P21 and CD166 as predictive markers of poor response and outcome after fluorouracil-based chemoradiotherapy for the patients with rectal cancer.
BACKGROUND
Pre-operative chemoradiotherapy (CRT) is the standard treatment in clinical stage T3/4 or node positive rectal cancer. However, there are no established biomarkers that can predict the pathological response and clinical outcome to CRT.


METHODS
Immunohistochemical staining was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 112 patients who received 5-FU based pre-operative CRT and surgery. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1α and ALDH1 were assessed and correlated with tumor regression grades and disease free survival.


RESULTS
Of the 112 patients (M/F 74/38, median age: 62), 20 (17.9%) patients achieved pathologic complete remission (pCR). In analyzing the associations between marker expressions and tumor regression grades, high p21 expression at the pretreatment biopsy was significantly associated with non-pCR (p = 0.022) and poor disease free survival (median DFS - low vs high p21: 75.8 vs 58.1 months, p = 0.002). In the multivariate analysis, high p21 expression level at the pre-treatment biopsy was significantly associated with poor DFS (p = 0.001, HR 6.14; 95% CI 2.03, 18.55). High CD166 expression level at the pretreatment biopsy was also associated with poor DFS (p = 0.003; HR 5.61; 95% CI 1.81, 17.35).


CONCLUSIONS
These show high p21 and CD166 expression at the pretreatment biopsy were associated with tumor regression and poor prognosis in patients treated with 5-FU based CRT. Larger, prospective and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to CRT.
Sung Hoon
SH
Sim
Mi-Hyun
MH
Kang
Yu Jung
YJ
Kim
Keun-Wook
KW
Lee
Duck-Woo
DW
Kim
Sung-Bum
SB
Kang
Keun-Yong
KY
Eom
Jae-Sung
JS
Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 beon-gil, Bundang-gu, Seongnam 463-707, Korea. hye2@snu.ac.kr.
Hye Seung
HS
Lee
Jee Hyun
JH
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020410:Activated-Leukocyte Cell Adhesion Molecule
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D005472:Fluorouracil; D020741:rho GTP-Binding Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule