Economic and Practical Factors in Diagnosing HNPCC Using Clinical Criteria, Immunohistochemistry and Microsatellite Instability Analysis

Hereditary Cancer in Clinical Practice

Diana Eccles⁴  Karen Nugent³  Denzil May⁵  Philippa Duncan⁴  Claire Curtis⁴  Esta Wilkins⁴  Paul Strike²  David Bunyan⁴  Adrian Bateman⁵  Francesca Pigatto¹ 

[1] Division of Chemoprevention, European Institute of Oncology, via Ripamonti, Milan, Italy;Medical Statistics RDSU, Salisbury District Hospital, Salisbury, Wiltshire SP2J 8B, UK;Department of Surgery, Southampton University Hospitals NHS Trust, Southampton SO16 6YD, UK;Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2J 8B, UK;Department of Cellular Pathology, Southampton University Hospitals NHS Trust, Southampton SO16 6YD, UK

关键词: cost analysis;    microsatellite instability;    immunohistochemistry;    clinical criteria;    mutation analysis;    HNPCC;   

Others  :  812416
DOI  :  10.1186/1897-4287-2-4-175

 received in 2004-08-13, accepted in 2004-11-05,  发布年份 2004

【 摘 要 】

Aim

To determine a cost-efficient strategy for HNPCC molecular diagnostic testing.

Methods

138 families referred to a Regional Genetics Service had hMLH1 and hMSH2 mutation analysis. The sensitivity and specificity of clinical selection criteria with or without immunohistochemistry (IHC) and microsatellite instability (MSI) analysis to further refine case selection and the effect of these approaches on the cost of mutation analysis were examined.

Results

Clearly deleterious mutations were identified in 49/138 (35.5%) of all families tested. The most sensitive criteria for identifying families with MMR mutations were the full Bethesda guidelines but these have poor specificity. IHC and MSI were useful pre-screening tools.

Conclusion

A cost-efficient approach in laboratories where IHC and/or MSI analysis are available, is to use inclusive (non-specific) criteria to select cases, followed by IHC and then MSI. Where one or both results are abnormal, proceed to further mutation analysis. Where MSI or IHC or tumour blocks are not available, more restrictive clinical criteria may be more appropriate for cost-efficient case selection.

   

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, Mecklin JP, de la Chapelle A: Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998, 338:1481-1487.
• [2]Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomaki P, de la Chapelle A, Hamilton SR, Vogelstein B, Kinzler KW: Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 1996, 2:169-174.
• [3]Nystrom-Lahti M, Wu Y, Moisio AL, Hofstra RM, Osinga J, Mecklin JP, Jarvinen HJ, Leisti J, Buys CH, de la Chapelle A, Peltomaki P: DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. Hum Mol Genet 1996, 5:763-769.
• [4]Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP: Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000, 118:829-834.
• [5]Percesepe A, Anti M, Marra G, Roncucci L, Pahor M, Coco C, Armelao F, Gasbarrini G, Ponz de Leon M: Role of clinical criteria in the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC): results of a multivariate analysis. Int J Cancer 1994, 58:799-802.
• [6]Vasen HF, Mecklin JP, Khan PM, Lynch HT: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991, 34:424-425.
• [7]Marra G, Boland CR: Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst 1995, 87:1114-1125.
• [8]Bellacosa A, Genuardi M, Anti M, Viel A, Ponz DL: Hereditary nonpolyposis colorectal cancer: review of clinical, molecular genetics, and counseling aspects. Am J Med Genet 1996, 62:353-364.
• [9]Rodriguez-Bigas MA, Boland CR, Hamilton SR, Henson DE, Jass JR, Khan PM, Lynch H, Perucho M, Smyrk T, Sobin L, Srivastava S: A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997, 89:1758-1762.
• [10]Vasen HF, Watson P, Mecklin JP, Lynch HT: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999, 116:1453-1456.
• [11]Umar A, Boland CR, Terdiman JP, Syngal S, de la CA, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S: Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004, 96:261-268.
• [12]Aaltonen LA, Peltomaki P, Mecklin JP, Jarvinen H, Jass JR, Green JS, Lynch HT, Watson P, Tallqvist G, Juhola M, Sistonen P, Hamilton S, Kinzler KW, Vogelstein B, de la Chapelle A: Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 1994, 54:1645-1648.
• [13]Bocker T, Diermann J, Friedl W, Gebert J, Holinski-Feder E, Karner-Hanusch J, von Knebel-Doeberitz M, Koelble K, Moeslein G, Schackert HK, Wirtz HC, Fishel R, Ruschoff J: Microsatellite instability analysis: a multicenter study for reliability and quality control. Cancer Res 1997, 57:4739-4743.
• [14]Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN: The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet 2001, 69:780-790.
• [15]Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S: A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998, 58:5248-5257.
• [16]Samowitz WS, Slattery ML, Potter JD, Leppert MF: BAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphisms. Am J Pathol 1999, 154:1637-1641.
• [17]Hoang JM, Cottu PH, Thuille B, Salmon RJ, Thomas G, Hamelin R: BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res 1997, 57:300-303.
• [18]Loukola A, Eklin K, Laiho P, Salovaara R, Kristo P, Jarvinen H, Mecklin JP, Launonen V, Aaltonen LA: Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res 2001, 61:4545-4549.
• [19]Marcus VA, Madlensky L, Gryfe R, Kim H, So K, Millar A, Temple LK, Hsieh E, Hiruki T, Narod S, Bapat BV, Gallinger S, Redston M: Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 1999, 23:1248-1255.
• [20]Stone JG, Robertson D, Houlston RS: Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer. J Clin Pathol 2001, 54:484-487.
• [21]Holinski-Feder E, Muller-Koch Y, Friedl W, Moeslein G, Keller G, Plaschke J, Ballhausen W, Gross M, Baldwin-Jedele K, Jungck M, Mangold E, Vogelsang H, Schackert HK, Lohsea P, Murken J, Meitinger T: DHPLC mutation analysis of the hereditary nonpolyposis colon cancer (HNPCC) genes hMLH1 and hMSH2. J Biochem Biophys Methods 2001, 47:21-32.
• [22]Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE: Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet 2000, 37:641-645.
• [23]Muller W, Burgart LJ, Krause-Paulus R, Thibodeau SN, Almeida M, Edmonston TB, Boland CR, Sutter C, Jass JR, Lindblom A, Lubinski J, MacDermot K, Sanders DS, Morreau H, Muller A, Oliani C, Orntoft T, Ponz De Leon M, Rosty C, Rodriguez-Bigas M, Ruschoff J, Ruszkiewicz A, Sabourin J, Salovaara R, Moslein G, ICG-HNPCC (International Collaborative Group): The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) - results of an international collaborative study. Fam Cancer 2001, 1:87-92.
• [24]de Jong AE, van Puijenbroek M, Hendriks Y, Tops C, Wijnen J, Ausems MGEM, Meijers-Heijboer H, Wagner A, van Os TA, Brocker-Vriends AH, Vasen HF, Morreau H: Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer. Clin Cancer Res 2004, 10:972-980.
• [25]Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, Walsh-Vockley C, Petersen GM, Walsh MD, Leggett BA, Young JP, Barker MA, Jass JR, Hopper J, Gallinger S, Bapat B, Redston M, Thibodeau SN: Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002, 20:1043-1048.
• [26]Debniak T, Kurzawski G, Gorski B, Kladny J, Domagala W, Lubinski J: Value of pedigree/clinical data, immunohistochemistry and microsatellite instability analyses in reducing the cost of determining hMLH1 and hMSH2 gene mutations in patients with colorectal cancer. Eur J Cancer 2000, 36:49-54.