H-ras mutation is an additional event of sarcomatous transformation in aerodigestive spindle cell carcinoma.
The conversion from a carcinomatous component to a sarcomatous one in spindle cell carcinoma (SPCC) of the upper aerodigestive tract is thought to occur via a series of molecular alterations; however the detailed mechanism is still unknown. We examined mutations at the H-ras and p53 genes in 16 SPCCs of upper aerodigestive tracts using PCR-RFLP, PCR-SSCP and direct sequencing analysis. The two distinct components, sarcomatous and carcinomatous components in SPCC, were analyzed independently. p53 mutations were detected in both components of SPCC (50.0%, 8/16), and those in the sarcomatous component were completely in accordance with those in the carcinomatous one. In contrast, H-ras mutations were detected only in the sarcomatous component (12.5%, 2/16), and not in the carcinomatous one (0%, 0/16). There was a statistically significant difference in prognosis between the patients with the H-ras mutation (n=2) and those without (n=14); the former had poorer prognosis (P=0.0049). Our results seem to suggest that the H-ras mutation is a relatively uncommon event in SPCC; however, the presence of H-ras mutations may be associated with a more malignant potential in SPCC, while actually occurring during the sarcomatous change itself.
Shiratsuchi
Hideki
H
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hirakawa
Naoya
N
Saito
Tsuyoshi
T
Oda
Yoshinao
Y
Yamamoto
Hidetaka
H
Tomita
Kichinobu
K
Yamamoto
Tomoya
T
Tsuneyoshi
Masazumi
M
D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic; D003062:Codon; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012142:Respiratory Tract Neoplasms / Q000235:genetics* / Q000401:mortality; D012509:Sarcoma / Q000235:genetics* / Q000401:mortality; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D013997:Time Factors
D003062:Codon; D004247:DNA