The expression of type IV collagen alpha6 chain is related to the prognosis in patients with esophageal squamous cell carcinoma.
BACKGROUND
The destruction of the basement membrane (BM) is the first step in cancer cell invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct alpha(IV) chains: alpha1(IV) to alpha6(IV). The loss of alpha5/alpha6(IV) chains from the epithelial BM at the early stage of cancer cell invasion has been reported in several cancers. However, the expression of alpha5/alpha6(IV) chains in esophageal squamous cell carcinoma (ESCC) remains unclear.


METHODS
The expression of alpha(IV) chains in 116 resected ESCC specimens was immunohistochemically examined. The role of alpha6(IV) chain was assessed in ESCC cell lines by short interfering RNA (siRNA).


RESULTS
In intraepithelial carcinoma, the alpha5/alpha6(IV) chains were stained in a continuous linear pattern in the BM. In some cases of ESCC with the invasion beyond the lamina propria, the alpha5/alpha6(IV) chains were lost in the BM zone surrounding the cancer cell nests, but in other cases they remained. In the former, the disease-free survival and overall survival were significantly better than in those with the latter. The down-regulation of alpha6(IV) chain expression by siRNA revealed a slight increase of cancer cell invasiveness.


CONCLUSIONS
The evaluation of alpha5/alpha6(IV) chains may be a useful marker for determining tumor cell properties, as a prognostic factor, in patients with ESCC.
Baba
Yoshifumi
Y
Department of Surgical Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan.
Iyama
Ken-Ichi
K
Ikeda
Koei
K
Ishikawa
Shinji
S
Hayashi
Naoko
N
Miyanari
Nobutomo
N
Sado
Yoshikazu
Y
Ninomiya
Yoshifumi
Y
Baba
Hideo
H
D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
C478159:COL4A5 protein, human; D024141:Collagen Type IV