In:
Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 149, No. 8 ( 2023-07), p. 5289-5300
Abstract:
FGFR2 is a therapy-relevant target in tumors of the upper gastrointestinal tract (GIT), and clinical trials are currently underway to test the efficacy of FGFR2 inhibitors. Tumor heterogeneity is one of the relevant causes of treatment failure. Almost nothing is known about the heterogeneous distribution of FGFR2 -amplified clones in adenocarcinomas of the upper GIT. Patients and methods To assess FGFR2 gene copy number alteration and intratumoral heterogeneity of upper GIT adenocarcinomas, we analyzed 893 patient-derived formalin-fixed paraffin-embedded tumor specimens, including primary operated and neoadjuvant-treated tumors (462 gastric carcinomas and 429 esophageal adenocarcinomas) as well as complementary lymph node and distant metastasis by fluorescence in situ hybridization. Results Twenty-six gastric tumors (5.6%) and 21 esophageal adenocarcinomas (4.9%) showed FGFR2 amplification. Overall, 93% of gastric carcinomas and 83% of esophageal carcinomas showed heterogeneous amplification. FGFR2 amplification was found in different histological growth patterns, including intestinal and diffuse type according to the Lauren classification. In the primary gastric carcinoma group, FGFR2 amplification was associated with poor prognosis ( p = 0.005). Conclusion Homogeneous FGFR2 amplification in tumors of the upper GIT is the exception. This has highly relevant implications in the nature of FGFR2 diagnostics (sufficient tumor cell number, determination of amplification at metastasis versus primary tumor, etc.) and on the response probability of appropriate inhibitors. It is relevant that the often poorly treatable and aggressive subtype of diffuse carcinomas (poorly cohesive carcinomas) also shows FGFR 2 amplification and that an individualized therapy option with FGFR2 inhibitors could be an option in this group.
Type of Medium:
Online Resource
ISSN:
0171-5216
,
1432-1335
DOI:
10.1007/s00432-022-04460-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
1459285-X
