In:
Histopathology, Wiley, Vol. 74, No. 6 ( 2019-05), p. 873-882
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0309-0167
,
1365-2559
DOI:
10.1111/his.2019.74.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2006447-0
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