Impact of loss of heterozygosity of encoding phosphate and tensin homolog on the prognosis of gastric cancer.
OBJECTIVE
Encoding phosphate and tensin homolog (PTEN) is a cancer suppressor gene and it has been assumed that gene mutation and loss of heterozygosity (LOH) occurs frequently in various types of carcinoma. However, the role of LOH of PTEN and its outcome variables in gastric cancer have not been well established. In the present study, we investigated the roles of PTEN, LOH and their outcomes.


METHODS
Fresh frozen tumor samples from 119 gastric cancer patients with a primary diagnosis of gastric carcinoma were evaluated for LOH of PTEN using an automated sequencer. Results were compared with pathological parameters. The median follow-up period was 559 days.


RESULTS
Loss of heterozygosity of PTEN was observed in 17.1% of patients (13/76) diagnosed with gastric cancer. No particular relationship was found with any clinicopathological factor. However, the prognosis of patients with LOH of PTEN was significantly poor. Multivariate analyses revealed that vascular invasion, invasion depth, LOH of PTEN, histology and lymph node metastasis were correlated with survival of the patient.


CONCLUSIONS
Even though mutation of PTEN in gastric cancer has rarely been reported, according to our findings, LOH of PTEN frequently occurs in gastric cancers and is correlated with disease-related deaths. The LOH of PTEN is an independent prognostic factor and PTEN is a candidate as a haploinsufficient tumor suppressor in gastric cancers.
Oki
Eiji
E
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan. okieiji@surg2.med.kyushu-u.ac.jp
Kakeji
Yoshihiro
Y
Baba
Hideo
H
Tokunaga
Eriko
E
Nakamura
Toshihiko
T
Ueda
Naoyuki
N
Futatsugi
Motonori
M
Yamamoto
Manabu
M
Ikebe
Masahiko
M
Maehara
Yoshihiko
Y
D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics*
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human