Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance.
Sinonasal adenocarcinomas, a relatively rare entity, are composed of distinctly different morphologic subtypes with variable biological behavior. To investigate the genetic events associated with their development and clinicopathologic features, we analyzed the alterations in K-ras, APC, beta-catenin, hMLH1 and hMSH2 and p53 genes expression in a cohort of 15 primary tumors comprising the two main sinonasal adenocarcinoma subtypes (enteric and seromucinous). The patients consisted of 13 men and two women, who ranged in age from 50 to 87 years. Tumors were predominantly located in the ethmoid sinus. Eight tumors were Enteric-type, and seven were seromucinous type. Nine patients were smokers and four were nonsmokers; and no information was available on two patients. Two of the eight enteric-type, had K-ras mutation at codons 12A and 12B, and one showed microsatellite instability at BAT-25. Two patients with enteric-type tumors had a history of wood-dust exposure, and one had a K-ras mutation at 12A codon as well as p53 overexpression. No patients with the seromucinous type had any genetic abnormalities, except for overexpression of p53 in two tumors. Our results show that (1) a subset of enteric-type sinonasal adenocarcinoma shares certain genetic alterations with colonic adenocarcinomas, (2) the seromucinous-type sinonasal adenocarcinoma lacks alterations and may develop through a different pathway, (3) high p53 expression is associated with aggressive tumor features in both subtypes and (4) the enteric-type runs a more malignant course than the seromucinous counterpart.
Yom
Sue S
SS
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rashid
Asif
A
Rosenthal
David I
DI
Elliott
Danielle D
DD
Hanna
Ehab Y
EY
Weber
Randal S
RS
El-Naggar
Adel K
AK
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D010255:Paranasal Sinus Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D018631:ras Proteins