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SUMMARY Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really

beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the

cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH

at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were

informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly

associated with the development of recurrence (_P_= 0.01) and indicated poor survival in patients of Dukes’ classes B and C, in which most recurrences (82%) occurred. An increased rate of

tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies.

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initial publication to switch to Creative Commons licence terms, as noted at publication _ REFERENCES * Arveux, I., Boutron, M. C., Arveux, P., Liabeuf, A., Pfitzenmeyer, P. & Faivre, J.

(1997). Colon cancer in the elderly: evidence for major improvements in health care and survival. _Br J Cancer_ 76: 963–967. Article  CAS  Google Scholar  * Cawkwell, L., Bell, S. M.,

Lewis, F. A., Dixon, M. F., Taylor, G. R. & Quirke, P. (1993). Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. _Br J Cancer_

87: 1262–1267. Article  Google Scholar  * Dib, C., Faure, S., Fizames, C., Samson, D., Drouot, N., Vignal, A., Millasseau, P., Marc, S., Hazan, J., Seboun, E., Lathrop, M., Gyapay, G.,

Morissette, J. & Weissenbach, J. (1996). A comprehensive genetic map of the human genome based on 5,264 microsatellites. _Nature_ 380: 152–154. Article  CAS  Google Scholar  * Elo, J.

P., Kvist, L., Leinonen, K., Isomaa, V., Henttu, P., Lukkarinen, O. & Vihko, P. (1995). Mutated human androgen-receptor gene detected in a prostatic-cancer patient is also activated by

estradiol. _J Clin Endocrinol Metab_ 80: 3494–3500. Article  CAS  Google Scholar  * Eppert, K., Scherer, S. W., Ozcelik, H., Pirone, R., Hoodless, P., Kim, H., Tsui, L-C, Bapat, B.,

Gallinger, S., Andrulis, I. L., Thomsen, G. H., Wrana, J. L. & Attisano, L. (1996). MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in

colorectal carcinoma. _Cell_ 86: 543–552. Article  CAS  Google Scholar  * Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A.

C., Thomas, G., Kinzler, K. W. & Vogelstein, B. (1990). Identification of a chromosome 18q gene that is altered in colorectal cancers. _Science_ 247: 49–56. Article  CAS  Google Scholar

  * Fielding, L. P., Hittinger, R., Grace, R. H. & Fry, J. S. (1992). Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for

colorectal adenocarcinoma. _Lancet_ 340: 502–506. Article  CAS  Google Scholar  * Frank, C. J., McClatchey, K. D., Devaney, K. O. & Carey, T. E. (1997). Evidence that loss of chromosome

18q is associated with tumor progression. _Cancer Res_ 57: 824–827. CAS  Google Scholar  * Hedrick, L., Cho, K. R., Fearon, E. R., Wu, T-C, Kinzler, K. W. & Vogelstein, B. (1994). The

DCC gene product in cellular differentiation and colorectal tumorigenesis. _Genes Dev_ 8: 1174–1183. Article  CAS  Google Scholar  * Iino, H., Fukayama, M., Maeda, Y., Koike, M., Mori, T.,

Takahashi, T., Kikuchi-Yanoshita, R., Miyaki, M., Mizuno, S. & Watanabe, S. (1994). Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of

heterozygosity and decreased DCC expression are correlated with the metastatic potential. _Cancer_ 73: 1324–1331. Article  CAS  Google Scholar  * Jass, J. R. & Sobin, L. H. (1989).

Histological typing of intestinal tumors. In _World Health Organization. International Classification of Tumors_, 2nd edn: Springer: Berlin Google Scholar  * Jen, J., Kim, H., Piantadosi,

S., Liu, Z-F, Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B. & Hamilton, S. R. (1994). Allelic loss of chromosome 18q and prognosis in colorectal cancer. _N Engl J Med_ 331:

213–221. Article  CAS  Google Scholar  * Jernvall, P., Mäkinen, M., Karttunen, T., Mäkelä, J. & Vihko, P. (1997). Conserved area mutations of the p53 gene are concentrated in distal

colorectal cancers. _Int J Cancer (Pred Oncol)_ 74: 97–101. Article  CAS  Google Scholar  * Kato, M., Ito, Y., Kobayashi, S. & Isono, K. (1996). Detection of DCC and Ki-ras gene

alterations in colorectal carcinoma tissue as prognostic markers for liver metastatic recurrence. _Cancer_ 77: 1729–1735. Article  CAS  Google Scholar  * Kikuchi-Yanoshita, R., Konishi, M.,

Fukunari, H., Tanaka, K. & Miyaki, M. (1992). Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial

adenomatous polyposis patients. _Cancer Res_ 52: 3801–3803. CAS  PubMed  Google Scholar  * Mäkelä, J. T., Laitinen, S. T. & Kairaluoma, M. I. (1995). Five-year follow-up after radical

surgery for colorectal cancer. _Arch Surg_ 130: 1062–1067. Article  Google Scholar  * Obrand, D. I. & Gordon, P. H. (1997). Incidence and patterns of recurrence following curative

resection for colorectal carcinoma. _Dis Colon Rectum_ 40: 15–24. Article  CAS  Google Scholar  * O’Connell, M. J., Schaid, D. J., Ganju, V., Cunningham, J., Kovach, J. S. & Thibodeau,

S. N. (1992). Current status of adjuvant chemotherapy for colorectal cancer. Can molecular markers play a role in predicting prognosis? _Cancer_ 70: 1732–1739. Article  Google Scholar  *

Ponz de Leon, M., Sant, M., Micheli, A., Sacchetti, C., Digregorio, C., Fante, R., Zanghieri, G., Melotti, G. & Gatta, G. (1992). Clinical and pathological prognostic indicators in

colorectal cancer. _Cancer_ 69: 626–635. Article  CAS  Google Scholar  * Sant, M., Capocaccia, R., Verdecchia, A., Gatta, G., Micheli, A., Mariotto, A., Hakulinen, T. & Berrino, F. The

Eurocare Working Group (1995). Comparisons of colon-cancer survival among European countries: The Eurocare Study. _Int J Cancer_ 63: 43–48. Article  CAS  Google Scholar  * Swedish Rectal

Cancer Trial (1996). Local recurrence rate in a randomised multicentre trial of preoperative radiotherapy compared with operation alone in resectable rectal carcinoma. _Eur J Surg_ 162:

397–402. * Thiagalingam, S., Lengauer, C., Leach, F. S., Schutte, M., Hahn, S. A., Overhauser, J., Willson, J. K. V., Markowich, S., Hamilton, S. R., Kern, S. E., Kinzler, K. W. &

Vogelstein, B. (1996). Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. _Nature Genet_ 13: 343–346. Article  CAS  Google Scholar  * Turnbull, R. B.,

Kyle, K., Watson, F. R. & Spratt, J. (1967). Cancer of colon: the influence of the no-touch isolation technic on survival rates. _Ann Surg_ 166: 420–427. Article  Google Scholar  *

Vernava, A. M., Longo, W. E., Virgo, K. S., Coplin, M. A., Wade, T. P. & Johnson, F. E. (1994). Current follow-up strategies after resection of colon cancer. Results of a survey of

members of the American Society of Colon and Rectal Surgeons. _Dis Colon Rectum_ 37: 573–583. Article  Google Scholar  * Wright, D. K. & Manos, M. M. (1990). Sample preparation from

paraffin-embedded tissues. In _PCR Protocols: A Guide to Methods and Applications_, Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds), pp. 153–158, Academic Press: San Diego Google Scholar 

Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Biocenter Oulu and World Health Organization Collaborating Centre for Research on Reproductive Health, University of Oulu,

Kajaanintie 52 D, Oulu, FIN-90220, Finland P Jernvall & P Vihko * Department of Pathology, University of Oulu, Kajaanintie 52 D, Oulu, FIN-90220, Finland M J Mäkinen & T J Karttunen

* Department of Surgery, University of Oulu, Kajaanintie 50, Oulu, FIN-90220, Finland J Mäkelä * Department of Biosciences, Division of Biochemistry, University of Helsinki, FIN-00014,

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original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit

http://creativecommons.org/licenses/by-nc-sa/3.0/ Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Jernvall, P., Mäkinen, M., Karttunen, T. _et al._ Loss of heterozygosity at

18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers. _Br J Cancer_ 79, 903–908 (1999). https://doi.org/10.1038/sj.bjc.6690144 Download citation *

Received: 24 February 1998 * Revised: 26 May 1998 * Accepted: 08 July 1998 * Published: 29 January 1999 * Issue Date: 01 February 1999 * DOI: https://doi.org/10.1038/sj.bjc.6690144 SHARE

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clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * chromosome 18 * colorectal cancer * loss of heterozygosity * prognosis