Introduction
Gastric adenocarcinoma (GA) with enteroblastic differentiation (GAED) is a special type of gastric carcinoma with aggressive biological behavior, which is histologically characterized by a glycogen-rich clear cytoplasm and fetal gut-like structures. GAED shows the expression of at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP) (Murakami T et al. Gastric Cancer. 2016;19(2):498-507.)1. Despite the absence of clear cytoplasm, we often encounter GA with EMs expression (GA with EM); however, the clinicopathological characteristics of GA with EM remain unclear. Regarding this point, we reported that the status of clear cell differentiation within tumors do not affect any clinicopathological or molecular pathological differences in colorectal carcinoma with the expression of enteroblastic markers which is a colorectal counterpart of GEAD (Yamashiro Y et al. Histopathology. 2020;77(3):492-502.)2. In addition, CAED has similar clinicopathological and molecular pathological characteristics to GAED, including aggressive behavior, high rates of lymphovascular invasion and liver metastasis and high frequency of TP53 mutation2. Therefore, we speculated that the same phenomenon could also be observed in GA.
Aims & Methods
A total of 688 GA samples on tissue microarray were examined for immunohistochemical (IHC) expression of three EMs (AFP, GPC3, and SALL4), and the correlations between EM expression and clinicopathological factors were analyzed. According to the status of the clear cytoplasm of tumor cells, GA showing IHC expression of EMs was classified as either GAED or GA with EM.
Results
Histological and IHC analysis revealed 94 GAEDs (13.7%), 58 GAs with EM (8.4%), and 536 conventional GAs (CGAs). Both GAED and GA with EM showed frequent lymphovascular invasion, lymph node metastasis, and liver metastasis compared to CGA. However, venous invasion was more frequent in GAED, and vice versa in GA with EM. The five-year overall survival rates for GAED, GA with EM, and CGA were 46.6%, 47.9%, and 58.2%, respectively. GAED and GA with EM showed similar trends in overall survival rates (p = 0.78). GAED had a poorer prognosis than CGA with statistical significance (p = 0.035); however, not for GA with EM (P = 0.157). Furthermore, GA with EM-positive group (GAED and GA with EM) showed a worse overall survival rate than CGA (p = 0.018).
| GAED n=94 (13.7%)
| GA with EM n=58 (8.4%)
| p value
|
Age (years) (mean±SD)
| 72.5±10.6
| 70.2±9.9
| 0.189
|
Sex (male/female)
| 76/18
| 48/10
| 0.832
|
Tumor location (U/M/L)
| 34/21/39
| 28/17/13
| 0.056
|
Tumor size (mm) (mean±SD)
| 60.9±32.3
| 65.3±40.6
| 0.483
|
Lymphatic invasion (+) n (%)
| 57 (60.6%)
| 45 (77.6%)
| <0.05
|
Venous invasion (+) n (%)
| 63 (67.0%)
| 29 (50.0%)
| <0.05
|
| Lymph node metastasis (+) n (%) | 72 (76.6%)
| 36 (62.1%)
| 0.067
|
Liver metastasis (+) n (%)
| 39 (41.5%)
| 9 (15.5%)
| <0.01
|
Growth patterns (Solid/Non-solid)
| 29 (30.9%)/65 (69.1%)
| 8 (13.8%)/50 (86.2%)
| <0.05
|
Conclusion
Interestingly, the tumor size tended to be smaller in the EM-positive group than that for CGA group, however, clinicopathologically EM-positive group was more aggressive than CGA group such as higher rate for venous invasion and liver metastasis. These findings suggest that GAED and GA with EM can be clinically classified together as aggressive tumors but can pathologically seem to be slightly different.
References
1. Murakami T et al. Gastric Cancer. 2016;19(2):498-507.
2. Yamashiro Y et al. Histopathology. 2020;77(3):492-502.
