The efficiency of Ki-67 expression and CT imaging features in predicting the degree of lung adenocarcinoma invasion_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Xiaowen ¹ , ZHAO Ziwei ² , YE Guanzhi ³ , FENG Yihui ³ , ZHU Xiaolei ³ ,  GENG Guojun ³ ,  JIANG Jie ³

1. Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, P. R. China;
2. Department of Pathology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, P. R. China;
3. Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian, P. R. China;

Corresponding author：

GENG Guojun, Email: ggj622@126.com; JIANG Jie, Email: jiangjie06@126.com

Keywords：

Pulmonary nodules; Ki-67; immunohistochemistry; diagnosis; imaging features; lung cancer

DOI：

10.7507/1007-4848.202203046

Video：

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Objective To explore the efficiency of Ki-67 expression and CT imaging features in predicting the degree of invasion of lung adenocarcinoma. Methods The clinical data of 217 patients with pulmonary nodules, who were diagnosed as suspicious lung cancer by multi-disciplinary treatment clinic of pulmonary nodules in our hospital from September 2017 to August 2021, were retrospectively analyzed. There were 84 males and 133 females, aged 52 (25-84) years. The patients were divided into two groups according to the infiltration degree, including an adenocarcinoma in situ and microinvasive adenocarcinoma group (n=145) and an invasive adenocarcinoma group (n=72). Results There was no statistical difference in the age and gender between the two groups (P>0.05). The univariate analysis showed that CK-7, P63, P40 and CK56 expressions were not different between the two groups (P=0.172, 0.468, 0.827, 0.313), while Napsin A, TTF-1 and Ki-67 expressions were statistically different (P=0.002, 0.020, <0.001). The multivariate analysis showed that Ki-67 expression was statistically different between the two groups (P<0.001). Ki-67 was positively correlated with malignant features of CT images and the degree of lung adenocarcinoma invasion (P<0.05). Ki-67 and CT imaging features alone could predict the degree of lung adenocarcinoma invasion, but their sensitivity and specificity were not high. Ki-67 combined with CT imaging features could achieve a higher prediction efficiency.Conclusion Compared with Ki-67 or CT imaging features alone, the combined prediction of Ki-67 and imaging features is more effective, which is of great significance for clinicians to select the appropriate operation occasion.

Citation： ZHANG Xiaowen, ZHAO Ziwei, YE Guanzhi, FENG Yihui, ZHU Xiaolei, GENG Guojun, JIANG Jie. The efficiency of Ki-67 expression and CT imaging features in predicting the degree of lung adenocarcinoma invasion. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(10): 1277-1283. doi: 10.7507/1007-4848.202203046 Copy

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2.	Xu J, Liu P, Da J, et al. Prognostic value of Ki-67 in stage Ⅰ non-small-cell lung cancer: A meta-analysis involving 1931 patients. Pathol Res Pract, 2019, 215(5): 855-860.
3.	Walts AE, Mirocha JM, Marchevsky AM. Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas. Histopathology, 2021, 78(5): 699-709.
4.	Li Z, Li F, Pan C, et al. Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma. Lung Cancer, 2021, 154: 69-75.
5.	Yan J, Wang H, Zhou H, et al. Correlation between expression of Ki-67 and MSCT signs in different types of lung adenocarcinoma. Medicine (Baltimore), 2020, 99(2): e18678.
6.	Yoshikawa K, Shimada M, Higashijima J, et al. Ki-67 and survivin as predictive factors for rectal cancer treated with preoperative chemoradiotherapy. Anticancer Res, 2018, 38(3): 1735-1739.
7.	Chen X, He C, Han D, et al. The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: A systematic review and meta-analysis. Future Oncol, 2017, 13(9): 843-857.
8.	李媛, 谢惠康, 武春燕. WHO胸部肿瘤分类(第5版)中肺肿瘤部分解读. 中国癌症杂志, 2021, 31(7): 574-580.
9.	McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med, 2013, 369(10): 910-919.
10.	Han D, Heuvelmans MA, Vliegenthart R, et al. Influence of lung nodule margin on volume-and diameter-based reader variability in CT lung cancer screening. Br J Radiol, 2018, 91(1090): 20170405.
11.	MacMahon H, Naidich DP, Goo JM, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: From the Fleischner Society 2017. Radiology, 2017, 284(1): 228-243.
12.	Yu M, Wang Z, Yang G, et al. A model of malignant risk prediction for solitary pulmonary nodules on 18 F-FDG PET/CT: Building and estimating. Thorac Cancer, 2020, 11(5): 1211-1215.
13.	Qiu ZX, Cheng Y, Liu D, et al. Clinical, pathological, and radiological characteristics of solitary ground-glass opacity lung nodules on high-resolution computed tomography. Ther Clin Risk Manag, 2016, 12: 1445-1453.
14.	Hou H, Yu S, Xu Z, et al. Prediction of malignancy for solitary pulmonary nodules based on imaging, clinical characteristics and tumor marker levels. Eur J Cancer Prev, 2021, 30(5): 382-388.
15.	Gao F, Li M, Ge X, et al. Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels. Eur Radiol, 2013, 23(12): 3271-3277.
16.	Koenigkam Santos M, Muley T, Warth A, et al. Morphological computed tomography features of surgically resectable pulmonary squamous cell carcinomas: Impact on prognosis and comparison with adenocarcinomas. Eur J Radiol, 2014, 83(7): 1275-1281.
17.	Wilson R, Devaraj A. Radiomics of pulmonary nodules and lung cancer. Transl Lung Cancer Res, 2017, 6(1): 86-91.
18.	陈显文, 罗爱华, 曾洲红. CK5/6、P63、TTF-1和NapsinA在腺癌及鳞状细胞癌鉴别诊断中的应用. 中国医药科学, 2021, 11(10): 191-194.
19.	Ma Y, Fan M, Dai L, et al. The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma correlates with the results of surgical treatment. Tumour Biol, 2015, 36(10): 8085-8092.
20.	Schilsky JB, Ni A, Ahn L, et al. Prognostic impact of TTF-1 expression in patients with stage Ⅳ lung adenocarcinomas. Lung Cancer, 2017, 108: 205-211.
21.	Yatabe Y, Dacic S, Borczuk AC, et al. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol, 2019, 14(3): 377-407.
22.	Gerdes J, Schwab U, Lemke H, et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer, 1983, 31(1): 13-20.
23.	Bullwinkel J, Baron-Lühr B, Lüdemann A, et al. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J Cell Physiol, 2006, 206(3): 624-635.
24.	Folescu R, Levai CM, Grigoraş ML, et al. Expression and significance of Ki-67 in lung cancer. Rom J Morphol Embryol, 2018, 59(1): 227-233.
25.	Wang D, Chen D, Zhang C, et al. Analysis of the relationship between Ki-67 expression and chemotherapy and prognosis in advanced non-small cell lung cancer. Transl Cancer Res, 2020, 9(5): 3491-3498.
26.	胡利平, 邹飞, 方常练, 等. 非小细胞肺癌影像特征及病理类型联合Ki-67基因表达对术后脑转移的风险分析. 实用癌症杂志, 2019, 34(2): 219-222.
27.	Ito H, Suzuki K, Mizutani T, et al. Long-term survival outcome after lobectomy in patients with clinical T1N0 lung cancer. J Thorac Cardiovasc Surg, 2020, S0022-5223(20): 30054-4.
28.	Yamashita S, Moroga T, Tokuishi K, et al. Ki-67 labeling index is associated with recurrence after segmentectomy under video-assisted thoracoscopic surgery in stage Ⅰ non-small cell lung cancer. Ann Thorac Cardiovasc Surg, 2011, 17(4): 341-346.

1. Panunzio A, Sartori P. Lung cancer and radiological imaging. Curr Radiopharm, 2020, 13(3): 238-242.
2. Xu J, Liu P, Da J, et al. Prognostic value of Ki-67 in stage Ⅰ non-small-cell lung cancer: A meta-analysis involving 1931 patients. Pathol Res Pract, 2019, 215(5): 855-860.
3. Walts AE, Mirocha JM, Marchevsky AM. Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas. Histopathology, 2021, 78(5): 699-709.
4. Li Z, Li F, Pan C, et al. Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma. Lung Cancer, 2021, 154: 69-75.
5. Yan J, Wang H, Zhou H, et al. Correlation between expression of Ki-67 and MSCT signs in different types of lung adenocarcinoma. Medicine (Baltimore), 2020, 99(2): e18678.
6. Yoshikawa K, Shimada M, Higashijima J, et al. Ki-67 and survivin as predictive factors for rectal cancer treated with preoperative chemoradiotherapy. Anticancer Res, 2018, 38(3): 1735-1739.
7. Chen X, He C, Han D, et al. The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: A systematic review and meta-analysis. Future Oncol, 2017, 13(9): 843-857.
8. 李媛, 谢惠康, 武春燕. WHO胸部肿瘤分类(第5版)中肺肿瘤部分解读. 中国癌症杂志, 2021, 31(7): 574-580.
9. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med, 2013, 369(10): 910-919.
10. Han D, Heuvelmans MA, Vliegenthart R, et al. Influence of lung nodule margin on volume-and diameter-based reader variability in CT lung cancer screening. Br J Radiol, 2018, 91(1090): 20170405.
11. MacMahon H, Naidich DP, Goo JM, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: From the Fleischner Society 2017. Radiology, 2017, 284(1): 228-243.
12. Yu M, Wang Z, Yang G, et al. A model of malignant risk prediction for solitary pulmonary nodules on 18 F-FDG PET/CT: Building and estimating. Thorac Cancer, 2020, 11(5): 1211-1215.
13. Qiu ZX, Cheng Y, Liu D, et al. Clinical, pathological, and radiological characteristics of solitary ground-glass opacity lung nodules on high-resolution computed tomography. Ther Clin Risk Manag, 2016, 12: 1445-1453.
14. Hou H, Yu S, Xu Z, et al. Prediction of malignancy for solitary pulmonary nodules based on imaging, clinical characteristics and tumor marker levels. Eur J Cancer Prev, 2021, 30(5): 382-388.
15. Gao F, Li M, Ge X, et al. Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels. Eur Radiol, 2013, 23(12): 3271-3277.
16. Koenigkam Santos M, Muley T, Warth A, et al. Morphological computed tomography features of surgically resectable pulmonary squamous cell carcinomas: Impact on prognosis and comparison with adenocarcinomas. Eur J Radiol, 2014, 83(7): 1275-1281.
17. Wilson R, Devaraj A. Radiomics of pulmonary nodules and lung cancer. Transl Lung Cancer Res, 2017, 6(1): 86-91.
18. 陈显文, 罗爱华, 曾洲红. CK5/6、P63、TTF-1和NapsinA在腺癌及鳞状细胞癌鉴别诊断中的应用. 中国医药科学, 2021, 11(10): 191-194.
19. Ma Y, Fan M, Dai L, et al. The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma correlates with the results of surgical treatment. Tumour Biol, 2015, 36(10): 8085-8092.
20. Schilsky JB, Ni A, Ahn L, et al. Prognostic impact of TTF-1 expression in patients with stage Ⅳ lung adenocarcinomas. Lung Cancer, 2017, 108: 205-211.
21. Yatabe Y, Dacic S, Borczuk AC, et al. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol, 2019, 14(3): 377-407.
22. Gerdes J, Schwab U, Lemke H, et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer, 1983, 31(1): 13-20.
23. Bullwinkel J, Baron-Lühr B, Lüdemann A, et al. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J Cell Physiol, 2006, 206(3): 624-635.
24. Folescu R, Levai CM, Grigoraş ML, et al. Expression and significance of Ki-67 in lung cancer. Rom J Morphol Embryol, 2018, 59(1): 227-233.
25. Wang D, Chen D, Zhang C, et al. Analysis of the relationship between Ki-67 expression and chemotherapy and prognosis in advanced non-small cell lung cancer. Transl Cancer Res, 2020, 9(5): 3491-3498.
26. 胡利平, 邹飞, 方常练, 等. 非小细胞肺癌影像特征及病理类型联合Ki-67基因表达对术后脑转移的风险分析. 实用癌症杂志, 2019, 34(2): 219-222.
27. Ito H, Suzuki K, Mizutani T, et al. Long-term survival outcome after lobectomy in patients with clinical T1N0 lung cancer. J Thorac Cardiovasc Surg, 2020, S0022-5223(20): 30054-4.
28. Yamashita S, Moroga T, Tokuishi K, et al. Ki-67 labeling index is associated with recurrence after segmentectomy under video-assisted thoracoscopic surgery in stage Ⅰ non-small cell lung cancer. Ann Thorac Cardiovasc Surg, 2011, 17(4): 341-346.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The efficiency of Ki-67 expression and CT imaging features in predicting the degree of lung adenocarcinoma invasion

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