F-box and WD repeat domain-containing 7 (FBXW7) mRNA and outcome in biliary tract cancer.

Abstract

e14521 Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.

Cáncer de vesícula biliar

“…El Intergrupo Latinoamericano de Oncología Gastrointestinal (ILOGI) analizó el estado transcripcional de genes que pueden ser usados como factores con valor predictivo y pronóstico en 54 muestras de pacientes con cáncer de vías biliares [incluidos CVB, colangiocarcinoma (CC) y cáncer de la ampolla de Vater]. Entre estos, los niveles de ARN mensajero (ARNm) de FBXW7, un gen que codifica para una ubiquitina ligasa que interacciona con oncoproteínas, se correlacionaron con la supervivencia libre de progresión y SG en 19 pacientes 47 . La mediana de SLP fue 4.9, 7.6 y 26.9 meses para los tumores con niveles de expresión de FBXW7 en los tercilos bajo, medio y alto, respectivamente; la mediana de SG fue 6.2, 8.8 y no alcanzada, respectivamente.…”

Gallbladder cancer: South American experience

“…The Gastrointestinal Oncology Latin-American Intergroup (ILOGI) analyzed the transcriptional level of different genes as predictive or prognostic factors in 54 BTC samples (including GBC, CC and ampullary cancer). Among others the mRNA level of FBXW7 a gene that encodes an ubiquitin ligase that interacts with oncoproteins, correlated with progression free survival (PFS) and overall survival (OS) in 19 patients (47). Median PFS was 4.9, 7.6 and 26.9 months for tumors in the lowest, middle and upper tercile of expression level.…”

Commentary on Gallbladder Cancer: South American Experience

“…Dr. Parada, and outstanding geneticist in Salta, was invited to write the second part of the article. Dr. Parada, who has been working in basic research on hepatobiliary cancer for many years, reviewed the current literature and found that many risk factors and molecular abnormalities of GC have been described by investigators from South America [4][5][6][7][8][9][10]. The third part, which I analysed, was related to the clinical experience.…”