TY - JOUR
T1 - The relationship of quantitative nuclear morphology to molecular genetic alterations in the adenoma-carcinoma sequence of the large bowel
AU - Mulder, Jan Willem R.
AU - Offerhaus, G. Johan A.
AU - De Feyter, Eimert P.
AU - Floyd, Jeffrey J.
AU - Kern, Scott E.
AU - Vogelstein, Bert
AU - Hamilton, Stanley R.
PY - 1992/10
Y1 - 1992/10
N2 - The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homoge-neity, was inversely correlated with progression (r = -0.80, P < 0,0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P ≤ 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes.
AB - The relationship of abnormal nuclear morphology to molecular genetic alterations that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen-stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were characterized by computerized image analysis. Both nuclear area and the nuclear shape factor representing irregularity correlated with adenoma-carcinoma progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear texture, a parameter of chromatin homoge-neity, was inversely correlated with progression (r = -0.80, P < 0,0001). The nuclear parameters were strongly interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were predominantly associated with adenoma-carcinoma progression (P ≤ 0.0001) and were not influenced significantly by the individual molecular genetic alterations. Nuclear texture, however, was inversely correlated with fractional allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P = 0.011). The findings indicate that nuclear morphology in colorectal neoplasms is strongly related to tumor progression Nuclear morphology and biologic behavior appear to be influenced by accumulated alterations in cancer-associated genes.
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M3 - Article
C2 - 1357973
AN - SCOPUS:0026661659
SN - 0002-9440
VL - 141
SP - 797
EP - 804
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -