Prognostic significance of erythropoietin and erythropoietin receptor in gastric adenocarcinoma.
OBJECTIVE
To investigate the expression of Erythropoietin (Epo) and its receptor (EpoR) in gastric adenocarcinoma (GAC) and the correlation with angiogenesis and clinicopathological features.


METHODS
The expressions of Epo, EpoR and vascular endothelial growth factor (VEGF), as well as microvessel density were evaluated in 172 GAC biopsies by immunohistochemical staining. The correlations between these parameters and patient's clinicopathological features were analyzed statistically.


RESULTS
The proportion of Epo and EpoR alterations in GAC was higher than that in adjacent normal mucosa (P = 0.035 and 0.030). Epo high-expression was associated with EpoR high-expression, Lauren type, extensive lymph node metastasis and advanced stage of GAC (P = 0.018, 0.018, 0.004 and 0), while EpoR expression was linked with older age, World Health Organization type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.013, 0.008 and 0.001). VEGF high expression was significantly correlated with EpoR low-expression, Lauren type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.001, 0.001 and 0.007). The expression of Epo or EpoR was associated with microvessel density (P = 0.004 and 0.046). On multivariate analysis, only lymph node metastasis, abnormal Epo expression and tumor nodes metastases stage were independently associated with survival. In addition, a strong association with the immunohistochemical expression of EpoR and the angiogenic protein, VEGF, was noted.


CONCLUSIONS
Increased expression of Epo and EpoR may play a significant role in the carcinogenesis, angiogenesis and progression of GAC. Epo may be an independent prognostic factor.
Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China. gzdwanglin@126.com
Lin
L
Wang
Hai-Gang
HG
Li
Zhong-Sheng
ZS
Xia
Jian-Ming
JM
Wen
Jun
J
Lv
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D011379:Prognosis; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D017467:Receptors, Erythropoietin; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin