LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.
OBJECTIVE
LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer.


METHODS
We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.


RESULTS
Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results.


CONCLUSIONS
LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer.
Nakata
Kohei
K
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Ohuchida
Kenoki
K
Nagai
Eishi
E
Hayashi
Akifumi
A
Miyasaka
Yoshihiro
Y
Kayashima
Tadashi
T
Yu
Jun
J
Aishima
Shinichi
S
Oda
Yoshinao
Y
Mizumoto
Kazuhiro
K
Tanaka
Masao
M
Tsuneyoshi
Masazumi
M
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins; D008297:Male; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins