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Gastric‐type gene expression and phenotype in non‐terminal respiratory unit type adenocarcinoma of the lung with invasive mucinous adenocarcinoma morphology
Author(s) -
Koh Myoung Ju,
Shin Dong Hoon,
Lee SoJeong,
Hwang ChungSu,
Lee Hyun Jung,
Kim Ahrong,
Park Won Young,
Lee Jung Hee,
Choi Kyung Un,
Kim Jee Yeon,
Lee Chang Hun,
Sol Mee Young
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14077
Subject(s) - adenocarcinoma , lung , immunohistochemistry , cancer research , pathology , gene , phenotype , medicine , biology , oncology , cancer , genetics
Aims We sought to determine if non‐terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. Methods and results We reviewed whole‐section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients’ samples was measured by NanoString assay. Overexpression of genes including REG4 , TFF2 , MUCL3 , FER1L6 , B3GALT5 , ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10 , FER1L6 , HNF4a , MUC5AC , REG4 , TFF1 , TFF2 and VSIGI , was increased> 15‐fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. Conclusion Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.