Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 1, pp 269–279 | Cite as

Differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal carcinoma with the assistance of next-generation sequencing and immunohistochemistry

  • Jie Zhang
  • Chan Xiang
  • Yuchen Han
  • Haohua Teng
  • Xiaojing Li
  • Jinchen Shao
  • Lei Zhu
  • Han Han-Zhang
  • Junyi Ye
  • Keke YuEmail author
Original Article – Clinical Oncology



Pulmonary enteric adenocarcinoma (PEAC), defined as tumors with an enteric component exceeding 50% and a histological morphology similar to colorectal cancer (CRC) and metastatic colorectal carcinoma (MCC), is an extremely rare primary lung adenocarcinoma, which was recently recognized by World Health Organization (WHO). Adenocarcinomas with intestinal differentiation have also been described in other anatomic sites, including paranasal sinuses, extrahepatic biliary tree, uterine and cervix, ovary. The morphologic spectrum and immunohistochemical profiles of PEAC overlap with those of colonic adenocarcinomas, the diagnosis of PEAC remains challenging. Currently, colonoscopy has to be performed to confirm the diagnosis, resulting in low compliance due to its invasiveness. Due to the rareness of PEAC, its molecular signature has not been comprehensively examined.


In this study, we investigated the molecular signatures associated with PEAC and its histological counterparts, CRC and MCC using capture-based targeted sequencing.


We revealed that 12/13 (92.31%) PEAC patients harbored mutations in well-established driver genes for non-small cell lung cancer and none of them had mutations unique to CRC. Furthermore, 13/15 (86.7%) of MCC harbored mutations that are frequently seen in CRC.


Collectively, our study showed that PEAC, exhibiting a similar mutational profile with NSCLC, showed a distinctive signature from CRC and MCC. Furthermore, we derived a classification model, intergrading both IHC markers and genetic signature, to accurately diagnose PEAC.


Primary pulmonary enteric adenocarcinoma (PEAC) Pulmonary metastases from colorectal carcinoma (MCC) Next-generation sequencing (NGS) Mutation profile 



Primary pulmonary enteric adenocarcinoma


Pulmonary metastases from colorectal carcinoma


Colorectal cancer


Next-generation sequencing




Formalin-fixed paraffin-embedded


Hematoxylin & eosin


Cytokeratin 7

TTF-1 (nkx2-1)

Thyroid transcription factor-1


Cytokeratin 20


Caudal type homeobox 2


Loss of function


Copy number variation


Non-small cell lung carcinoma


Lung adenocarcinoma


Adenomatous polyposis coli protein


Mismatch repair


Anaplastic lymphoma kinase


Epidermal growth factor receptor


Kirsten rat sarcoma viral oncogene homolog


Serine/threonine-protein kinase B-raf



This work is supported by grants from the Scientific research project of Shanghai municipal health and Family Planning Commission (201740131).

Author contributions

JZ, YH, and LZ designed research, KY, CX, HT, JL, and JS performed experiments. CX, HZ, JY and KY analyzed data; CX, HZ and KY wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors disclose no potential conflicts of interest.

Supplementary material

432_2018_2788_MOESM1_ESM.doc (96 kb)
Supplementary material 1 (DOC 95 KB)
432_2018_2788_MOESM2_ESM.jpg (104 kb)
Supplementary material 2 (JPG 103 KB)
432_2018_2788_MOESM3_ESM.doc (28 kb)
Supplementary material 3 (DOC 27 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology, Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of Pathology, The Fifth People’s Hospital of ShanghaiFudan UniversityShanghaiChina
  3. 3.Burning Rock BiotechGuangzhouChina

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