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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 Yu
Original Article – Clinical Oncology

Abstract

Purpose

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.

Methods

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

Results

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.

Conclusion

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.

Keywords

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

Abbreviations

PEAC

Primary pulmonary enteric adenocarcinoma

MCC

Pulmonary metastases from colorectal carcinoma

CRC

Colorectal cancer

NGS

Next-generation sequencing

IHC

Immunohistochemistry

FFPE

Formalin-fixed paraffin-embedded

H&E

Hematoxylin & eosin

CK7

Cytokeratin 7

TTF-1 (nkx2-1)

Thyroid transcription factor-1

CK20

Cytokeratin 20

CDX2

Caudal type homeobox 2

LOF

Loss of function

CNV

Copy number variation

NSCLC

Non-small cell lung carcinoma

LUAD

Lung adenocarcinoma

APC

Adenomatous polyposis coli protein

MMR

Mismatch repair

ALK

Anaplastic lymphoma kinase

EGFR

Epidermal growth factor receptor

KRAS

Kirsten rat sarcoma viral oncogene homolog

BRAF

Serine/threonine-protein kinase B-raf

Notes

Acknowledgements

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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