Prognostic Significance of DNA and Apoptotic Index in Colorectal Carcinoma

Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues. Apoptotic cell death plays an important role in the proliferation and turnover of cells in various tumors. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. Flowcytometric analysis of the cellular DNA content appears to be a useful clinical prognostic indicator in colorectal cancer. The relationship of apoptotic index(AI) and proliferative indices have being investigated. We analyzed the tumor DNA content and AI in 84 patients who underwent resection for colorectal cancer between January 1989 and December 1994 in order to evaluate the prognostic significance of apoptosis, DNA ploidy and index using in situ apoptosis detection method and flowcytometry. The mean value of AI was 32.4, and median value 21. In the cellular DNA, forty-two percent of the tumors were diploidy, fifty-eight percent aneuploidy. The mean value of DNA index(DI) was 1.38, G0/G1 72%, S phase fraction 21.7%, G2/M 6.3%, and proliferative fraction 28%. There was no significant difference between AI and tumor invasion, LN metastasis, DNA ploidy, DI.(p>0.05) There was no significance between overall survival and AI, DNA ploidy, DI. But patients who had tumors with low DNA index had a significantly longer disease free survival than high DNA index.(p<0.05) As a result, this study shows that AI is a less useful as prognostic factor and DNA index is a more important prognostic factor in patients undergoing surgery for colorectal cancer.

Expression Status and Prognostic Value of bcl-2 Protein in Breast Cancer

The bcl-2 proto-oncogene was first described as a result of the chromosomal translocation t(14:18) seen in a large number of follicular B-cell lines. Bcl-2 is so far unique a proto-oncogene in that it codes for an inner mitochondrial membrane protein. This protein regulates the programmed cell death called apoptosis. This study was designed to investigate expression of bcl-2 protein in 81 human breast cancer by using immunohistochemical staining with the monoclonal antibody of bcl-2 protein. Also this factor was compared with established clinicopathological prognostic factors and hormone receptors. The bcl-2 protein expression was positive in 38(47%) cases and was negative in 43(53%) cases. There was significant correlation between bcl-2 protein expression and histologic grade(p=0.014). Positive expression of bcl-2 protein was correlated with positive estrogen(p=0.051) and progesterone(p=0.059) receptors, but this correlation was not significant. Bcl-2 expression failed to show its prognostic role for overall(p=0.115) and disease free(p=0.214) survival. In conclusion, the bcl-2 protein is often expressed in half of breast cancer, and its expression is associated with histologic grade and hormone receptor status, but the overall and disease free survival of breast cancer patient do not appear to be influenced by bcl-2 protein expression.

Prognostic Value of nm23 Protein Expression and Tumor Angiogenesis in Breast Cancer

Mortality associated with human breast carcinoma is almost entirely due to subsequent cancer metastasis, but the molecular basis of this metastasis is not well established. The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in chromosome 17q22. This gene has been known to be involved in the metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. Tumor angiogenesis, the process leading to the formation of new vessels, plays a central role in tumor progression and distant metastasis. It is implicated in the phenomenon of dormant micrometastasis. This study was designed to determine the prognostic value of expression of the nm23 protein and tumor angiogenesis in breast cancer. Also, these two factors were compared with established clinicopathological prognostic factors and hormone receptors. 118 paraffin embedded surgical specimens of breast cancer were obtained from March, 1988 to February, 1994 and were selected for study. The expression of nm23 protein was studied by using immunohistochemical staining with anti-nm23/nuclear diphosphate kinase A. Tumor angiogenesis was quantified under light microscope by counting of the tumor microvessels(MVC) which were highlighted with anti-CD31 antibodies. The patient were allocated into two groups by mean number of MVC, one group was less 42 and the other was over 42. All the patients were female. The nm23 protein expression was positive in 74(63%) cases and was negative in 44(37%) cases. There was a significant correlation between nm23 protein expression and histologic grade(p=0.023). Positive expression of nm23 protein was correlated with positive estrogen(p=0.031) and progesterone receptors(p=0.001). Also Positive expression of nm23 protein was correlated with longer disease free survival(p=0.0026) and overall survival(p=0.0048). The group of MVC42. But the MVC and established clinicopathological prognostic factors did not show any correlation, neither with hormone status. When the nm23 protein and angiogenesis were considered together, 50 cases of negative nm23 protein and MVC<42 showed the best survival in overall(p=0.0111) and disease free survival(p=0.0114) among the four groups of each combination. In conclusion, the expression of nm23 protein and tumor angiogenesis can be used as new prognostic factors in conjunction with established other prognostic factors.

Incidence of Bone metastasis and Necessity of Preoperative Bone Scanning in Breast Cancer Patient

The bone scanning has been routinely used for initial report in 1970s showed a high incidence of positive-up to 45%-results in preoperative assessment of these patients. But recent reports have questioned the routine use of bone scanning in preoperative basis by the result of much lower positive result as rate less than 1%. On this point, we analyzed 224 cases of breast cancer, which were operatively managed in the period from January 1990 to January 1995 at the department of surgery, Korea university medical center. All the cases were performed bone scanning preoperatively and followed up more than 3 months. The analytic evaluation was done about age, stage of disease, serum alkaline phosphatase level according to menopausal status and its correlation to the result of bone scanning. The result was 14 positive cases(6.3%) from bone scanning in 224 breast cancer cases, but only 8 cases(3.6%) were true positive with bone metastasis. While 35 stage I cases and 69 stage IIa ones had no true positive, 1 among 63 stage IIb cases(1.6%), 5 among 46 stage IIIa cases(10.9%) and 2 among 11 of stage IIIb ones(18.2%) had true positive. There were high bone metastasis rate in premenopausal patients(5/108 cases, 4.6%) than postmenopausal patients(3/116, 2.6%) (p0.05). All true positive patients' alkaline phosphatase level shows within normal limits. According to this result, we think that preoperative bone scanning is unnecessary as a routine procedure in Stage I and IIa breast cancer patients. Stage IIb needs more and further study for confirming the indication of bone scanning as combinations with other predictive indicator or symptoms. About Stage III disease, we conclude the bone scanning is absolutely helpful.

Nonoperative Versus Operative Treatment of Obstructive Jaundice in Unresectable Pancreatic Cancer

Despite advances in diagnostic technology, pancreatic carcinoma is usually unresectable at the time of operation. The most common problem facing the surgeon today is determining the best method of palliation for biliary obstruction. The objectives of this study were to identify the role of nonoperative treatment for obstructive jaundice in pancreatic cancer and to compare the recurrence and survival period of operative and nonoperative treatment group. During the period of September 1987 to February 1995, a operative or nonoperative treatment was performed in 65 patients with obstructive jaundice in pancreatic carcinoma, at the Department of Surgery, Korea University, College of Medicine. We classified the patients into pancreatic resection(n=12), operative bypass(n=22), and nonoperative biliary bypass(n=31) groups according to the procedure performed. And we separated the nonoperative biliary bypass into endoscopic(n=10) and percutaneous drainage(n=21) groups. There were no significant differences with respect to the mortality within the 1st month and admission period. The type of procedure had influence on the survival of 78.3%, 57.1%, and 48.1% for resection, operative bypass and nonoperative biliary bypass, respectively. During follow-up, the difference was found with respect to the recurrence of jaundice and the morbidity within the 1st month. In conclusion, in patients with unresectable pancreatic cancer, surgical bypass procedure would be more efficient for relief of biliary obstruction than nonoperative biliary drainage. Nonoperative biliary drainage for obstructive jaundice of pancreatic cancer should be used only when the patient was not a candidate for operation.