TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.
OBJECTIVE
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration.


METHODS
Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns.


RESULTS
The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions.


CONCLUSIONS
DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.
Sanlioglu
Ahter D
AD
Human Gene Therapy Unit, Akdeniz University Faculty of Medicine, Antalya, Turkey
Korcum
Aylin F
AF
Pestereli
Elif
E
Erdogan
Gulgun
G
Karaveli
Seyda
S
Savas
Burhan
B
Griffith
Thomas S
TS
Sanlioglu
Salih
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis*; D053320:Receptors, Tumor Necrosis Factor, Member 10c / Q000032:analysis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis*
D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human