Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues.
BACKGROUND
Recepteur d'origine nantais (RON) is a receptor tyrosine kinase that is activated by a serum-derived, macrophage stimulating protein (MSP) growth factor and is expressed in many malignant tumors. The aim of the present study was to reveal the protein expression profile of RON and its relationship with clinicopathological characteristics of gastric carcinoma and prognosis.


METHODS
Gastric carcinoma tissue from 98 patients, along with 29 specimens of paraneoplastic tissue and 10 specimens of normal gastric mucosa, were examined by immunohistochemistry (IHC). Western blot analysis of 19 samples of gastric carcinoma tissue and corresponding paraneoplastic tissue, 8 specimens of normal gastric mucosa, and 2 specimens of normal lymph node samples also detected expression of a splice variant of RON, RONDelta165. All samples obtained were accompanied by patient follow-up data that ranged from 3 to 89 months (median time: 22 months).


RESULTS
The rate of positive RON expression differed significantly between gastric carcinoma tissues [56.1%, (55/98)] and paraneoplastic tissues [25.6%, (8/29)] (p = 0.007). In contrast, RON expression was absent in normal gastric mucosa samples. RON expression positively correlated with the invasive depth of the tumor (p = 0.019), perigastric lymph nodes metastasis (p = 0.019), and TNM stage (p = 0.001). However, RON expression was independent of tumor growth pattern according to Bormann criteria (p = 0.209), histopathological grade (p = 0.196), and incidence of distant metastasis (p = 0.400). RON expression was not related to a patient's survival rate (p = 0.195). RONDelta165 was strongly expressed in fresh gastric carcinoma tissue, corresponding paraneoplastic tissue, and perigastric lymph nodes with metastatic carcinoma. In contrast, expression of RONDelta165 was not observed in normal gastric mucosa and normal lymph node tissue samples.


CONCLUSIONS
RON expression is significant in gastric carcinoma tissue and corresponding paraneoplastic tissue, but is not expressed in normal gastric mucosa. Expression of RONDelta165 was similarly observed in gastric carcinoma tissue and in metastases present in lymph node tissues. We hypothesize that RON and its splice variant play an important role in the occurrence, progression, and metastasis of gastric carcinoma, and therefore may represent a useful marker to evaluate the biological activity of gastric carcinoma.
Zhou
Donghui
D
Department of oncology, The First Affiliated Hospital of College of Medicine of Zhejiang University, Hangzhou, PR China. zdh19838@hotmail.com
Pan
Gang
G
Zheng
Chen
C
Zheng
Jingjing
J
Yian
Liping
L
Teng
Xiaodong
X
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020033:Protein Isoforms / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D020033:Protein Isoforms; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases