Two subtypes of mucinous adenocarcinoma of the colorectum: clinicopathological and genetic features.
BACKGROUND
This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent.


METHODS
One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes.


RESULTS
MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) phenotype, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02).


CONCLUSIONS
The results of the present study confirm that MUC represents distinct clinicopathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior.
Leopoldo
Sarli
S
Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University, Medical School, Parma, Italy. leosarli@unipr.it
Lorena
Bottarelli
B
Cinzia
Azzoni
A
Gabriella
Di Cola
DC
Angela Luciana
Barilli
B
Renato
Costi
C
Antonio
Mazzeo
M
Carlo
Salvemini
S
Cristina
Porrini
P
Stefano
Cecchini
C
Maurizio
Taglia
T
Luigi
Roncoroni
R
Cesare
Bordi
B
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D018396:Mucin-1 / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1