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.
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%.


CONCLUSIONS
Using this system, treatment strategy for locally advanced rectal cancers can be determined before chemoradiation.
Kikuchi
M
M
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. masaomi@kitasato-u.ac.jp
Mikami
T
T
Sato
T
T
Tokuyama
W
W
Araki
K
K
Watanabe
M
M
Saigenji
K
K
Okayasu
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D016015:Logistic Models; D008875:Middle Aged; D064126:Minichromosome Maintenance Complex Component 3; D009687:Nuclear Proteins / Q000096:biosynthesis; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D012680:Sensitivity and Specificity; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
C494826:BAX protein, human; D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D019394:Ki-67 Antigen; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D051028:bcl-2-Associated X Protein; D013940:Thymidylate Synthase; D064126:Minichromosome Maintenance Complex Component 3