PATHOLOGY AND GENETIC TESTING - WORKSHOP NO.6

By reporting on the possible existence of a hereditary cancer and reco mmending further genetic evaluation, the pathologist can help identify families with hereditary cancer. Currently, however, recognition of a case of hereditary cancer relies predominantly on clinical criteria, as common cancers show only a few specific pathologic features that su ggest hereditary predisposition. Furthermore, clinical criteria alone often fail to identify mutant gene carriers. In contrast to genes that have a high penetrance for causing cancer, such as BRCA1, APC, RET, a nd the mismatch repair genes, identifying carriers of mutant genes hav ing a lower penetrance (as is the case for the BRCA2 gene) is more dif ficult. Studies to identify markers for mutant germline cancer-predisp osing genes will typically require studying archival tissue specimens, but germline genetic testing on archival samples for research purpose s is complicated by the need for patient consent unless specimens are stripped of their patient identifiers. Pathologists contemplating such research should seek informed consent for genetic testing prior to ar chiving tissues. The need for consent has led to concerns that certain types of cancer research projects will no longer be feasible; if pati ent consent has not been obtained, however, institutional review board -approved protocols that facilitate obtaining patient clinical data wh ile maintaining patient confidentiality can overcome this problem. As clinical genetic testing for hereditary cancer becomes part of clinica l practice, there are many concerns about the quality of service at ea ch step in the process, One of the most important requirements for qua lity is to ensure that the performance of a generic test is always lin ked to adequate pretest and posttest genetic counseling. Reporting of genetic test results should be standardized and include information ab out the technique used to identify mutations, the sensitivity and spec ificity of the test in detecting such mutations, and the limitations o f the test. The report should also contain recommendations for further action and information packets to assist in the interpretation of the test. Pathologists have expertise in the area of laboratory proficien cy testing and can play an important role in the establishment of a na tional proficiency program to ensure a quality genetic testing process . (C) 1997 American Cancer Society.