Extensive and divergent chromosomal losses in squamous and spindle-cell components of esophageal sarcomatoid carcinoma.
Sarcomatoid carcinoma of the esophagus is an unusual type of squamous cell carcinoma (SCC) with a variable component of sarcomatoid spindle cells (SA). The loss of heterozygosity (LOH) involving multiple cancer-associated chromosomal arms has been reported to have a concerted, rather than an individual, effect on tumor progression. In order to delineate the role of LOH in the evolution of a biphasic tumor, the carcinoma in situ (CIS), invasive squamous cell carcinoma (ISCC), and SA components from a sarcomatoid carcinoma of the esophagus were compared for their clonality and extent of LOH. Forty microsatellite markers on the cancer-associated chromosomes, 3p, 4p, 5q, 8p, 9p, 13q, 17p, and 18q, were used for the polymerase chain reaction-based LOH analysis. All eight sarcomatoid carcinomas tested revealed extensive LOHs, involving an average of seven chromosomal arms. All CIS, ISCC, and SA components carried not only a high-level primary LOH (mean chromosomal involvement, 5.3) in common but also a low-level secondary LOH (mean chromosomal involvement, 1.8) in disparity. Interestingly, more secondary LOHs were always burdened in the CIS (four cases) rather than the matched ISCC. SA had a greater (four cases), equal (one case), or fewer (one case) number of secondary LOHs than ISCC. Given that excessive chromosomal losses may confer a disadvantage for tumor growth or a benefit for a metaplastic transformation, these results suggest that the multidirectional differentiation of a SCC precursor is stimulated by extensive and divergent LOHs acquired at the initial or early stages, and a precursor burdened with excessive LOH either remains in CIS or expands as a SA component.
Kwon
Mi-Seon
MS
Department of Microbiology, College of Medicine, Catholic University, Seoul, Korea.
Hong
Seung-Jin
SJ
Cho
Hyun-A
HA
Ahn
Geung-Hwan
GH
Lee
Seung-Sook
SS
Lee
Kyo-Young
KY
Rhyu
Mun-Gan
MG
D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics / Q000473:pathology
D004273:DNA, Neoplasm