Fas ligand expression in cervical adenocarcinoma: relevance to lymph node metastasis and tumor progression.
OBJECTIVE
Adenocarcinoma of the cervix carries a worse prognosis than its squamous counterpart. In particular, tumors with lymph node metastasis have a miserably poor prognosis. Fas ligand (FasL) could allow the tumor cells to evade host immune surveillance and would thus promote tumor survival and possibly metastasis formation. We decided to compare FasL expression in cervical adenocarcinoma with lymph node status to determine whether FasL plays a role in lymph node metastases.


METHODS
Using immunohistochemistry, we investigated FasL expression in sections of formalin-fixed, paraffin-embedded tissue from 24 cervical adenocarcinomas. We also studied sections of seven cases with lymph node metastases. The percentage of FasL-positive cells in each tumor was recorded. FasL expression in cervical adenocarcinoma was compared with lymph node status. Statistical analysis was performed by using the Fisher exact test and the Kaplan-Meier method.


RESULTS
FasL expression was detected in 62.5% (15 of 24) of primary lesions. Significantly higher incidence of positive FasL reactivity was demonstrated in 10 of 11 tumors with lymph-vascular space (P = 0.0188), in 10 of 10 with deep stromal invasion (P = 0.0015), and in 8 of 9 cancers with lymph node metastasis (P = 0.0481). All 9 metastatic cervical adenocarcinoma in the lymph nodes showed FasL immunoreactivity in 60.7 +/- 17.7% of the metastatic cancer cells, and 7 (78%) of these had FasL immunoreactivity in greater than 50% of the cells. The survival times of patients with FasL-expressing cervical adenocarcinomas were significantly reduced compared to patients with low FasL-expressing tumors (P = 0.0018).


CONCLUSIONS
These findings indicate that FasL plays an important role in immune evasion, and progression and metastasis of cervical adenocarcinoma.
Kase
Hiroaki
H
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi dori Niigata 951-8510, Japan.
Aoki
Yoichi
Y
Tanaka
Kenichi
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D018450:Disease Progression; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins