Immunohistochemical diagnosis and prognosis of small cell lung cancer: the search for new strategies

Irina Yakovtsova, O. Yanchevskyi, T. Chertenko, Andriy Kis, Andrii Oliyinyk
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Abstract

The aim: to find the optimal combination of immunohistochemical markers for differential diagnosis and prognosis of small cell lung cancer in small biopsy samples. Materials and methods. The tumor specimens were divided into 3 groups: 1) 25 biopsy samples of small cell lung cancer before treatment; 2) 25 samples of small cell lung cancer procured from autopsies of patients, who underwent chemotherapy; 3) 15 biopsy samples of other lung tumors histologically similar to SCLC. All tumor samples were formalin fixed and paraffin embedded (FFPE). Immunohistochemical study performed with 5 primary antibodies: CD56, p16ink4A, TTF-1, CD117, Ki-67. Results. TTF-1 was positive in all small cell lung cancer, lung adenocarcinomas and atypical carcinoids. Expression of CD56 was positive in 100 % of tumors from 1st group and 92 % of these tumors had more than 25 % of positive tumor cells. Expression of p16ink4A was significantly higher in 1st group than in the 3rd one (р<0,001). The stepwise logistic regression was used for finding the best markers for differential diagnosis of small cell lung cancer in small biopsy samples. The next combination of markers was chosen: TTF-1/CD56 (score 2–4)/p16 ink4A/CD117 (sensitivity – 80 %; specificity – 86.67 %; р<0,001) where “score 2–4” means expression of CD56 more than in 25 % tumor cells. Expression of Ki-67 was higher in the 2nd group compared with the 1st one (р<0,001). Conclusion. Evaluation of p16 expression can be used as additional marker for differential diagnosis of small cell lung cancer. The following combination of markers: TTF-1/CD56 (score2-4)/p16 ink4A/CD117 could be useful in diagnosis of small cell lung cancer in small biopsy samples and in the choice of targeted chemotherapy. The further study in paired tumor samples of small cell lung cancer before and after chemotherapy is required to prove the significance of changes in expression of Ki-67, CD56, CD117 and p16ink4A
小细胞肺癌的免疫组化诊断与预后:寻找新策略
目的:寻找小细胞肺癌活检样本中免疫组化标志物鉴别诊断和预后的最佳组合。材料和方法。肿瘤标本分为3组:1)治疗前小细胞肺癌活检标本25例;2) 25例接受化疗的小细胞肺癌患者的尸检样本;3)其他组织学上与SCLC相似的肺肿瘤活检标本15例。所有肿瘤标本均采用福尔马林固定石蜡包埋(FFPE)。用5种一抗CD56、p16ink4A、TTF-1、CD117、Ki-67进行免疫组化研究。结果。TTF-1在所有小细胞肺癌、肺腺癌和非典型类癌中均呈阳性。CD56在第一组100%的肿瘤中呈阳性表达,其中92%的肿瘤细胞阳性表达率超过25%。p16ink4A在第1组的表达明显高于第3组(p < 0.01)。采用逐步logistic回归方法寻找小细胞肺癌活检样本鉴别诊断的最佳标志物。选择下一个标记物组合:TTF-1/CD56(评分2-4)/p16 ink4A/CD117(灵敏度- 80%;特异性- 86.67%;其中“评分2-4”表示CD56的表达高于25%的肿瘤细胞。Ki-67在第二组的表达明显高于第一组(p < 0.01)。结论。p16的表达可作为小细胞肺癌鉴别诊断的附加指标。TTF-1/CD56 (score2-4)/p16 ink4A/CD117组合可用于小细胞肺癌活检样本的诊断和靶向化疗的选择。需要在化疗前后的小细胞肺癌配对肿瘤样本中进一步研究,以证明Ki-67、CD56、CD117和p16ink4A表达变化的意义
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