Skip to main content
Top
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Metastasis | Research

The role of adenocarcinoma subtypes and immunohistochemistry in predicting lymph node metastasis in early invasive lung adenocarcinoma

Authors: Mengchao Xue, Junjie Liu, Zhenyi Li, Ming Lu, Huiying Zhang, Wen Liu, Hui Tian

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Background

Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma.

Methods

In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA).

Results

The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P < 0.001), serum amyloid (SA) (P = 0.008); carcinoma antigen 125 (CA125) (P = 0. 042); mucus composition (P = 0.003); novel aspartic proteinase of the pepsin family A (Napsin A) (P = 0.007); and cytokeratin 5/6 (CK5/6) (P = 0.042). The area under the ROC curve (AUC) was 0.843 (95% CI: 0.779–0.908) in the training cohort and 0.838 (95% CI: 0.748–0.927) in the validation cohort. the P-value of the Hosmer–Lemeshow test was 0.0613 in the training cohort and 0.8628 in the validation cohort. the bias of the training cohort corrected C-index was 0.8444 and the bias-corrected C-index for the validation cohort was 0.8375. demonstrating that the prediction model has good discriminative power and good calibration.

Conclusions

The column line graphs created showed excellent discrimination and calibration to predict lymph node status in patients with ≤ 2 cm invasive lung adenocarcinoma. In addition, the predictive model has predictive potential before the end of surgery and can inform clinical decision making.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.PubMedCrossRef Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.PubMedCrossRef
2.
go back to reference Walter JE, Heuvelmans MA, de Jong PA, Vliegenthart R, van Ooijen PMA, Peters RB, et al. Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial. Lancet Oncol. 2016;17(7):907–16.PubMedCrossRef Walter JE, Heuvelmans MA, de Jong PA, Vliegenthart R, van Ooijen PMA, Peters RB, et al. Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial. Lancet Oncol. 2016;17(7):907–16.PubMedCrossRef
3.
go back to reference Kuroda H, Sakata S, Takahashi Y, Nakada T, Oya Y, Sugita Y, et al. Subsegmental resection preserves regional pulmonary function: a focus on thoracoscopy. Thorac Cancer. 2021;12(7):1033–40.PubMedPubMedCentralCrossRef Kuroda H, Sakata S, Takahashi Y, Nakada T, Oya Y, Sugita Y, et al. Subsegmental resection preserves regional pulmonary function: a focus on thoracoscopy. Thorac Cancer. 2021;12(7):1033–40.PubMedPubMedCentralCrossRef
4.
go back to reference Iwata H, Shirahashi K, Mizuno Y, Yamamoto H, Takemura H. Feasibility of segmental resection in non-small-cell lung cancer with ground-glass opacity. Eur J Cardiothorac Surg. 2014;46(3):375–9 (discussion 9).PubMedCrossRef Iwata H, Shirahashi K, Mizuno Y, Yamamoto H, Takemura H. Feasibility of segmental resection in non-small-cell lung cancer with ground-glass opacity. Eur J Cardiothorac Surg. 2014;46(3):375–9 (discussion 9).PubMedCrossRef
5.
go back to reference Pani E, Kennedy G, Zheng X, Ukert B, Jarrar D, Gaughan C, et al. Factors associated with nodal metastasis in 2-centimeter or less non-small cell lung cancer. J Thorac Cardiovasc Surg. 2020;159(3):1088-96.e1.PubMedCrossRef Pani E, Kennedy G, Zheng X, Ukert B, Jarrar D, Gaughan C, et al. Factors associated with nodal metastasis in 2-centimeter or less non-small cell lung cancer. J Thorac Cardiovasc Surg. 2020;159(3):1088-96.e1.PubMedCrossRef
6.
go back to reference Yu X, Li Y, Shi C, Han B. Risk factors of lymph node metastasis in patients with non-small cell lung cancer ≤ 2 cm in size: a monocentric population-based analysis. Thorac Cancer. 2018;9(1):3–9.PubMedCrossRef Yu X, Li Y, Shi C, Han B. Risk factors of lymph node metastasis in patients with non-small cell lung cancer ≤ 2 cm in size: a monocentric population-based analysis. Thorac Cancer. 2018;9(1):3–9.PubMedCrossRef
7.
go back to reference Higgins KA, Chino JP, Ready N, D’Amico TA, Berry MF, Sporn T, et al. Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy. J Thorac Oncol. 2012;7(7):1141–7.PubMedCrossRef Higgins KA, Chino JP, Ready N, D’Amico TA, Berry MF, Sporn T, et al. Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy. J Thorac Oncol. 2012;7(7):1141–7.PubMedCrossRef
8.
go back to reference Gdeedo A, Van Schil P, Corthouts B, Van Mieghem F, Van Meerbeeck J, Van Marck E. Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging. Eur Respir J. 1997;10(7):1547–51.PubMedCrossRef Gdeedo A, Van Schil P, Corthouts B, Van Mieghem F, Van Meerbeeck J, Van Marck E. Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging. Eur Respir J. 1997;10(7):1547–51.PubMedCrossRef
9.
go back to reference Gupta NC, Graeber GM, Bishop HA. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small (<1 cm), intermediate (1 to 3 cm), and large (>3 cm) lymph node lesions. Chest. 2000;117(3):773–8.PubMedCrossRef Gupta NC, Graeber GM, Bishop HA. Comparative efficacy of positron emission tomography with fluorodeoxyglucose in evaluation of small (<1 cm), intermediate (1 to 3 cm), and large (>3 cm) lymph node lesions. Chest. 2000;117(3):773–8.PubMedCrossRef
10.
go back to reference Prenzel KL, Mönig SP, Sinning JM, Baldus SE, Brochhagen HG, Schneider PM, et al. Lymph node size and metastatic infiltration in non-small cell lung cancer. Chest. 2003;123(2):463–7.PubMedCrossRef Prenzel KL, Mönig SP, Sinning JM, Baldus SE, Brochhagen HG, Schneider PM, et al. Lymph node size and metastatic infiltration in non-small cell lung cancer. Chest. 2003;123(2):463–7.PubMedCrossRef
11.
go back to reference Sioris T, Järvenpää R, Kuukasjärvi P, Helin H, Saarelainen S, Tarkka M. Comparison of computed tomography and systematic lymph node dissection in determining TNM and stage in non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23(3):403–8.PubMedCrossRef Sioris T, Järvenpää R, Kuukasjärvi P, Helin H, Saarelainen S, Tarkka M. Comparison of computed tomography and systematic lymph node dissection in determining TNM and stage in non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23(3):403–8.PubMedCrossRef
12.
go back to reference Steinert HC, Hauser M, Allemann F, Engel H, Berthold T, von Schulthess GK, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology. 1997;202(2):441–6.PubMedCrossRef Steinert HC, Hauser M, Allemann F, Engel H, Berthold T, von Schulthess GK, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology. 1997;202(2):441–6.PubMedCrossRef
13.
go back to reference Hermens FH, Van Engelenburg TC, Visser FJ, Thunnissen FB, Termeer R, Janssen JP. Diagnostic yield of transbronchial histology needle aspiration in patients with mediastinal lymph node enlargement. Respiration. 2003;70(6):631–5.PubMedCrossRef Hermens FH, Van Engelenburg TC, Visser FJ, Thunnissen FB, Termeer R, Janssen JP. Diagnostic yield of transbronchial histology needle aspiration in patients with mediastinal lymph node enlargement. Respiration. 2003;70(6):631–5.PubMedCrossRef
14.
go back to reference Annema JT, Veseliç M, Versteegh MI, Willems LN, Rabe KF. Mediastinal restaging: EUS-FNA offers a new perspective. Lung Cancer. 2003;42(3):311–8.PubMedCrossRef Annema JT, Veseliç M, Versteegh MI, Willems LN, Rabe KF. Mediastinal restaging: EUS-FNA offers a new perspective. Lung Cancer. 2003;42(3):311–8.PubMedCrossRef
15.
go back to reference FreixinetGilart J, García PG, de Castro FR, Suárez PR, Rodríguez NS, de Ugarte AV. Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma. Ann Thorac Surg. 2000;70(5):1641–3.CrossRef FreixinetGilart J, García PG, de Castro FR, Suárez PR, Rodríguez NS, de Ugarte AV. Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma. Ann Thorac Surg. 2000;70(5):1641–3.CrossRef
16.
go back to reference Boffa DJ, Kosinski AS, Paul S, Mitchell JD, Onaitis M. Lymph node evaluation by open or video-assisted approaches in 11,500 anatomic lung cancer resections. Ann Thorac Surg. 2012;94(2):347–53 (discussion 53).PubMedCrossRef Boffa DJ, Kosinski AS, Paul S, Mitchell JD, Onaitis M. Lymph node evaluation by open or video-assisted approaches in 11,500 anatomic lung cancer resections. Ann Thorac Surg. 2012;94(2):347–53 (discussion 53).PubMedCrossRef
17.
go back to reference Ohtaki Y, Yoshida J, Ishii G, Aokage K, Hishida T, Nishimura M, et al. Prognostic significance of a solid component in pulmonary adenocarcinoma. Ann Thorac Surg. 2011;91(4):1051–7.PubMedCrossRef Ohtaki Y, Yoshida J, Ishii G, Aokage K, Hishida T, Nishimura M, et al. Prognostic significance of a solid component in pulmonary adenocarcinoma. Ann Thorac Surg. 2011;91(4):1051–7.PubMedCrossRef
18.
go back to reference Nitadori J, Bograd AJ, Kadota K, Sima CS, Rizk NP, Morales EA, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst. 2013;105(16):1212–20.PubMedPubMedCentralCrossRef Nitadori J, Bograd AJ, Kadota K, Sima CS, Rizk NP, Morales EA, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst. 2013;105(16):1212–20.PubMedPubMedCentralCrossRef
19.
go back to reference Wu J, Chen J, Lv X, Yang Q, Yao S, Zhang D, et al. Clinical value of serum and exhaled breath condensate inflammatory factor IL-11 levels in non-small cell lung cancer: Clinical value of IL-11 in non-small cell lung cancer. Int J Biol Markers. 2021;36(2):64–76.PubMedCrossRef Wu J, Chen J, Lv X, Yang Q, Yao S, Zhang D, et al. Clinical value of serum and exhaled breath condensate inflammatory factor IL-11 levels in non-small cell lung cancer: Clinical value of IL-11 in non-small cell lung cancer. Int J Biol Markers. 2021;36(2):64–76.PubMedCrossRef
20.
go back to reference Chen JL, Wu JN, Lv XD, Yang QC, Chen JR, Zhang DM. The value of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and hemoglobin-to-red blood cell distribution width ratio in the progression of non-small cell lung cancer. PLoS ONE. 2020;15(8):e0237947.PubMedPubMedCentralCrossRef Chen JL, Wu JN, Lv XD, Yang QC, Chen JR, Zhang DM. The value of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and hemoglobin-to-red blood cell distribution width ratio in the progression of non-small cell lung cancer. PLoS ONE. 2020;15(8):e0237947.PubMedPubMedCentralCrossRef
21.
go back to reference Jiang C, Zhao M, Hou S, Hu X, Huang J, Wang H, et al. The indicative value of serum tumor markers for metastasis and stage of non-small cell lung cancer. Cancers (Basel). 2022;14(20):5064.PubMedCrossRef Jiang C, Zhao M, Hou S, Hu X, Huang J, Wang H, et al. The indicative value of serum tumor markers for metastasis and stage of non-small cell lung cancer. Cancers (Basel). 2022;14(20):5064.PubMedCrossRef
22.
go back to reference Moon Y, Choi SY, Park JK, Lee KY. Risk factors for occult lymph node metastasis in peripheral non-small cell lung cancer with invasive component size 3 cm or less. World J Surg. 2020;44(5):1658–65.PubMedCrossRef Moon Y, Choi SY, Park JK, Lee KY. Risk factors for occult lymph node metastasis in peripheral non-small cell lung cancer with invasive component size 3 cm or less. World J Surg. 2020;44(5):1658–65.PubMedCrossRef
23.
go back to reference Liu S, Wang R, Zhang Y, Li Y, Cheng C, Pan Y, et al. Precise diagnosis of intraoperative frozen section is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma. J Clin Oncol. 2016;34(4):307–13.PubMedCrossRef Liu S, Wang R, Zhang Y, Li Y, Cheng C, Pan Y, et al. Precise diagnosis of intraoperative frozen section is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma. J Clin Oncol. 2016;34(4):307–13.PubMedCrossRef
24.
go back to reference Su H, Xie H, Dai C, Zhao S, Xie D, She Y, et al. Procedure-specific prognostic impact of micropapillary subtype may guide resection strategy in small-sized lung adenocarcinomas: a multicenter study. Ther Adv Med Oncol. 2020;12:1758835920937893.PubMedPubMedCentralCrossRef Su H, Xie H, Dai C, Zhao S, Xie D, She Y, et al. Procedure-specific prognostic impact of micropapillary subtype may guide resection strategy in small-sized lung adenocarcinomas: a multicenter study. Ther Adv Med Oncol. 2020;12:1758835920937893.PubMedPubMedCentralCrossRef
25.
go back to reference Yeh YC, Nitadori J, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, et al. Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤ 3 cm: accuracy and interobserver agreement. Histopathology. 2015;66(7):922–38.PubMedPubMedCentralCrossRef Yeh YC, Nitadori J, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, et al. Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤ 3 cm: accuracy and interobserver agreement. Histopathology. 2015;66(7):922–38.PubMedPubMedCentralCrossRef
26.
go back to reference Koike T, Koike T, Yamato Y, Yoshiya K, Toyabe S. Predictive risk factors for mediastinal lymph node metastasis in clinical stage IA non-small-cell lung cancer patients. J Thorac Oncol. 2012;7(8):1246–51.PubMedCrossRef Koike T, Koike T, Yamato Y, Yoshiya K, Toyabe S. Predictive risk factors for mediastinal lymph node metastasis in clinical stage IA non-small-cell lung cancer patients. J Thorac Oncol. 2012;7(8):1246–51.PubMedCrossRef
27.
go back to reference Ye B, Cheng M, Li W, Ge XX, Geng JF, Feng J, et al. Predictive factors for lymph node metastasis in clinical stage IA lung adenocarcinoma. Ann Thorac Surg. 2014;98(1):217–23.PubMedCrossRef Ye B, Cheng M, Li W, Ge XX, Geng JF, Feng J, et al. Predictive factors for lymph node metastasis in clinical stage IA lung adenocarcinoma. Ann Thorac Surg. 2014;98(1):217–23.PubMedCrossRef
28.
go back to reference Kanzaki R, Higashiyama M, Fujiwara A, Tokunaga T, Maeda J, Okami J, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0–1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study. Lung Cancer. 2011;71(3):333–7.PubMedCrossRef Kanzaki R, Higashiyama M, Fujiwara A, Tokunaga T, Maeda J, Okami J, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0–1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study. Lung Cancer. 2011;71(3):333–7.PubMedCrossRef
29.
go back to reference Farjah F, Lou F, Sima C, Rusch VW, Rizk NP. A prediction model for pathologic N2 disease in lung cancer patients with a negative mediastinum by positron emission tomography. J Thorac Oncol. 2013;8(9):1170–80.PubMedCrossRef Farjah F, Lou F, Sima C, Rusch VW, Rizk NP. A prediction model for pathologic N2 disease in lung cancer patients with a negative mediastinum by positron emission tomography. J Thorac Oncol. 2013;8(9):1170–80.PubMedCrossRef
30.
go back to reference Goksel S, Ozcelik N, Telatar G, Ardic C. The role of hematological inflammatory biomarkers in the diagnosis of lung cancer and in predicting TNM stage. Cancer Invest. 2021;39(6–7):514–20.PubMedCrossRef Goksel S, Ozcelik N, Telatar G, Ardic C. The role of hematological inflammatory biomarkers in the diagnosis of lung cancer and in predicting TNM stage. Cancer Invest. 2021;39(6–7):514–20.PubMedCrossRef
31.
go back to reference Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting Tumor-Node-Metastasis stages. Oncol Lett. 2018;16(1):483–90.PubMedPubMedCentral Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting Tumor-Node-Metastasis stages. Oncol Lett. 2018;16(1):483–90.PubMedPubMedCentral
32.
go back to reference Yip R, Li K, Liu L, Xu D, Tam K, Yankelevitz DF, et al. Controversies on lung cancers manifesting as part-solid nodules. Eur Radiol. 2018;28(2):747–59.PubMedCrossRef Yip R, Li K, Liu L, Xu D, Tam K, Yankelevitz DF, et al. Controversies on lung cancers manifesting as part-solid nodules. Eur Radiol. 2018;28(2):747–59.PubMedCrossRef
33.
go back to reference Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. International association for the study of lung cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011;8(5):381–5.PubMedCrossRef Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, Yatabe Y, et al. International association for the study of lung cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011;8(5):381–5.PubMedCrossRef
34.
go back to reference Obuchowski NA, Bullen JA. Receiver operating characteristic (ROC) curves: review of methods with applications in diagnostic medicine. Phys Med Biol. 2018;63(7):07tr1.CrossRef Obuchowski NA, Bullen JA. Receiver operating characteristic (ROC) curves: review of methods with applications in diagnostic medicine. Phys Med Biol. 2018;63(7):07tr1.CrossRef
35.
go back to reference Nattino G, Pennell ML, Lemeshow S. Assessing the goodness of fit of logistic regression models in large samples: a modification of the Hosmer-Lemeshow test. Biometrics. 2020;76(2):549–60.PubMedCrossRef Nattino G, Pennell ML, Lemeshow S. Assessing the goodness of fit of logistic regression models in large samples: a modification of the Hosmer-Lemeshow test. Biometrics. 2020;76(2):549–60.PubMedCrossRef
36.
go back to reference Rosenfeld JP, Donchin E. Resampling (bootstrapping) the mean: a definite do. Psychophysiology. 2015;52(7):969–72.PubMedCrossRef Rosenfeld JP, Donchin E. Resampling (bootstrapping) the mean: a definite do. Psychophysiology. 2015;52(7):969–72.PubMedCrossRef
38.
go back to reference Huang L, Li W, Zhao L, Li B, Chai Y. Risk factors of lymph node metastasis in lung squamous cell carcinoma of 3 cm or less in diameter. Medicine (Baltimore). 2017;96(29):e7563.PubMedCrossRef Huang L, Li W, Zhao L, Li B, Chai Y. Risk factors of lymph node metastasis in lung squamous cell carcinoma of 3 cm or less in diameter. Medicine (Baltimore). 2017;96(29):e7563.PubMedCrossRef
39.
go back to reference Haruki T, Wakahara M, Matsuoka Y, Miwa K, Araki K, Taniguchi Y, et al. Clinicopathological characteristics of lung adenocarcinoma with unexpected lymph node metastasis. Ann Thorac Cardiovasc Surg. 2017;23(4):181–7.PubMedPubMedCentralCrossRef Haruki T, Wakahara M, Matsuoka Y, Miwa K, Araki K, Taniguchi Y, et al. Clinicopathological characteristics of lung adenocarcinoma with unexpected lymph node metastasis. Ann Thorac Cardiovasc Surg. 2017;23(4):181–7.PubMedPubMedCentralCrossRef
40.
go back to reference Xia W, Wang A, Jin M, Mao Q, Xia W, Dong G, et al. Young age increases risk for lymph node positivity but decreases risk for non-small cell lung cancer death. Cancer Manag Res. 2018;10:41–8.PubMedPubMedCentralCrossRef Xia W, Wang A, Jin M, Mao Q, Xia W, Dong G, et al. Young age increases risk for lymph node positivity but decreases risk for non-small cell lung cancer death. Cancer Manag Res. 2018;10:41–8.PubMedPubMedCentralCrossRef
41.
go back to reference Chen B, Wang X, Yu X, Xia WJ, Zhao H, Li XF, et al. Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study. Thorac Cancer. 2019;10(3):533–42.PubMedPubMedCentralCrossRef Chen B, Wang X, Yu X, Xia WJ, Zhao H, Li XF, et al. Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study. Thorac Cancer. 2019;10(3):533–42.PubMedPubMedCentralCrossRef
42.
go back to reference Shafazand S, Gould MK. A clinical prediction rule to estimate the probability of mediastinal metastasis in patients with non-small cell lung cancer. J Thorac Oncol. 2006;1(9):953–9.PubMedCrossRef Shafazand S, Gould MK. A clinical prediction rule to estimate the probability of mediastinal metastasis in patients with non-small cell lung cancer. J Thorac Oncol. 2006;1(9):953–9.PubMedCrossRef
43.
go back to reference Zhang Y, Sun Y, Xiang J, Zhang Y, Hu H, Chen H. A prediction model for N2 disease in T1 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;144(6):1360–4.PubMedCrossRef Zhang Y, Sun Y, Xiang J, Zhang Y, Hu H, Chen H. A prediction model for N2 disease in T1 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;144(6):1360–4.PubMedCrossRef
44.
go back to reference Zhang Y, Sun Y, Shen L, Li Y, Xiang J, Zhang Y, et al. Predictive factors of lymph node status in small peripheral non-small cell lung cancers: tumor histology is more reliable. Ann Surg Oncol. 2013;20(6):1949–54.PubMedCrossRef Zhang Y, Sun Y, Shen L, Li Y, Xiang J, Zhang Y, et al. Predictive factors of lymph node status in small peripheral non-small cell lung cancers: tumor histology is more reliable. Ann Surg Oncol. 2013;20(6):1949–54.PubMedCrossRef
45.
go back to reference Li X, Zhang H, Xing L, Xu X, Xie P, Ma H, et al. Predictive value of primary fluorine-18 fluorodeoxyglucose standard uptake value for a better choice of systematic nodal dissection or sampling in clinical stage ia non–small-cell lung cancer. Clin Lung Cancer. 2013;14(5):568–73.PubMedCrossRef Li X, Zhang H, Xing L, Xu X, Xie P, Ma H, et al. Predictive value of primary fluorine-18 fluorodeoxyglucose standard uptake value for a better choice of systematic nodal dissection or sampling in clinical stage ia non–small-cell lung cancer. Clin Lung Cancer. 2013;14(5):568–73.PubMedCrossRef
46.
go back to reference Sakao Y, Nakazono T, Sakuragi T, Natsuaki M, Itoh T. Predictive factors for survival in surgically resected clinical IA peripheral adenocarcinoma of the lung. Ann Thorac Surg. 2004;77(4):1157–61 (discussion 61-2).PubMedCrossRef Sakao Y, Nakazono T, Sakuragi T, Natsuaki M, Itoh T. Predictive factors for survival in surgically resected clinical IA peripheral adenocarcinoma of the lung. Ann Thorac Surg. 2004;77(4):1157–61 (discussion 61-2).PubMedCrossRef
47.
go back to reference Yanagitani N, Kaira K, Sunaga N, Naito Y, Koike Y, Ishihara S, et al. Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer? Int J Clin Oncol. 2007;12(3):231–3.PubMedCrossRef Yanagitani N, Kaira K, Sunaga N, Naito Y, Koike Y, Ishihara S, et al. Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer? Int J Clin Oncol. 2007;12(3):231–3.PubMedCrossRef
48.
go back to reference Minami S, Komuta K, Asai M. A case of amylase-producing lung cancer. Nihon Kokyuki Gakkai Zasshi. 2003;41(10):717–21.PubMed Minami S, Komuta K, Asai M. A case of amylase-producing lung cancer. Nihon Kokyuki Gakkai Zasshi. 2003;41(10):717–21.PubMed
49.
go back to reference Tsukawaki M, Izawa M, Yoshida M, Araki N, Hashiba Y, Nakagawa H, et al. A case of amylase-producing lung cancer. Intern Med. 1992;31(1):60–3.PubMedCrossRef Tsukawaki M, Izawa M, Yoshida M, Araki N, Hashiba Y, Nakagawa H, et al. A case of amylase-producing lung cancer. Intern Med. 1992;31(1):60–3.PubMedCrossRef
50.
go back to reference Zhu J, Xu WG, Xiao H, Zhou Y. Application of a radiomics model for preding lymph node metastasis in non-small cell lung cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2019;50(3):373–8.PubMed Zhu J, Xu WG, Xiao H, Zhou Y. Application of a radiomics model for preding lymph node metastasis in non-small cell lung cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2019;50(3):373–8.PubMed
51.
go back to reference Liang Z, Wang HF, Wu AZ, Cai JH. Clinical value of multi-tumor markers protein biochip in the diagnosis of pulmonary carcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30(11):2516–8.PubMed Liang Z, Wang HF, Wu AZ, Cai JH. Clinical value of multi-tumor markers protein biochip in the diagnosis of pulmonary carcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30(11):2516–8.PubMed
52.
go back to reference Consorti F, Lorenzotti A, Midiri G, Di Paola M. Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol. 2000;73(2):70–4.PubMedCrossRef Consorti F, Lorenzotti A, Midiri G, Di Paola M. Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol. 2000;73(2):70–4.PubMedCrossRef
53.
go back to reference Enciu M, Aşchie M, Deacu M, Poinăreanu I. Morphological characteristics of a mucinous adenocarcinoma of the prostate: differential diagnosis considerations. Rom J Morphol Embryol. 2013;54(1):191–4.PubMed Enciu M, Aşchie M, Deacu M, Poinăreanu I. Morphological characteristics of a mucinous adenocarcinoma of the prostate: differential diagnosis considerations. Rom J Morphol Embryol. 2013;54(1):191–4.PubMed
54.
go back to reference Kunisaki C, Akiyama H, Nomura M, Matsuda G, Otsuka Y, Ono HA, et al. Clinicopathologic characteristics and surgical outcomes of mucinous gastric carcinoma. Ann Surg Oncol. 2006;13(6):836–42.PubMedCrossRef Kunisaki C, Akiyama H, Nomura M, Matsuda G, Otsuka Y, Ono HA, et al. Clinicopathologic characteristics and surgical outcomes of mucinous gastric carcinoma. Ann Surg Oncol. 2006;13(6):836–42.PubMedCrossRef
55.
go back to reference Kawamura H, Kondo Y, Osawa S, Nisida Y, Okada K, Isizu H, et al. A clinicopathologic study of mucinous adenocarcinoma of the stomach. Gastric Cancer. 2001;4(2):83–6.PubMedCrossRef Kawamura H, Kondo Y, Osawa S, Nisida Y, Okada K, Isizu H, et al. A clinicopathologic study of mucinous adenocarcinoma of the stomach. Gastric Cancer. 2001;4(2):83–6.PubMedCrossRef
56.
go back to reference Beatty PL, Narayanan S, Gariépy J, Ranganathan S, Finn OJ. Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer. Cancer Prev Res (Phila). 2010;3(4):438–46.PubMedCrossRef Beatty PL, Narayanan S, Gariépy J, Ranganathan S, Finn OJ. Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer. Cancer Prev Res (Phila). 2010;3(4):438–46.PubMedCrossRef
57.
go back to reference Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.PubMedPubMedCentralCrossRef Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.PubMedPubMedCentralCrossRef
58.
go back to reference Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31(8):992–1001.PubMedCrossRef Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31(8):992–1001.PubMedCrossRef
59.
go back to reference Cadranel J, Quoix E, Baudrin L, Mourlanette P, Moro-Sibilot D, Morere JF, et al. IFCT-0401 Trial: a phase II study of gefitinib administered as first-line treatment in advanced adenocarcinoma with bronchioloalveolar carcinoma subtype. J Thorac Oncol. 2009;4(9):1126–35.PubMedCrossRef Cadranel J, Quoix E, Baudrin L, Mourlanette P, Moro-Sibilot D, Morere JF, et al. IFCT-0401 Trial: a phase II study of gefitinib administered as first-line treatment in advanced adenocarcinoma with bronchioloalveolar carcinoma subtype. J Thorac Oncol. 2009;4(9):1126–35.PubMedCrossRef
60.
go back to reference Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA. Does lung adenocarcinoma subtype predict patient survival?: a clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol. 2011;6(9):1496–504.PubMedCrossRef Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA. Does lung adenocarcinoma subtype predict patient survival?: a clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol. 2011;6(9):1496–504.PubMedCrossRef
61.
go back to reference Lee HY, Cha MJ, Lee KS, Lee HY, Kwon OJ, Choi JY, et al. Prognosis in resected invasive mucinous adenocarcinomas of the lung: related factors and comparison with resected nonmucinous adenocarcinomas. J Thorac Oncol. 2016;11(7):1064–73.PubMedCrossRef Lee HY, Cha MJ, Lee KS, Lee HY, Kwon OJ, Choi JY, et al. Prognosis in resected invasive mucinous adenocarcinomas of the lung: related factors and comparison with resected nonmucinous adenocarcinomas. J Thorac Oncol. 2016;11(7):1064–73.PubMedCrossRef
62.
go back to reference Kadota K, Yeh YC, D’Angelo SP, Moreira AL, Kuk D, Sima CS, et al. Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation. Am J Surg Pathol. 2014;38(8):1118–27.PubMedPubMedCentralCrossRef Kadota K, Yeh YC, D’Angelo SP, Moreira AL, Kuk D, Sima CS, et al. Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation. Am J Surg Pathol. 2014;38(8):1118–27.PubMedPubMedCentralCrossRef
63.
go back to reference Kakegawa S, Shimizu K, Sugano M, Miyamae Y, Kaira K, Araki T, et al. Clinicopathological features of lung adenocarcinoma with KRAS mutations. Cancer. 2011;117(18):4257–66.PubMedCrossRef Kakegawa S, Shimizu K, Sugano M, Miyamae Y, Kaira K, Araki T, et al. Clinicopathological features of lung adenocarcinoma with KRAS mutations. Cancer. 2011;117(18):4257–66.PubMedCrossRef
64.
go back to reference Pang Z, Liu H, Chen Z, Zhu L. Establishment and validation of a novel nomogram for predicting distant metastasis in patients with invasive lung adenocarcinoma. J Coll Physicians Surg Pak. 2022;32(12):1563–9.PubMedCrossRef Pang Z, Liu H, Chen Z, Zhu L. Establishment and validation of a novel nomogram for predicting distant metastasis in patients with invasive lung adenocarcinoma. J Coll Physicians Surg Pak. 2022;32(12):1563–9.PubMedCrossRef
65.
go back to reference Tatnell PJ, Powell DJ, Hill J, Smith TS, Tew DG, Kay J. Napsins: new human aspartic proteinases. Distinction between two closely related genes. FEBS Lett. 1998;441(1):43–8.PubMedCrossRef Tatnell PJ, Powell DJ, Hill J, Smith TS, Tew DG, Kay J. Napsins: new human aspartic proteinases. Distinction between two closely related genes. FEBS Lett. 1998;441(1):43–8.PubMedCrossRef
66.
go back to reference Mori K, Kon Y, Konno A, Iwanaga T. Cellular distribution of napsin (kidney-derived aspartic protease-like protein, KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice. Arch Histol Cytol. 2001;64(3):319–27.PubMedCrossRef Mori K, Kon Y, Konno A, Iwanaga T. Cellular distribution of napsin (kidney-derived aspartic protease-like protein, KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice. Arch Histol Cytol. 2001;64(3):319–27.PubMedCrossRef
67.
go back to reference Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Hum Pathol. 2010;41(1):20–5.PubMedCrossRef Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Hum Pathol. 2010;41(1):20–5.PubMedCrossRef
68.
go back to reference Ueno T, Linder S, Elmberger G. Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer. 2003;88(8):1229–33.PubMedPubMedCentralCrossRef Ueno T, Linder S, Elmberger G. Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer. 2003;88(8):1229–33.PubMedPubMedCentralCrossRef
69.
go back to reference Stoll LM, Johnson MW, Gabrielson E, Askin F, Clark DP, Li QK. The utility of napsin-A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas. Cancer Cytopathol. 2010;118(6):441–9.PubMedCrossRef Stoll LM, Johnson MW, Gabrielson E, Askin F, Clark DP, Li QK. The utility of napsin-A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas. Cancer Cytopathol. 2010;118(6):441–9.PubMedCrossRef
70.
go back to reference Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J. Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray. Arch Pathol Lab Med. 2012;136(2):163–71.PubMedCrossRef Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J. Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray. Arch Pathol Lab Med. 2012;136(2):163–71.PubMedCrossRef
71.
go back to reference Agackiran Y, Ozcan A, Akyurek N, Memis L, Findik G, Kaya S. Desmoglein-3 and Napsin A double stain, a useful immunohistochemical marker for differentiation of lung squamous cell carcinoma and adenocarcinoma from other subtypes. Appl Immunohistochem Mol Morphol. 2012;20(4):350–5.PubMedCrossRef Agackiran Y, Ozcan A, Akyurek N, Memis L, Findik G, Kaya S. Desmoglein-3 and Napsin A double stain, a useful immunohistochemical marker for differentiation of lung squamous cell carcinoma and adenocarcinoma from other subtypes. Appl Immunohistochem Mol Morphol. 2012;20(4):350–5.PubMedCrossRef
72.
go back to reference Camilo R, Capelozzi VL, Siqueira SA, Del Carlo BF. Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Hum Pathol. 2006;37(5):542–6.PubMedCrossRef Camilo R, Capelozzi VL, Siqueira SA, Del Carlo BF. Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Hum Pathol. 2006;37(5):542–6.PubMedCrossRef
73.
go back to reference Downey P, Cummins R, Moran M, Gulmann C. If it’s not CK5/6 positive, TTF-1 negative it’s not a squamous cell carcinoma of lung. APMIS. 2008;116(6):526–9.PubMedCrossRef Downey P, Cummins R, Moran M, Gulmann C. If it’s not CK5/6 positive, TTF-1 negative it’s not a squamous cell carcinoma of lung. APMIS. 2008;116(6):526–9.PubMedCrossRef
74.
go back to reference Loo PS, Thomas SC, Nicolson MC, Fyfe MN, Kerr KM. Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol. 2010;5(4):442–7.PubMedCrossRef Loo PS, Thomas SC, Nicolson MC, Fyfe MN, Kerr KM. Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol. 2010;5(4):442–7.PubMedCrossRef
Metadata
Title
The role of adenocarcinoma subtypes and immunohistochemistry in predicting lymph node metastasis in early invasive lung adenocarcinoma
Authors
Mengchao Xue
Junjie Liu
Zhenyi Li
Ming Lu
Huiying Zhang
Wen Liu
Hui Tian
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Metastasis
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11843-4

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine