Natalia Rodon1, Olga Diaz1, Carme Pubill1,2, Cristina Saucedo1, Estefanía García3, Eugeni Saigí3
and Xavier Puig1,2,4.
1BIOPAT. Biopatologia Molecular SL. Grup Assistència. Barcelona, Spain, 2HISTOPAT SL. (Grupo CERBA). Barcelona,
Spain. Servicios de 3Oncologia y 4Patología. SCIAS-Hospital de Barcelona, Grup Assistència. Barcelona, Spain.
Introduction
Cancer of unknown primary (CUP) is an aggressive neoplasia with a high mortality rate. Analyzing CUP molecular
profiles with a NGS-based panel could be helpful as some molecular alterations may provide clues regarding the
putative primary site of each tumor. Moreover, knowing these alterations could benefit patients as they may direct
a specific target therapy or being an inclusion criterion for clinical trials. In the present study, the real contribution
of tumor molecular profiles to establish the primary site and it’s capability to indicate a target therapy in a clinical
diagnostics laboratory was analyzed.
Methods
A retrospective study was designed. All CUP analyzed in our center between August 2022 and August 2023 were
included. The morphological diagnosis included a wide panel of immunohistochemical studies. The molecular profile
was performed with an NGS panel analyzing alterations in 161 genes at DNA and RNA level (Oncomine
Comprehensive v3 Panel. ThermoFisher) Mutations, indels, CNV and gene fusions were recorded.
Results
Sixty-three patients with a CUP diagnosis were included (55.6% males. Median age 73.5), 48 corresponding to
biopsies and 15 to cytological samples. Liver (23.8%) was the organ most represented followed by peritoneum
(17.4%) and lung (15.8%). In 2 (3.2%) specimens a molecular profile was not established due to a low yield of the
DNA and RNA extracted. In 45 (73.8%) cases at least one molecular alteration was detected (range 1 to 6 coexisting
alterations). Only 3 fusions affecting ALK, FGFR3 and TMPRSS2 were detected in 3 different patients. Eighty-six
mutations were detected in 30 different genes, being TP53 (20.9%), KRAS (16.3%) and ARID1A (5.8%) the most
prevalent. Twenty-three amplifications were detected in 14 different genes, being MDM2 (21.7%) and CDK4 (13%)
the most prevalent. The molecular profile helped to establish the primary tumor site in 23 patients (51.1%) and
could indicate a target therapy or the inclusion of the patient in a clinical trial in 44 (97.8%) of the 45 patients who
presented molecular alterations.
Conclusions
NGS-based panel molecular profiling of CUP allows the high sensitivity detection of DNA and RNA alterations in a
broad number of genes, simultaneously. The molecular alterations detected reports clinically relevant information
for a wide range of CUP patients in this series. Molecular profile could help establish the primary tumor site and/or
direct a specific target therapy either by clinical guidelines indication or by being an inclusion criterion in a clinical
trial.
Abstract exhibited at the:
AMP Europe Congress 2024
Madrid, June 24-26, 2024