Originally published as JCO Early Release 10.1200/JCO.2009.22.0731 on March 23 2009

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Comprehensive Screening for Lynch Syndrome: Who Can Be the Driving Force in Daily Clinical Practice?

Institute for Microbiology and Pathology, Donauspital Vienna, Austria

Michael R. Speicher

Institute of Human Genetics, Medical University of Graz, Graz, Austria

Angelika Reiner-Concin

Institute for Microbiology and Pathology, Donauspital Vienna, Austria

Gerald Hoefler

Institute of Pathology, Medical University of Graz, Graz, Austria

To the Editor:

With great interest we have read the recently published article by Hampel et al¹ on the feasibility of screening for Lynch syndrome (LS) among patients with colorectal cancer. While no doubt exists that many individuals could benefit from systematic screening tests for LS, it is surprising that establishing such a test in routine diagnostics has not yet been accomplished in many institutions. Here, we would like to add a pathologist's perspective on the obstacles that still hamper the introduction of comprehensive colorectal cancer screening programs in so many countries, including our own. Many publications have already addressed the issue of using medical histories to preselect patients for LS screening. However, in our experience, obtaining the necessarily extensive medical histories is often impossible in daily practice due to time constraints for many physicians working in surgical or gastroenterological clinics. The problem is aggravated by the fact that histologic specimens are often referred to histology laboratories from different hospitals, making a standardized, detailed report that considers medical histories even more difficult to complete. This rather pessimistic view is reinforced by our own recent study: despite the surgeons' awareness of the possible presence of LS in a series of over 700 patients with colorectal cancer we have worked up in a multicenter feasibility trial for LS screening across Austria, not a single patient had been referred to histological examination by clinicians as potential LS. Hampel et al¹ obviously made the same experience stating that only one out of 153 LS patients (probands and relatives combined) had been referred by a clinician. Consequently, the risk for a LS patient to remain undetected is currently extremely high, presumably not only in Austria. Considering that a driving force to identify high-risk LS subgroups in daily practice has not emerged for years, the question arises—who should perform this important task?

For reasons of practical feasibility, in our opinion, LS screening should be systematically done on all colorectal cancers (molecular strategy). The present report reinforces that DNA mismatch repair enzyme immunohistochemistry is suitable as the first-line approach, followed by microsatellite analysis if appropriate. Importantly, the results of the tests should be incorporated in every single primary colorectal cancer histopathology report. This should have two effects critical to gain momentum needed for LS screening: First, it will set a standard within the pathologists' community and extend the current work-up of colorectal cancer samples. Secondly, mentioning a potentially hereditary mismatch repair deficiency in the written report will create the (legal) necessity for further action. As the molecular strategy is focused on the surgical specimen as the starting point, the reporting pathologist is ideally positioned to be the initial driving force in LS screening. In this scenario, the pathologists take responsibility for the detection of individuals who may have an increased risk for a tumor-prone hereditary disease. We believe that such patients are then to be counseled by a multidisciplinary team consisting of a human geneticist and a surgeon to enable them to reach an informed decision for further diagnostic procedures, such as germline DNA analysis and a personalized risk-stratified follow-up. Such efforts should increase the chance that screening is perceived by the patient as a valuable, well-coordinated service and not as an imposed nuisance. As a consequence, reaching out to possibly affected relatives is more likely to be successful, thereby increasing overall efficiency of the program. All three specialists involved—surgeons, pathologists, and human geneticists—would ideally be aided by the interdisciplinary teamwork and guidelines of their respective professional societies addressing steps to be taken. The strategy outlined here could help to reduce the presently existing vacuum of responsibility everybody expects others to fill. We are currently in the process to introduce national guidelines for the Austrian Society for Pathology to overcome this problem recommending DNA mismatch repair enzyme immunohistochemistry in every case of colorectal carcinoma. From past experience, it might now be the pathologist's turn to represent the initial driving force to take LS screening from the trial phase to where we think it belongs—the daily clinical practice.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCE

1. Hampel H, Frankel WL, Martin E, et al: Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 26:5783–5788, 2008.[Abstract/Free Full Text]

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