Progresses on diagnostic criteria and genetic features of synchronous multiple primary lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SONG Yang ¹ , YANG Xiaoying ^1,2 , JIA Ziqi ^1,2 , BING Zhongxing ¹ , CAO Lei ¹ , CAO Zhili ¹ , GUO Chao ¹ ,  LIANG Naixin ¹ ,  LI Shanqing ¹

1. Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, P.R.China;
2. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, P.R.China;

Corresponding author：

LIANG Naixin, Email: pumchnelson@163.com; LI Shanqing, Email: lishanqing2016@126.com

Keywords：

Synchronous multiple primary lung cancer; diagnostic criteria; molecular genetic features; review

DOI：

10.7507/1007-4848.202004014

Video：

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With the broad application of high-resolution computed tomography (CT) and high rates of early lung cancer screening, the number of patients diagnosed with synchronous multiple primary lung cancer (sMPLC) has been increasing. It becomes of great prominence to distinct sMPLC from intrapulmonary metastases in clinical practice. An increasing number of studies have developed high-throughput sequencing based genetic approaches to specify the molecular characteristics of sMPLC, which contributes to a better understanding of its tumorigenesis. The genetic profile of sMPLC also benefits its diagnosis, which mainly relies on its clinicopathological criteria. Here, we summarize the progresses on the diagnostic criteria for sMPLC, and also molecular features of sMPLC from the perspective of clonality analysis.

Citation： SONG Yang, YANG Xiaoying, JIA Ziqi, BING Zhongxing, CAO Lei, CAO Zhili, GUO Chao, LIANG Naixin, LI Shanqing. Progresses on diagnostic criteria and genetic features of synchronous multiple primary lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(3): 358-362. doi: 10.7507/1007-4848.202004014 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Cao M, Chen W. Epidemiology of lung cancer in China. Thorac Cancer, 2019, 10(1): 3-7.
3.	Cheng B, Xiong S, Li C, et al. An annual review of the remarkable advances in lung cancer clinical research in 2019. J Thorac Dis, 2020, 12(3): 1056-1069.
4.	Girard N, Ostrovnaya I, Lau C, et al. Genomic and mutational profiling to assess clonal relationships between multiple non–small cell lung cancers. Clin Cancer Res, 2009, 15(16): 5184-5190.
5.	Thakur MK, Ruterbusch JJ, Schwartz AG, et al. Risk of second lung cancer in patients with previously treated lung cancer: analysis of surveillance, epidemiology and end results (SEER) Data. J Thorac Oncol, 2018, 13(1): 46-53.
6.	Shen KR, Meyers BF, Larner JM, et al. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest, 2007, 132(3 Suppl): 290s-305s.
7.	Kozower BD, Larner JM, Detterbeck FC, et al. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5 Suppl): e369S-e399S.
8.	Warth A, Macher-Goeppinger S, Muley T, et al. Clonality of multifocal nonsmall cell lung cancer: implications for staging and therapy. Eur Respir J, 2012, 39(6): 1437-1442.
9.	Takahashi Y, Shien K, Tomida S, et al. Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis. Cancer Sci, 2018, 109(11): 3634-3642.
10.	Martini N, Melamed M. Multiple primary lung cancers. J Thorac Cardiovasc Surg, 1975, 70(4): 606-612.
11.	Antakli T, Schaefer RF, Rutherford JE, et al. Second primary lung cancer. Ann Thorac Surg, 1995, 59(4): 863-867.
12.	Colice GL, Rubins J, Unger M. Follow-up and surveillance of the lung cancer patient following curative-intent therapy. Chest, 2003, 123(1_suppl): 272S-283S.
13.	Detterbeck FC, Marom EM, Arenberg DA, et al. The IASLC lung cancer staging project: background data and proposals for the application of TNM staging rules to lung cancer presenting as multiple nodules with ground glass or lepidic features or a pneumonic type of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol, 2016, 11(5): 666-680.
14.	Huang J, Behrens C, Wistuba I, et al. Molecular analysis of synchronous and metachronous tumors of the lung: impact on management and prognosis. Ann Diagn Pathol, 2001, 5(6): 321-329.
15.	Girard N, Deshpande C, Azzoli CG, et al. Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest, 2010, 137(1): 46-52.
16.	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
17.	Shimizu S, Yatabe Y, Koshikawa T, et al. High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis. Clin Cancer Res, 2000, 6(10): 3994-3999.
18.	Greenblatt MS, Bennett WP, Hollstein M, et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 1994, 54(18): 4855-4878.
19.	Chen K, Chen W, Cai J, et al. Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers. J Thorac Cardiovasc Surg, 2018, 155(1): 371-379.
20.	Mitsudomi T, Yatabe Y, Koshikawa T, et al. Mutations of the p53 tumor suppressor gene as clonal marker for multiple primary lung cancers. J Thorac Cardiovasc Surg, 1997, 114(3): 354-360.
21.	Chung KY, Mukhopadhyay T, Kim J, et al. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res, 1993, 53(7): 1676-1683.
22.	van Rens MT, Eijken EJ, Elbers JR, et al. p53 mutation analysis for definite diagnosis of multiple primary lung carcinoma. Cancer, 2002, 94(1): 188-196.
23.	Sartori G, Cavazza A, Bertolini F, et al. A subset of lung adenocarcinomas and atypical adenomatous hyperplasia–associated foci are genotypically related: an EGFR, HER2, and K-ras mutational analysis. Am J Clin Pathol, 2008, 129(2): 202-210.
24.	Takamochi K, Oh S, Matsuoka J, et al. Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. Lung Cancer, 2012, 75(3): 313-320.
25.	Wu C, Zhao C, Yang Y, et al. High discrepancy of driver mutations in patients with NSCLC and synchronous multiple lung ground-glass nodules. J Thorac Oncol, 2015, 10(5): 778-783.
26.	Vincenten JPL, van Essen HF, Lissenberg-Witte BI, et al. Clonality analysis of pulmonary tumors by genome-wide copy number profiling. PLoS One, 2019, 14(10): e0223827.
27.	Haratake N, Toyokawa G, Takada K, et al. Programmed death-ligand 1 expression and EGFR mutations in multifocal lung cancer. Ann Thorac Surg, 2018, 105: 448-454.
28.	Mansuet-Lupo A, Barritault M, Alifano M, et al. Proposal for a combined histomolecular algorithm to distinguish multiple primary adenocarcinomas from intrapulmonary metastasis in patients with multiple lung tumors. J Thorac Oncol, 2019, 14(5): 844-856.
29.	Schneider F, Derrick V, Davison JM, et al. Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging. Mod Pathol, 2016, 29(7): 735-742.
30.	Chang JC, Alex D, Bott M, et al. Comprehensive next-generation sequencing unambiguously distinguishes separate primary lung carcinomas from intrapulmonary metastases: comparison with standard histopathologic approach. Clin Cancer Res, 2019, 25(23): 7113-7125.
31.	Xiao F, Liu D, Guo Y, et al. Survival rate and prognostic factors of surgically resected clinically synchronous multiple primary non-small cell lung cancer and further differentiation from intrapulmonary metastasis. J Thorac Dis, 2017, 9(4): 990-1001.
32.	Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage Ⅰ lung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
33.	Li R, Li X, Xue R, et al. Early metastasis detected in patients with multifocal pulmonary ground-glass opacities (GGOs). Thorax, 2018, 73(3): 290-292.
34.	Wang X, Wang M, MacLennan GT, et al. Evidence for common clonal origin of multifocal lung cancers. J Natl Cancer Inst, 2009, 101(8): 560-570.
35.	Wainscoat JS, Fey MF. Assessment of clonality in human tumors: a review. Cancer Res, 1990, 50(5): 1355-1360.
36.	Knudson AG, J r. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A, 1971, 68(4): 820-823.
37.	Mao X, Young BD, Lu YJ. The application of single nucleotide polymorphism microarrays in cancer research. Curr Genomics, 2007, 8(4): 219-228.
38.	Murphy SJ, Harris FR, Kosari F, et al. Using genomics to differentiate multiple primaries from metastatic lung cancer. J Thorac Oncol, 2019, 14(9): 1567-1582.
39.	Ma P, Fu Y, Cai MC, et al. Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer. Nat Commun, 2017, 8(1): 823.
40.	Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med, 2012, 366(10): 883-892.
41.	Kordiak J, Szemraj J, Grabska-Kobylecka I, et al. Intratumor heterogeneity and tissue distribution of KRAS mutation in non-small cell lung cancer: implications for detection of mutated KRAS oncogene in exhaled breath condensate. J Cancer Res Clin Oncol, 2019, 145(1): 241-251.
42.	Grob TJ, Hoenig T, Clauditz TS, et al. Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer. Lung Cancer, 2013, 79(3): 221-227.
43.	Bai H, Wang Z, Wang Y, et al. Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer. PLoS One, 2013, 8(2): e54170.
44.	Zhai C, Cai Y, Lou F, et al. Multiple primary malignant tumors-a clinical analysis of 15, 321 patients with malignancies at a single center in China. J Cancer, 2018, 9(16): 2795-2801.
45.	Chen C, Huang X, Peng M, et al. Multiple primary lung cancer: a rising challenge. J Thorac Dis, 2019, 11(S4): S523-S536.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Cao M, Chen W. Epidemiology of lung cancer in China. Thorac Cancer, 2019, 10(1): 3-7.
3. Cheng B, Xiong S, Li C, et al. An annual review of the remarkable advances in lung cancer clinical research in 2019. J Thorac Dis, 2020, 12(3): 1056-1069.
4. Girard N, Ostrovnaya I, Lau C, et al. Genomic and mutational profiling to assess clonal relationships between multiple non–small cell lung cancers. Clin Cancer Res, 2009, 15(16): 5184-5190.
5. Thakur MK, Ruterbusch JJ, Schwartz AG, et al. Risk of second lung cancer in patients with previously treated lung cancer: analysis of surveillance, epidemiology and end results (SEER) Data. J Thorac Oncol, 2018, 13(1): 46-53.
6. Shen KR, Meyers BF, Larner JM, et al. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest, 2007, 132(3 Suppl): 290s-305s.
7. Kozower BD, Larner JM, Detterbeck FC, et al. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5 Suppl): e369S-e399S.
8. Warth A, Macher-Goeppinger S, Muley T, et al. Clonality of multifocal nonsmall cell lung cancer: implications for staging and therapy. Eur Respir J, 2012, 39(6): 1437-1442.
9. Takahashi Y, Shien K, Tomida S, et al. Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis. Cancer Sci, 2018, 109(11): 3634-3642.
10. Martini N, Melamed M. Multiple primary lung cancers. J Thorac Cardiovasc Surg, 1975, 70(4): 606-612.
11. Antakli T, Schaefer RF, Rutherford JE, et al. Second primary lung cancer. Ann Thorac Surg, 1995, 59(4): 863-867.
12. Colice GL, Rubins J, Unger M. Follow-up and surveillance of the lung cancer patient following curative-intent therapy. Chest, 2003, 123(1_suppl): 272S-283S.
13. Detterbeck FC, Marom EM, Arenberg DA, et al. The IASLC lung cancer staging project: background data and proposals for the application of TNM staging rules to lung cancer presenting as multiple nodules with ground glass or lepidic features or a pneumonic type of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol, 2016, 11(5): 666-680.
14. Huang J, Behrens C, Wistuba I, et al. Molecular analysis of synchronous and metachronous tumors of the lung: impact on management and prognosis. Ann Diagn Pathol, 2001, 5(6): 321-329.
15. Girard N, Deshpande C, Azzoli CG, et al. Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest, 2010, 137(1): 46-52.
16. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
17. Shimizu S, Yatabe Y, Koshikawa T, et al. High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis. Clin Cancer Res, 2000, 6(10): 3994-3999.
18. Greenblatt MS, Bennett WP, Hollstein M, et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 1994, 54(18): 4855-4878.
19. Chen K, Chen W, Cai J, et al. Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers. J Thorac Cardiovasc Surg, 2018, 155(1): 371-379.
20. Mitsudomi T, Yatabe Y, Koshikawa T, et al. Mutations of the p53 tumor suppressor gene as clonal marker for multiple primary lung cancers. J Thorac Cardiovasc Surg, 1997, 114(3): 354-360.
21. Chung KY, Mukhopadhyay T, Kim J, et al. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res, 1993, 53(7): 1676-1683.
22. van Rens MT, Eijken EJ, Elbers JR, et al. p53 mutation analysis for definite diagnosis of multiple primary lung carcinoma. Cancer, 2002, 94(1): 188-196.
23. Sartori G, Cavazza A, Bertolini F, et al. A subset of lung adenocarcinomas and atypical adenomatous hyperplasia–associated foci are genotypically related: an EGFR, HER2, and K-ras mutational analysis. Am J Clin Pathol, 2008, 129(2): 202-210.
24. Takamochi K, Oh S, Matsuoka J, et al. Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. Lung Cancer, 2012, 75(3): 313-320.
25. Wu C, Zhao C, Yang Y, et al. High discrepancy of driver mutations in patients with NSCLC and synchronous multiple lung ground-glass nodules. J Thorac Oncol, 2015, 10(5): 778-783.
26. Vincenten JPL, van Essen HF, Lissenberg-Witte BI, et al. Clonality analysis of pulmonary tumors by genome-wide copy number profiling. PLoS One, 2019, 14(10): e0223827.
27. Haratake N, Toyokawa G, Takada K, et al. Programmed death-ligand 1 expression and EGFR mutations in multifocal lung cancer. Ann Thorac Surg, 2018, 105: 448-454.
28. Mansuet-Lupo A, Barritault M, Alifano M, et al. Proposal for a combined histomolecular algorithm to distinguish multiple primary adenocarcinomas from intrapulmonary metastasis in patients with multiple lung tumors. J Thorac Oncol, 2019, 14(5): 844-856.
29. Schneider F, Derrick V, Davison JM, et al. Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging. Mod Pathol, 2016, 29(7): 735-742.
30. Chang JC, Alex D, Bott M, et al. Comprehensive next-generation sequencing unambiguously distinguishes separate primary lung carcinomas from intrapulmonary metastases: comparison with standard histopathologic approach. Clin Cancer Res, 2019, 25(23): 7113-7125.
31. Xiao F, Liu D, Guo Y, et al. Survival rate and prognostic factors of surgically resected clinically synchronous multiple primary non-small cell lung cancer and further differentiation from intrapulmonary metastasis. J Thorac Dis, 2017, 9(4): 990-1001.
32. Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage Ⅰ lung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
33. Li R, Li X, Xue R, et al. Early metastasis detected in patients with multifocal pulmonary ground-glass opacities (GGOs). Thorax, 2018, 73(3): 290-292.
34. Wang X, Wang M, MacLennan GT, et al. Evidence for common clonal origin of multifocal lung cancers. J Natl Cancer Inst, 2009, 101(8): 560-570.
35. Wainscoat JS, Fey MF. Assessment of clonality in human tumors: a review. Cancer Res, 1990, 50(5): 1355-1360.
36. Knudson AG, J r. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A, 1971, 68(4): 820-823.
37. Mao X, Young BD, Lu YJ. The application of single nucleotide polymorphism microarrays in cancer research. Curr Genomics, 2007, 8(4): 219-228.
38. Murphy SJ, Harris FR, Kosari F, et al. Using genomics to differentiate multiple primaries from metastatic lung cancer. J Thorac Oncol, 2019, 14(9): 1567-1582.
39. Ma P, Fu Y, Cai MC, et al. Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer. Nat Commun, 2017, 8(1): 823.
40. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med, 2012, 366(10): 883-892.
41. Kordiak J, Szemraj J, Grabska-Kobylecka I, et al. Intratumor heterogeneity and tissue distribution of KRAS mutation in non-small cell lung cancer: implications for detection of mutated KRAS oncogene in exhaled breath condensate. J Cancer Res Clin Oncol, 2019, 145(1): 241-251.
42. Grob TJ, Hoenig T, Clauditz TS, et al. Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer. Lung Cancer, 2013, 79(3): 221-227.
43. Bai H, Wang Z, Wang Y, et al. Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer. PLoS One, 2013, 8(2): e54170.
44. Zhai C, Cai Y, Lou F, et al. Multiple primary malignant tumors-a clinical analysis of 15, 321 patients with malignancies at a single center in China. J Cancer, 2018, 9(16): 2795-2801.
45. Chen C, Huang X, Peng M, et al. Multiple primary lung cancer: a rising challenge. J Thorac Dis, 2019, 11(S4): S523-S536.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Progresses on diagnostic criteria and genetic features of synchronous multiple primary lung cancer

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