KRASMutant Status May Be Associated with Distant Recurrence in Early-stage Rectal Cancer.
Total mesorectal excision combined with neo-adjuvant chemoradiotherary (CRT) and adjuvant chemotherapy, has been the standard treatment of locally advanced rectal cancer (LARC). Although TNM (Tumor, Node, Metastasis) classification for malignant Tumors is still the cornerstone in rectal cancer staging, there has been an effort to identify molecular biomarkers with additional prognostic or predictive value.



We retrospectively analyzed molecular biomarkers on prospectively collected histological specimens and clinical data from a cohort of 135 consecutive rectal cancer cases who underwent radical excision in a tertiary center between 2011-2014 (males=87, females=48, age range=22-89 years, mean=64,67 years, SD=13.40). Radiological, histopathological, molecular staging, treatment stratification by the multidisciplinary team (MDT), as well as prognostic outcome data were compared with various biomarkers including KRAS, BRAF, p16, b-catenin, MSI, MMR and MGMT.



The mean follow-up was 39.21 months (range=5-83 months, SD=21.34). Twenty-eight cases were Stage I (20.9%), n=30 Stage II (22.4%), n=45 Stage III (33.6%) and n=31 Stage IV (23.1%). Forty specimens were KRAS-mutant (mt) (37.4%) while n=67 (62.6%) wild type (wt). KRAS mt status was associated with female sex (n=20, p=0.021) and older age (69.62 vs. 62.27, p=0.005). Stage I Early Cancer Subgroup analysis showed that KRAS mt status is associated with distant recurrence of disease (n=4, p=0.045).



KRAS mt status may affect the prognosis of early rectal cancer, as this is linked with distant recurrence.
Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
Michail
M
Sideris
Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
Jane
J
Moorhead
Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
Salvador
S
Diaz-Cano
Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
Amyn
A
Haji
Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K. spapagrigoriadis@nhs.net.
Savvas
S
Papagrigoriadis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
KRAS; Molecular biomarkers; early rectal cancer; recurrence