Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.
BACKGROUND
Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors.


METHODS
We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes.


RESULTS
In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor-node-metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05).


CONCLUSIONS
hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.
Santini
D
D
Department of Medical Oncology, University Campus Bio-Medico, via Emilio Longoni 81, 00155 Rome, Italy. d.santini@unicampus.it
Perrone
G
G
Vincenzi
B
B
Lai
R
R
Cass
C
C
Alloni
R
R
Rabitti
C
C
Antinori
A
A
Vecchio
F
F
Morini
S
S
Magistrelli
P
P
Coppola
R
R
Mackey
J R
JR
Tonini
G
G
D000230:Adenocarcinoma / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014670:Ampulla of Vater; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D003138:Common Bile Duct Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D003657:Decision Making; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015854:Up-Regulation
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D033721:Equilibrative Nucleoside Transporter 1; D019394:Ki-67 Antigen; C438649:SLC29A1 protein, human