Histopathological And Molecularpathological Study On The Safe Margin Of Distal Clearance Of The Rectal Cancer

H istop athologi cal and molecul arp athological study on the safe margin of distal clearance of the rectal cancer ABSTRACT Background/purpose: What is the safe margin of distal clearance of rectal cancer surgery is still controversial. Anastomotic recurrence occurred at a high rate of 5% -~ 15% which two main causes may be responsible for. One is the distal infiltration and postpoperative remains of cancer cells. The other is the newly developing cancer from an unstable premalignant state of the distal transitional mucosa, manifesting some changes in biological molecule such as oncogenes and anti-oncogenes. Less is known about the late. The aim of this study is to explore the safe margin of distal clearance of rectal cancer with histopathologcal and molecular pathological methods. Materials and methods: The bowel was opened opposite to the tumor in 30 flesh rectal cancer specimens and one piece was taken from tumor and normal tissue of each specimen respectively. A strip of bowel wall was cut away from the inferior margin of tumor to distal clearance margin of each specimen, then was sliced transversely every 0.5cm. Each piece was separated into two parts and marked well. In one part, Sum thick, lIE stained serial sections were made for the histopathological cxamination and immunohistochemistry staining with anti-p53 monoclonal antibody ; The other was used to extract genomic DNA with proteinase K? phenol/chloroform method, Mutations of K-ras oncogene and p53 anti-oncogene were detected with PCR-SSCP and silver dyeing methods. Results: 1. In 16 of 30 cases(53.3%), distal spread was found microscopically. The spread distance was within 2cm in 14 cases(87.S%), and within 3cm in all 30 cases. The distal spread and it抯 distance was correlated to the gross morphology, histological type, the involving extent and Dukes?staging, but not to the volume of the tumor. -4- 2. The positive rate of K-ras oncogene mutation in cancer and diatal peritumoral tissue was 40.0%(12/30) and 16.7%(5/30) respectively. The positive distance of distal peritumoral mucosa was within 2cm in all cases. 3. The positive rate of p53 anti-oncogene mutation in cancer and peritumoral tissue was 63.3%(19/30) and 26.6%(8/30)respectively. The positive distance of distal peritumoral mucosa was within 2cm in 75.0%(6/8) cases and was within 3cm in all cases. 4. The positive rates of p53 protein in cancer.. peritumoral and normal tissue was 43.3%(13/30) 23.3%(7/30).. 0.0% respectively. The positive distance of distal peritumoral mucosa was within 2cm in 71.4%(5/7) cases and was within 3cm in all cases. 5. The mutaton of K-ras oncogene, p53 anti-oncogene and the expression of p53 protein in peritumour mucosa were not correlated to the clinical pathologic characters of primary cancer, the distal spread and it抯 distance. Conclusions: The pathologic spread along the distal bowel wall and the positive distance of the mutatons of K-ras oncogene.. p53 anti-oncogene and the expression of p53 protein were all within 3cm in the rectal cancer.Three centimeter distal to the tumor may be the safe margin of distal elearence in rectal cancer surgery.