Invasive potency related to RCAS1 expression in uterine cervical cancer.
OBJECTIVE
RCAS1 expression is significantly associated with clinical prognosis in various human cancers, which suggests that RCAS1 may be involved in acquisition of malignant phenotypes. To investigate the relationship between RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1 expression in cervical neoplasms ranging from the precancerous state to invasive cancer.


METHODS
RCAS1 expression was studied retrospectively via immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients with intraepithelial neoplasia and resected tumor tissue from 154 patients with invasive cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables in patients with a depth of cancer cell invasion into stromal tissue of >5 mm.


RESULTS
RCAS1 expression was detected in patients with intraepithelial cancer and invasive cancer but not in patients with dysplasia. The occurrence and degree of RCAS1 expression increased with the depth of invasion. In patients with invasive cancer, RCAS1 overexpression was significantly correlated with invasion of the lymph-vascular space, lymph node metastasis in two or more sites, and tumor volume; RCAS1 expression was not associated with histologic subtype. Overall survival rates for patients with RCAS1 overexpression were significantly shorter than those for patients without RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to RCAS1 expression level. Moreover, significant associations between expression levels of RCAS1 and those of MMP-1 and laminin-5 were found.


CONCLUSIONS
RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling.
Sonoda
Kenzo
K
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. kenzo@gynob.med.kyushu-u.ac.jp
Miyamoto
Shingo
S
Hirakawa
Toshio
T
Yagi
Hiroshi
H
Yotsumoto
Fusanori
F
Nakashima
Manabu
M
Watanabe
Takeshi
T
Nakano
Hitoo
H
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002273:Carcinogens; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology; D015996:Survival Rate; D013755:Tetradecanoylphorbol Acetate; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000951:Antigens, Neoplasm; D002273:Carcinogens; C120762:EBAG9 protein, human; D013755:Tetradecanoylphorbol Acetate