ABSTRACT
Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies-IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies.
ABSTRACT
OBJECTIVES: There is growing interest in the biological and molecular features and neoplastic potential of colonic hyperplastic polyps because of the recent finding of K-ras mutations in many of these lesions. Hyperplastic polyps may also develop in chronic ulcerative colitis (CUC), but it is unclear if these are biologically similar to the sporadic type. The aim of this study was to evaluate and compare the molecular profile of CUC-associated hyperplastic polyps with sporadic hyperplastic polyps of the colon. METHODS: Thirty-nine hyperplastic polyps from 26 CUC patients, 39 sporadic hyperplastic polyps from 29 age- and sex-matched patients without CUC, and 26 colonic mucosal biopsies from 22 patients with CUC but without hyperplastic polyps were analyzed by polymerase chain reaction for loss of heterozygosity of APC, 3p, p53, and p16 and for mutations in codons 12, 13, and 61 of the K-ras gene. Immunohistochemical evaluations for the proliferation-associated nuclear peptide Ki67 (MIB-1) and p27 were also performed on a subset of hyperplastic polyps. RESULTS: CUC-associated hyperplastic polyps showed a proportion of genetic alterations (47%) similar to that of sporadic hyperplastic polyps (33%) (p > 0.05), and neither significantly differed from chronically inflamed mucosae in CUC patients without hyperplastic polyps. Furthermore, in a small group of CUC patients in which informative tissue was available from both their hyperplastic polyps and adjacent flat colitic mucosae, the polyps contained mutations that were not present in the underlying mucosa. Loss of heterozygosity of APC, 3p, p53, p16, and K-ras mutations were present in 21%, 40%, 27%, 20%, and 19% of CUC patients with hyperplastic polyps, respectively, and in 0%, 11%, 20%, 13%, and 13% of non-CUC patients with sporadic polyps, respectively. Both CUC-associated and sporadic hyperplastic polyps showed a substantial number of cases (46% and 64% of cases, respectively) with loss of p27 expression, and both types of lesions showed similar MIB-1 proliferation indices. CONCLUSIONS: These data suggest that CUC-associated hyperplastic polyps are genotypically similar to the sporadic type. This study adds to the expanding list of molecular alterations that have been discovered in hyperplastic polyps, and lends further support to the controversial theory that these lesions may have neoplastic potential.
