PTEN deletion is rare but often homogeneous in gastric cancer.
OBJECTIVE
Gastric carcinoma is the second most frequent cause of cancer-related death worldwide. As PTEN is a potential modifier of tumour response to trastuzumab, a recently approved therapy in metastatic HER2 positive gastric cancer, the existence of PTEN deletions in primary gastric cancer was investigated.


METHODS
230 primary gastric cancers were analysed in a tissue microarray format by dual labelling fluorescence in situ hybridisation for PTEN deletion. HER2 analysis was also performed. To study PTEN deletion heterogeneity, all available large tissue sections from primary cancer and corresponding metastases were analysed in seven patients.


RESULTS
Eight of 180 interpretable primary gastric cancer spots showed PTEN deletions (4.4%), including seven hemizygous and one homozygous deletion. PTEN deletion was correlated with nodal (8 of 122 cases (6.6%); p=0.041) and distant metastases (4 of 19 (21.1%); p<0.001). Large section validation showed a homogeneous distribution of PTEN deletion. HER2 positivity was seen in one PTEN deleted case.


CONCLUSIONS
Genomic PTEN deletion is a rare event in gastric adenocarcinoma but correlates with metastatic disease. The homogeneous distribution pattern indicates that this alteration occurs early in tumour development.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sormeh
S
Mina
Benjamin A
BA
Bohn
Ronald
R
Simon
Antje
A
Krohn
Matthias
M
Reeh
Dirk
D
Arnold
Carsten
C
Bokemeyer
Guido
G
Sauter
Jakob R
JR
Izbicki
Andreas
A
Marx
Phillip R
PR
Stahl
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005858:Germany; D057898:Hemizygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods
D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C494929:PTEN protein, human