J Gastric Cancer.  2015 Mar;15(1):39-45. 10.5230/jgc.2015.15.1.39.

Loss of FAT Atypical Cadherin 4 Expression Is Associated with High Pathologic T Stage in Radically Resected Gastric Cancer

• Jung HY
• Cho H
• Oh MH
• Lee JH
• Lee HJ
• Jang SH
• Lee MS

• KMID: 2372369
• DOI: http://doi.org/10.5230/jgc.2015.15.1.39

Abstract

PURPOSE
Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer.
MATERIALS AND METHODS
We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of > or =10 was considered positive for FAT4 expression.
RESULTS
Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. > or =10, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. > or =10, mean survival 62.7+/-7.3 months vs. 79.1+/-3.1 months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival.
CONCLUSIONS
Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.

Keyword

FAT4 protein; Stomach neoplasms; Surgery; Disease-free survival

MeSH Terms

Cell Adhesion
Chungcheongnam-do
Classification
Cytoplasm
Disease-Free Survival
Genes, Tumor Suppressor
Immunohistochemistry
Organ Size
Risk Factors
Stomach Neoplasms*

Figure

• 

  Fig. 1 Immunohistochemical staining of FAT4 in normal gastric mucosa and gastric adenocarcinoma (×200). FAT4 expression was well preserved in normal gastric mucosa (A), while tumors showed variable expressions of FAT4. Strong and diffused FAT4 expression was seen in intestinal-type gastric adenocarcinoma (B), while focal FAT4 expression was observed in intestinal- (C) and diffuse-type (D) gastric adenocarcinoma. A total loss of the expression of FAT4 was also observed in intestinal- (E) and diffuse-type (F) gastric adenocarcinoma.

• 

  Fig. 2 Comparison of the H-scores of FAT4 immunohistochemical staining. (A) The H-scores for FAT4 in normal gastric mucosa (mean H-score, 148.1±67.4) and gastric cancer (mean H-score, 60.0±63.1). (B) The H-scores of FAT4 according to the pathologic T stage. (C) The H-scores of FAT4 according to the American Joint Committee on Cancer (AJCC) cancer staging system. *P<0.05.

• 

  Fig. 3 Disease-free survival (DFS) and overall survival (OS) in relation to FAT4 expression in gastric cancer. (A) The loss of FAT4 expression was significantly associated with poor DFS (5-year survival rate; loss vs. no loss, 68.7% vs. 86.9%, P=0.017). (B) The FAT4-negative group was associated with poor OS, but statistical significance was borderline (5-year survival rate; loss vs. no loss, 57.6% vs. 70.9%, P=0.083). *P<0.05.

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