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SMAD 4 alteration associates with invasive‐front pathological markers and poor prognosis in colorectal cancer
Author(s) -
Oyanagi Hidehito,
Shimada Yoshifumi,
Nagahashi Masayuki,
Ichikawa Hiroshi,
Tajima Yosuke,
Abe Kaoru,
Nakano Masato,
Kameyama Hitoshi,
Takii Yasumasa,
Kawasaki Takashi,
Homma KeiIchi,
Ling Yiwei,
Okuda Shujiro,
Takabe Kazuaki,
Wakai Toshifumi
Publication year - 2019
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.13805
Subject(s) - smad , medicine , colorectal cancer , pathological , stage (stratigraphy) , immunohistochemistry , oncology , pathology , cancer , cancer research , biology , transforming growth factor , paleontology
Aims SMAD 4 acts as a tumour suppressor, and the loss of SMAD 4 is associated with poor prognosis in colorectal cancer ( CRC ) patients. Although next‐generation sequencing ( NGS ) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD 4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD 4 alteration detected with NGS in CRC . Methods and results We retrospectively investigated 201 patients with stage I– IV CRC , by using a 415‐gene panel. To analyse the relationship between SMAD 4 alteration and other clinicopathological characteristics, we evaluated clinicopathological variables, including invasive‐front pathological markers: tumour budding, poorly differentiated cluster, and Crohn‐like lymphoid reaction. Fifty‐six patients (28%) had SMAD 4 alteration: 24 and 32 patients had SMAD 4 mutation and deletion, respectively. SMAD 4 alteration was significantly associated with T category ( P = 0.027), N category ( P = 0.037), M category ( P = 0.028), and invasive‐front pathological markers, such as poorly differentiated cluster grade 3 ( P = 0.020) and absence of Crohn‐like lymphoid reaction ( P = 0.004). Immunohistochemistry revealed that SMAD 4 alteration was significantly associated with loss of SMAD 4 ( P = 0.023). In 90 patients with stage I– III disease, SMAD 4 alteration was significantly associated with poor prognosis for relapse‐free and overall survival ( P = 0.047; P = 0.022, respectively). Conversely, in 111 patients with stage IV disease, SMAD 4 alteration was not significantly associated with overall survival. Conclusion SMAD 4 alteration is associated with invasive‐front pathological markers and poor prognosis in stage I– III CRC patients.