Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.
BACKGROUND
Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses shows microscopic features indistinguishable from colorectal cancer. Our aim was to verify whether the morphologic resemblances mirror genetic profile similarities.


METHODS
Twenty consecutive surgically treated ITAC cases, previously investigated for p16(INK4a) and TP53, were investigated for hMLH1, hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations.


RESULTS
One case was immunonegative for both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong beta-catenin overexpression. No BRAF and APC truncating mutations were identified, whereas K-ras mutations were detected in 9 ITACs (50%).


CONCLUSIONS
Our data confirm the phenotypic similarities at the genetic level between colorectal cancer and ITACs showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome 18q. By contrast, both frequency rate and type of inactivation of the APC-beta-catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in the early development of ITAC (p16(INK4a) and TP53) and colorectal cancer (APC).
Frattini
Milo
M
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Perrone
Federica
F
Suardi
Simona
S
Balestra
Debora
D
Caramuta
Stefano
S
Colombo
Federica
F
Licitra
Lisa
L
Cantù
Giulio
G
Pierotti
Marco A
MA
Pilotti
Silvana
S
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D053843:DNA Mismatch Repair; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009296:Nasal Cavity; D009669:Nose Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010255:Paranasal Sinus Neoplasms / Q000235:genetics*; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein