Differential diagnosis of pulmonary enteric adenocarcinoma and metastatic colorectal carcinoma with the assistance of next-generation sequencing and immunohistochemistry
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.
KeywordsPrimary 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
Hematoxylin & eosin
- TTF-1 (nkx2-1)
Thyroid transcription factor-1
Caudal type homeobox 2
Loss of function
Copy number variation
Non-small cell lung carcinoma
Adenomatous polyposis coli protein
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).
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.
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