Summary
The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed, paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), in which no statistically significant correlations with sex, mean age, tumour stage (Dukes and pTNM) and tumour grade were noted. The frequency of aneuploidy was significantly higher in patients less than 70 years of age (p < 0.01) and in tumours localized in the left colon and rectum (p< 0.002), irrespective of their stage. The tumours in which different areas could be analysed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. Comparison of the DNA content in primary tumours and in lymph node metastases (n = 49) showed a difference in DNA-ploidy in 38% of the DNA-aneuploid tumours, but in only 6% of the DNA-diploid carcinomas (p<0.02). DNA-aneuploid carcinomas tended to show a higher rate of local recurrence and were associated with an unfavourable prognosis (p = 0.04) in those patients in which complete resection of their tumours was possible (n = 72). The significantly higher mortality of patients with DNA-aneuploid carcinomas of stage pT3, as well as those with Dukes stage A and B tumours indicates that DNA-aneuploidy may be a stage-independent additional risk factor in colorectal cancer.
Similar content being viewed by others
References
Armitage NC, Robins RA, Evans DF, Turner DR, Baldwin RW, Hardcastle JD (1985) The influence of tumour cell DNA abnormalities on survival in colorectal cancer. Br J Surg 72:828–830
Banner BF, Thomas-DeLaVega JE, Roseman DL, Coon JS (1985) Should flow cytometric DNA analysis precede definitive surgery for colon carcinoma? Ann Surg 202:740–744
Bocquillon PG, Daver A, Page M, Dalifard I, Chassevent A, Cellier P, Bertrand G, Larra F, George P, Chabrun B (1989) Flow cytometric analysis of DNA abnormalities in colorectal carcinomas. Bull Cancer Paris 76:291–300
Delattre O, Olschwang S, Law DJ, Melot T, Remvikos Y, Salmon RJ, Sastre X (1989) Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 2:353–356
Dukes CE (1932) The classification of cancer of the rectum. J Pathol Bact 35:323–332
Dukes CE, Bussey HJR (1958) The spread of rectal cancer and its effect on prognosis. Br J Cancer 12:309–320
Finan PJ, Quirke P, Dixon MF, Dyson JED, Giles GR, Bird CC (1986) Is DNA aneuploidy a good prognostic indicator in patients with advanced colorectal cancer? Br J Cancer 54:327–330
Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JMA (1987) Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariable analysis. Int J Colored Dis 2:17–21
Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA (1983) Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem 31:1333–1335
Hiddeman W, von Bassewitz DB, Kleinemeier HJ, Schulte-Brochtenbeck E, Hauss J, Lingemann B, Büchner T, Grundmann E (1986) DNA stemline heterogeneity in colorectal cancer. Cancer 58:258–263
Jass JR, Sobin LH (1989) Histological typing of intestinal tumours. 2nd ed. (International Histological Classification Of Tumours). Springer, Berlin Heidelberg New York Tokyo
Kokal W, Sheibani K, Terz J, Harada JR (1986) Tumor DNA content in the prognosis of colorectal carcinoma. JAMA 255:3123–3127
Melamed MR, Enker WE, Banner P, Janov AJ, Kessler BA, Darzynkiewicz Z (1986) Flow cytometry of colorectal carcinoma. Dis Colon Rectum 29:184–186
Newaz SN, Fang WF, Strobel HW (1983) Metabolism of the carcinogen 1,2-Dimethylhydrazine by isolated human colon microsomes and human colon tumor cells in culture. Cancer 52:794–798
Petersen SE, Lorentzen M, Bichel P (1980) A mosaic subpopulation structure of human colorectal carcinomas demonstrated by flow cytometry. In: Laerum OD, Lindmo T, Thornd E (eds) Flow cytometry IV. Universitetsforlaget, Bergen, pp 412–416
Quirke P, Dixon MF, Clayden AD, Durdey P, Dyson JED, Williams NS, Bird CC (1987) Prognostic significance of DNA aneuploidy and cell proliferation in rectal adenocarcinomas. J Pathol 151:285–291
Rognum TO, Thornd E, Lund E (1987) Survival of large bowel carcinoma patients with different DNA ploidy. Br J Cancer 56:633–636
Rübe C, Valet G, Eder M (1988) Cellular DNA content and metastasis pattern in colorectal carcinomas. Virchows Arch[A] 413:419–424
Schutte B, Reynders MMJ, Wiggers G, Arends JW, Volovics L, Bosman FT, Blijham GH (1987) Retrospective analysis of the prognostic significance of DNA content and proliferative activity in large bowel carcinoma. Cancer Res 47:213–219
Scivetti P, Danova M, Riccard A, Fiocca R, Dionigi P, Mazzini G (1989) Prognostic significance of DNA content in large bowel carcinoma: a retrospective flow cytometric study. Cancer Lett 46:213–219
Scott NA, Grade JP, Weiland LH, Pemberton JH, Beart RW, Lieber MM (1987a) Flow cytometric DNA pattern from colorectal cancers how reproducible are they? Mayo Clin Proc 62:331–337
Scott NA, Wieand HS, Moertel CG, Cha SS, Beart RW, Lieber MM (1987b) Colorectal cancer. Dukes stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern. Arch Surg 122:1375–1379 Statistisches Jahrbuch 1988 für die Bundesrepublik Deutschland (1988) Statistisches Bundesamt/Wiesbaden (ed) Kohlhammer, Stuttgart und Mainz, p 389
Steen HB, Lindmo T (1979) Flow cytometry: a high resolution instrument for everyone. Science 204:403–404
Tribukait B, Hammarberg C, Rubio C (1983) Ploidy and proliferation patterns in colorectal adenocarcinomas related to Dukes classification and histopathological differentiation. A flow-cytometric DNA study. Acta Pathol Microbiol Immunol Scand (A)91:89–95
UICC International Union against Cancer (1989) TNM-Atlas, Illustrated guide to the TNM/pTNM-classification of malignant tumours. Spiessl B, Beahrs OH, Hermanek P, Hutter RVP, Scheibe O, Sobin LH, Wagner G (eds) Springer, Berlin Heidelberg New York London Paris Tokyo
Wagner G (1984) Epidemiologie des kolorektalen Karzinoms. In: Fruhmorgen C (ed) Pravention und Fruherkennung des kolorektalen Karzinoms. Springer, Berlin Heidelberg New York Tokyo
Wiggers T, Arends JW, Schutte B, Volovics L, Bosman FT (1988) A multivariate analysis of prognostic indicators in large bowel cancer. Cancer 61:386–395
Wirsching R, Valet G, Wiebecke B (1985) Klassifikation und Prognose kolorektaler Karzinome. Beurteilung mit der Mehrparameter-Durchflußzytometrie. Fortschr Med 103:584–587
Wolley RC, Schreiber K, Kass LG, Karas M, Sherman A (1982) DNA distribution in human colon carcinomas and its relationship to clinical behavior JNCI 69:15–22
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Baretton, G., Gille, J., Oevermann, E. et al. Flow-cytometric analysis of the DNA-content in paraffin-embedded tissue from colorectal carcinomas and its prognostic significance. Virchows Archiv B Cell Pathol 60, 123–131 (1991). https://doi.org/10.1007/BF02899537
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02899537