Correlation between Proliferative Index by DNA Flow Cytometry and Histological Features in Stomach Cancer

Kim, Hyoung Kug; Lee, Myeong Soo; Kim, Hong Yong; Han, Se Hwan; Rhu, Seok Yong; Kim, Hong Joo; Kim, Young Doug

Abstract

PURPOSE
Stomach cancer is the most prevalent malignancy in Korea. The survival rate in advanced stage disease has stayed in less than 50%. One of the possible explanation for dismal outcome of stomach cancer is various biologic behavior of cancer cells of heterogeneous clones. Introduction of flow cytometric analysis has provided objective information of cancer cell kinetics, and it could help us in deciding the appropriate adjuvant therapy. The prospective study was undertaken to evaluate the clinical implication of DNA ploidy and each proliferative fraction by DNA flowcytometry. The other aim of the study was to evaluate which one is the most valuable index for proliferative activity of cancer cells.
MATERIALS AND METHODS
One hundred and fifty-four patients who underwent gastric resection for primary stomach cancer were included in this study. Male to female ratio was 2.1: 1, and mean age was 58.2 years (range: 26-81). Resected cancer tissues were immediately transported to the flow cytometry laboratory, and analyses for DNA content and cell cycle distribution were carried out by FACScan. The results of flow cytometric analysis were studied in correlation with clinical and histologic parameters; depth of invasion, lymph node metastasis, distant metastasis, stage, Laurens classification, histologic types and grade.
RESULTS
The frequency of aneuploid cancer was 40.3% (62 cases). The mean value of GO/Gl fraction was 75.9% and that of S-phase was 16.0%. Decrease of GO/Gl correlates with lymph node metastasis (p 0.015) and stage (p-0.046). Aneuploid cancer exhibited significant decrease of GO/Gl fraction. However, there was no significant conelation between decreased GO/Gl and depth of invasion, distant metastasis, Laurens classi- fication, differentiation of the cancer cells. Patients with metastasis to the lymph node or distant organs had increased S-phase fraction (p-0.032). High S-phase fraction also correlates with advanced stage (p-0.011) and ploidy of the oancer cells (p=0.001). When the ploidy of the tumor was analysed with clinical variables, aneuploid pattern was increased in cancer cells with intestinal type according to Laurens classificatian (p=0.042), Diploid cancer had significantly lower level of S-phase fraction than aneuploid cancer (p 0.001).
CONCLUSION
Ploidy and growth fraction of the stomach cancer reflected the extent of disease in different aspects. However, there was no single parameter which reflected the extent of disease and degree of malignant potential. Furthermore, there is a possibility that S-phase & action alone is not an accurate parameter for the proliferative activity of stomach cancer cells. In conclusion, flow cytometric analyses is a valuable study providing us more precise information about biologic properties of cancer cells. However, further evaluation with longer follow-up period is imperative because the ultimate value as an prognostic factors can be estimated in respective of clinical outcomes.