Open Access

Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma

  • Authors:
    • Fei Sun
    • Pengcheng Wang
    • Yiming Zheng
    • Weiguang Jia
    • Fuxing Liu
    • Wei Xiao
    • Jingjing Bao
    • Song Wang
    • Kaijin Lu
  • View Affiliations

  • Published online on: October 31, 2017     https://doi.org/10.3892/ol.2017.7312
  • Pages: 489-494
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Primary pulmonary mucinous adenocarcinoma (PPMA) is an uncommon subtype of lung adenocarcinoma. The present study attempted to clarify the diagnosis, clinicopathological characteristics, and pathologic significance of epithelial growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations and the prognosis of PPMA. A total of 29 patients with PPMA from among 1,469 surgically resected patients with lung adenocarcinoma were enrolled. All of the tumours expressed CK7 and 5 cases exhibited co‑expression with CK20. A total of 8 cases expressed EGFR, 14 cases expressed P53 and 2 cases expressed CEA. The majority of mucinous adenocarcinomas expressed thyroid transcription factor 1, Napsin A, Villin and Cam5.2 proteins. KRAS mutations were observed in 62% of patients and were more prevalent in the lower lung lobe and in patients with invasive mucinous adenocarcinoma. A total of 2 cases exhibited an EGFR mutation, and the co‑mutation of KRAS and EGFR was only detected in 1 case. The relapse‑free and overall survival rates at 5 years were 70.4, and 81.5%, respectively. The results may assist to identify a molecular target and supply important information for a therapeutic strategy for patients with PPMA.

References

1 

Qu Y, Che N, Zhao D, Zhang C, Su D, Zhou L, Zhang L, Wang C, Zhang H and Wei L: The clinicopathological significance of ALK rearrangements and KRAS and EGFR mutations in primary pulmonary mucinous adenocarcinoma. Tumour Biol. 36:6417–6424. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Cai D, Li H, Wang R, Li Y, Pan Y, Hu H, Zhang Y, Gong R, Pan B, Sun Y and Chen H: Comparison of clinical features, molecular alterations and prognosis in morphological subgroups of lung invasive mucinous adenocarcinoma. Onco Targets Ther. 7:2127–2132. 2014.PubMed/NCBI

3 

Sambrook-Gowar FJ: An unusual mucous cyst of the lung. Thorax. 33:796–799. 1978. View Article : Google Scholar : PubMed/NCBI

4 

Kragel PJ, Devaney KO, Meth BM, Linnoila I, Frierson HF Jr and Travis WD: Mucinous cystadenoma of the lung. A report of two cases with immunohistochemical and ultrastructural analysis. Arch Pathol Lab Med. 114:1053–1056. 1990.PubMed/NCBI

5 

Gaikwad A, Gupta A, Hare S, Gomes M, Sekhon H, Souza C, Inacio J, Lad S and Seely J: Primary adenocarcinoma of lung: A pictorial review of recent updates. Eur J Radiol. 81:4146–4155. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, et al: The 2015 world health organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 10:1243–1260. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Casali C, Rossi G, Marchioni A, Sartori G, Maselli F, Longo L, Tallarico E and Morandi U: A single institution-based retrospective study of surgically treated bronchioloalveolar adenocarcinoma of the lung: Clinicopathologic analysis, molecular features and possible pitfalls in routine practice. J Thorac Oncol. 5:830–836. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Zhang Y, Sun Y, Xiang J, Zhang Y, Hu H and Chen H: A clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer. J Thorac Cardiovasc Surg. 148:1193–1199. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Hwang DH, Sholl LM, Rojas-Rudilla V, Hall DL, Shivdasani P, Garcia EP, MacConaill LE, Vivero M, Hornick JL, Kuo FC, et al: KRAS and NKX2-1 mutations in invasive mucinous adenocarcinoma of the lung. J Thorac Oncol. 11:496–503. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Rao G, Pierobon M, Kim IK, Hsu WH, Deng J, Moon YW, Petricoin EF, Zhang YW, Wang Y and Giaccone G: Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations. Sci Rep. 7:70662017. View Article : Google Scholar : PubMed/NCBI

11 

Minamimoto R, Jamali M, Gevaert O, Echegaray S, Khuong A, Hoang CD, Shrager JB, Plevritis SK, Rubin DL, Leung AN, et al: Prediction of EGFR and KRAS mutation in non-small cell lung cancer using quantitative 18F FDG-PET/CT metrics. Oncotarget. 8:52792–52801. 2017.PubMed/NCBI

12 

Kamata T, Yoshida A, Shiraishi K, Furuta K, Kosuge T, Watanabe S, Asamura H and Tsuta K: Mucinous micropapillary pattern in lung adenocarcinomas: A unique histology with genetic correlates. Histopathology. 68:356–366. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Ichinokawa H, Ishii G, Nagai K, Kawase A, Yoshida J, Nishimura M, Hishida T, Ogasawara N, Tsuchihara K and Ochiai A: Distinct clinicopathologic characteristics of lung mucinous adenocarcinoma with KRAS mutation. Hum Pathol. 44:2636–2642. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van-Schil PE, 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. 6:244–285. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Sakuma Y, Matsukuma S, Yoshihara M, Nakamura Y, Noda K, Nakayama H, Kameda Y, Tsuchiya E and Miyagi Y: Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: Confirmation of the correlations with histologic subtypes and gene mutations. Am J Clin Pathol. 128:100–108. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Yoshizawa A, Motoi N, Riely GJ, Sima CS, Gerald WL, Kris MG, Park BJ, Rusch VW and Travis WD: Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol. 24:653–664. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Warth A, Muley T, Meister M, Stenzinger A, Thomas M, Schirmacher P, Schnabel PA, Budczies J, Hoffmann H and Weichert W: The novel histologic International association for the study of lung Cancer/American thoracic society/European respiratory society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol. 30:1438–1446. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Tsuta K, Kawago M, Inoue E, Yoshida A, Takahashi F, Sakurai H, Watanabe S, Takeuchi M, Furuta K, Asamura H and Tsuda H: The utility of the proposed IASLC/ATS/ERS lung adenocarcinoma subtypes for disease prognosis and correlation of driver gene alterations. Lung Cancer. 81:371–376. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Cadranel J, Quoix E, Baudrin L, Mourlanette P, Moro-Sibilot D, Morere JF, Souquet PJ, Soria JC, Morin F and Milleron B; IFCT-0401 Trial Group, : IFCT-0401 Trial: A phase II study of gefitinib administered as first-line treatment in advanced adenocarcinoma with bronchioloalveolar carcinoma subtype. J Thorac Oncol. 4:1126–1135. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Righi L, Vatrano S, Di-Nicolantonio F, Massa F, Rossi G, Cavazza A, Volante M, Votta A, Izzo S, Lo-Iacono M, et al: Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung. J Thorac Oncol. 11:504–515. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Geles A, Gruber-Moesenbacher U, ManzlC F, Al Effah M, Grygar E, Juettner-Smolle F and Popper HH: Pulmonary mucinous adenocarcinomas: Architectural patterns in correlation with genetic changes, prognosis and survival. Virchows Arch. 467:675–686. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Kunii R, Jiang S, Hasegawa G, Yamamoto T, Umezu H, Watanabe T, Tsuchida M, Hashimoto T, Hamakubo T, Kodama T, et al: The predominant expression of hepatocyte nuclear factor 4α (HNF4α) in thyroid transcription factor-1 (TTF-1)-negative pulmonary adenocarcinoma. Histopathology. 58:467–476. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Finberg KE, Sequist LV, Joshi VA, Muzikansky A, Miller JM, Han M, Beheshti J, Chirieac LR, Mark EJ and Iafrate AJ: Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn. 9:320–326. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Watanabe H, Saito H, Yokose T, Sakuma Y, Murakami S, Kondo T, Oshita F, Ito H, Nakayama H, Yamada K and Iwazaki M: Relation between thin-section computed tomography and clinical findings of mucinous adenocarcinoma. Ann Thorac Surg. 99:975–981. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Hata A, Katakami N, Fujita S, Kaji R, Imai Y, Takahashi Y, Nishimura T, Tomii K and Ishihara K: Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma. J Thorac Oncol. 5:1197–1200. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Shim HS, Kenudson M, Zheng Z, Liebers M, Cha YJ, Ho Q Hoang, Onozato M, Phi Le L, Heist RS and Iafrate AJ: Unique Genetic and survival characteristics of invasive mucinous adenocarcinoma of the lung. J Thorac Oncol. 10:1156–1162. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

January 2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Sun, F., Wang, P., Zheng, Y., Jia, W., Liu, F., Xiao, W. ... Lu, K. (2018). Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma. Oncology Letters, 15, 489-494. https://doi.org/10.3892/ol.2017.7312
MLA
Sun, F., Wang, P., Zheng, Y., Jia, W., Liu, F., Xiao, W., Bao, J., Wang, S., Lu, K."Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma". Oncology Letters 15.1 (2018): 489-494.
Chicago
Sun, F., Wang, P., Zheng, Y., Jia, W., Liu, F., Xiao, W., Bao, J., Wang, S., Lu, K."Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma". Oncology Letters 15, no. 1 (2018): 489-494. https://doi.org/10.3892/ol.2017.7312