Mucinous adenocarcinomas: poor prognosis in metastatic colorectal cancer.
OBJECTIVE
Mucinous histology of metastatic colorectal cancer (CRC) has been associated with poor prognosis, however this has never been assessed in large well-defined study populations treated with the current used systemic agents. We investigated the prognostic value of mucinous histology in two large phase III studies in metastatic CRC.


METHODS
The study population included 1010 metastatic CRC patients who were treated with chemotherapy and targeted therapies in two phase III studies. Patients were classified according to the histology of the primary tumour in mucinous adenocarcinomas (MC) and non-mucinous adenocarcinomas (AC).


RESULTS
Patients with MC (n=99) were older, had more often a normal serum lactate dehydrogenase (LDH), extrahepatic localisation of metastases, larger primary tumour diameter and a higher T classification compared to patients with AC (n=911). A deficient mismatch repair system and BRAF mutations were observed in 17% and 22% of patients with MC, compared to 3% and 7% in patients with AC, respectively. Clinical outcome was investigated in both studies separately, showing a worse overall survival (OS), progression free survival and overall response rate in patients with MC compared to patients with AC. Patients with MC received less cycles of treatment compared to AC, but did not suffer from a higher incidence of grade 3/4 toxicity. In multivariate analysis, mucinous histology was as an independent negative prognostic factor for OS, resulting in a combined hazard ratio of 1.78 (95%confidence interval (CI) 1.35-2.35).


CONCLUSIONS
Patients with metastatic mucinous CRC have distinct clinicopathological features and poor response to chemotherapy and targeted agents. The strong negative prognostic value of MC warrants the use of this pathological feature as a stratification factor for clinical trials in metastatic CRC.
Department of Pathology, Radboud University Nijmegen Medical Centre, The Netherlands.
Leonie J M
LJ
Mekenkamp
Karin J
KJ
Heesterbeek
Miriam
M
Koopman
Jolien
J
Tol
Steven
S
Teerenstra
Sabine
S
Venderbosch
Cornelis J A
CJ
Punt
Iris D
ID
Nagtegaal
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012189:Retrospective Studies