High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction

• Published in: British journal of cancer Vol. 101; no. 1; pp. 116 - 123
• Main Authors: Kikuchi, M, Mikami, T, Sato, T, Tokuyama, W, Araki, K, Watanabe, M, Saigenji, K, Okayasu, I
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.07.2009; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; bcl-2-Associated X Protein - biosynthesis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer Research; Cancer therapies; Cell cycle; Cell Cycle Proteins - biosynthesis; Cell death; Colorectal cancer; Dehydrogenases; DNA, Single-Stranded - metabolism; DNA-Binding Proteins - biosynthesis; Drug Resistance; Endoplasmic reticulum; Epidemiology; Gastroenterology. Liver. Pancreas. Abdomen; Glucose; Humans; Immunohistochemistry; Ki-67 Antigen - biosynthesis; Logistic Models; Medical prognosis; Medical research; Medical sciences; Medicine; Middle Aged; Minichromosome Maintenance Complex Component 3; Molecular Diagnostics; Molecular Medicine; Nuclear Proteins - biosynthesis; Oncology; Pathology; Potassium; Proteins; Rectal Neoplasms - genetics; Rectal Neoplasms - metabolism; Rectal Neoplasms - pathology; Rectal Neoplasms - therapy; Regression analysis; ROC Curve; Sensitivity and Specificity; Stem cells; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Thymidylate Synthase - biosynthesis; Tumors; Vascular endothelial growth factor; Young Adult; Japan; Bax; thymidylate synthase; Ki67; chemoradiation; rectal cancer; Rectal disease; Biological marker; Cancerology; Intestinal disease; Anorectal disease; Enzyme; Transferases; Malignant tumor; Rectum cancer; Radiotherapy; Thymidylate synthase; Chemotherapy; Treatment; Methyltransferases; Ki67 antigen; Digestive diseases; Models; Combined treatment; Locally advanced stage; Predictive factor; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605105

Background: Recently, preoperative chemoradiation therapy (CRT) for rectal cancer has been increasingly used as a neoadjuvant treatment. In the present study, the relation between histological response to CRT and immunohistochemical markers in biopsy specimens was investigated. Methods: Biopsy specimens from a total of 60 patients were collected before preoperative CRT with S-1 and irinotecan, and liniac 45 Gy. Immunohistochemical staining for Ki67, Mcm3, Bax, Bcl-2, ssDNA, Grp78, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), CD34, vascular endothelial growth factor, nestin, and L-type amino-acid transporter 1 was performed to allow comparison of the Ki67 labelling index (LI), Bax score, TS score, DPD score, microvessel density by CD34, and Grp78 score with cancer regression. Results: When the cases were divided into responders (Dworak grades 3 and 4) and non-responders (grades 1 and 2) groups, good correlations were evident with Ki67 LI, Bax, Grp78, and TS expression. On multiple logistic regression analysis, Ki67 LI, Bax, and TS scores were found to be independent factors. With their use in a logistic model, P -values could predict responder cases with a sensitivity of 82.8% and a specificity of 83.9%. Conclusion Using this system, treatment strategy for locally advanced rectal cancers can be determined before chemoradiation.