC and AK were significant higher than other diseases. The statistics difference was significant(P＜0.05). The difference between SCC and AK was not significant(P＞0.05). Both the statistics difference between the positive proportion of△Np73 in all kinds of diseases and anatomic sites (Exposure site and Non-exposure site), gender, age were not significant(P＞0.05).The positive correlation of△Np73 and p53 in SCC was observed(rs=0.348, P=0.007). There were no correlation of△Np73 and p53 in other diseases(P＞0.05).
Conclusion The expression of p53 is helpful to diagnosis and discrimination in benign and malignant proliferating diseases, but the specificity of diagnosis and discrimination in cutaneous malignant tumors of non-melanin and precancerous lesions is not good; The expression of△Np73 is specific in diagnosis and discrimination to other diseases of SCC and AK, but is not helpful to pathology classification of SCC; The correlation of△Np73 in all kinds of diseases and age, gender,anatomic sites were not observed; The relationship of△Np73 and p53 in SCC maybe tightness because of the correlation of expression of△Np73 and p53 is obviously; Combination of△Np73 and p53 is more useful than separateness in diagnosis and discrimination of benign and malignant proliferating diseases; The complicated relationship of△Np73 and cutaneous malignant tumors of non-melanin is not clear still, therefore, we need more cases research with large samples and detailed clinical data to explain it.
引文
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[1]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：1123-1125.
[2](美)麦基(Mckee,P.H.),(.英)卡隆赫(Calonje,E),(美)格兰特尔(Granter,S.R.)主编；朱学峻,孙建方主译.皮肤病理学：与临床的联系,第3版.北京：北京大学医学出版社,2006,12：1199-1209.
[3]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：1119-1121.
[4]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：1115-1117.
[5]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：577-578.
[6]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：759-772.
[7]赵辨.临床皮肤病学.第3版.南京：江苏科学技术出版社,2001：1111-1112.
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Trends Genet,2002,18(2):90-95.
[4]Scaruffi P, Casciano I, Masiero L, et al. Lack of p73 expression in mature B-ALL and identification of three new splicing variants restricted to pre B and C-ALL indicate a role of p73 in B cell ALL differentiation.[J]. Leukemia,2000,14(3):518-519.
[5]Fillippovich I, Sorokina N, Gatei M, et al. Transactivation-defi-cient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53[J]. Oncogene,2001,20(4):514-522.
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