The effect of apoptotic activity, survivin, Ki-67, and P-glycoprotein expression on prognosis in pancreatic carcinoma.
OBJECTIVE
The pathogenetic mechanisms that regulate the aggressive behavior of pancreatic cancer still remain to be clarified. Alterations in the apoptotic pathway and proliferative activity of tumor cells as well as mechanisms contributing to the intrinsic drug resistance of pancreatic tumors have been investigated. Survivin is a recently described antiapoptotic protein, which, when overexpressed, is associated with worse prognosis in a majority of tumors. P-glycoprotein, a product of multidrug resistance gene-1 (MDR-1) was reported to be expressed in drug-resistant tumors. The purpose of this study was to investigate whether apoptosis, its regulation by survivin, tumor cell proliferation, and P-glycoprotein expression have a significant role on the biologic behavior of pancreatic adenocarcinoma.


METHODS
Tumors of 45 patients with pancreatic adenocarcinoma were studied for the detection of survivin, P-glycoprotein, and Ki-67 expression by immunohistochemical method and apoptotic index by TUNEL method. Immunohistochemical staining was scored and Ki-67 and apoptotic indices were expressed as percentage of stained cells.


RESULTS
Immunohistochemistry for survivin and P-glycoprotein revealed positive staining in 7 (15.4%) and 36 (79.5%) of the 45 tumors, respectively. The mean Ki-67 proliferative index was 43.75 +/- 25.30%. The mean apoptotic index evaluated with the TUNEL method was 37.12 +/- 34.55% for the whole group. We found no significant association between apoptotic index, expressions of survivin and P-glycoprotein, and clinicopathologic variables and survival.


CONCLUSIONS
Apoptotic activity, survivin, and P-glycoprotein expression failed to predict the disease extent and biologic behavior in pancreatic adenocarcinoma in our cases.
Sagol
Ozül
O
Department of Pathology, Dokuz Eylül University Hospital, Izmir, Turkey. ozgul.sagol@deu.etu.tr [corrected]
Yavuzsen
Tugba
T
Oztop
Ilhan
I
Ulukus
Cagnur
C
Ylmaz
Ugur
U
Alakavuklar
Mehmet
M
Karademir
Sedat
S
Obuz
Funda
F
Astarcoğlu
Hüseyin
H
Astarcoglu
Ibrahim
I
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D000077022:Survivin
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin