Tissue microarray constructs to predict a response to chemoradiation in rectal cancer.
OBJECTIVE
To identify, using tissue microarray (TMA), an immunohistochemical panel predictive of response to ionizing radiation (IR) in rectal cancer.


METHODS
TMA constructs were prepared from archived stage II/III rectal tumors and matching adjacent mucosa (n=38) from patients treated with pre-operative chemoradiation. Immunohistochemistry (IHC) was performed for MIB, Cyclin E, p21, p27, p53, survivin, Bcl-2, and BAX. Immunoreactivity along with clinical variables was subjected to univariate and forward stepwise logistic regression analyses.


RESULTS
Pathological complete response (pCR) was 23.9%. The number of positive lymph nodes obtained in the resected specimen was associated with pCR. Immunoreactivity for MIB (Sn 15%, Sp 65%, OR 0.33), p53 (Sn 3%, Sp 84%, OR 0.16), Bcl-2 (Sn 11%, Sp 74%, OR 0.35), and BAX (Sn 92%, Sp 80%, OR 46) was associated with pathological response (all p's<0.001). Forward stepwise logistic regression analysis demonstrated that MIB was an independent predictor of a response to chemoradiation (p=0.001).


CONCLUSIONS
A combined panel of mediators of apoptosis alone or combined with clinical factors is a feasible approach that can be applied to rectal tumor biopsies to predict a response to chemoradiation. The most sensitive factor was BAX; while MIB independently predicted a response to chemoradiation.
Huerta
Sergio
S
Department of Surgery, University of Texas Southwestern Medical Center, United States. Sergio.Huerta@UTSouthwestern.edu
Hrom
John
J
Gao
Xiaohuan
X
Saha
Debabrata
D
Anthony
Thomas
T
Reinhart
Henry
H
Kapur
Payal
P
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents