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

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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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

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China

    Jie Zhang, Chan Xiang, Yuchen Han, Haohua Teng, Jinchen Shao, Lei Zhu & Keke Yu

  2. Department of Pathology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

    Xiaojing Li

  3. Burning Rock Biotech, Guangzhou, 510000, China

    Han Han-Zhang & Junyi Ye

Authors
  1. Jie Zhang
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  2. Chan Xiang
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  3. Yuchen Han
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  4. Haohua Teng
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  5. Xiaojing Li
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  6. Jinchen Shao
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  7. Lei Zhu
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  8. Han Han-Zhang
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  9. Junyi Ye
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  10. Keke Yu
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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.

Corresponding author

Correspondence to Keke Yu.

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The authors disclose no potential conflicts of interest.

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Zhang, J., Xiang, C., Han, Y. et al. Differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal carcinoma with the assistance of next-generation sequencing and immunohistochemistry. J Cancer Res Clin Oncol 145, 269–279 (2019). https://doi.org/10.1007/s00432-018-2788-0

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  • DOI: https://doi.org/10.1007/s00432-018-2788-0

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