Genetic markers predictive of response to induction chemoradiotherapy for locally advanced rectal cancers.
OBJECTIVE
Pre-operative induction chemoradiotherapy has been used to downstage advanced rectal cancers. The variation in response rates is believed to be not only dependent on tumor size but also on the biological properties of individual tumors.


METHODS
We evaluated 17 rectal cancer patients treated with induction 5 Fluorouracil-based chemoradiotherapy and subsequent surgery. The pre-treatment biopsy specimens of these patients were analyzed with antibodies to Ki-67, p53, p21(wafl/cipl) MDM-2 and BCL-2 using an avidinbiotinylated peroxidase technique.


RESULTS
There were 5 patients with a complete response and 12 patients with a partial response. The overall expression of Ki-67 was 100%, p53-76%, p21(Wafl/cip) -64%, MDM-2-47%, and BCL-2-60%. Among the complete responders the expression was 100%, 80%, 60%, 20%, and 60%, respectively, whereas among the partial responders it was 100%, 75%, 67%, 57%,, and 16%, respectively. We found the expression of BCL2 was the only significant predictor of response to preoperative chemoradiation.


CONCLUSIONS
The immunohistochemical analysis for Ki-67, p53, p21(waf1/cip1), and MDM-2 in pretreatment biopsy specimens of rectal cancer is not useful in predicting response to induction chemoradiotherapy in rectal cancers. BCL-2 expression was highly statistically significant for complete response.
Kudrimoti
Mahesh
M
Department of Radiation Medicine, University of Kentucky Medical Center, Lexington, 40536-0293, USA. mkudr0@email.uky.edu
Lee
Eun Young
EY
Kang
Yuna
Y
Ahmed
Mansoor
M
Mohiuddin
Mohammed
M
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005819:Genetic Markers; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2