Comparative Study of Histologic and Chromosomal Abnormalities in Cervical Neoplasia

Abstract

T h e chromosome patterns of 124 cases of cervical intraepithelial neoplasia (dysplasia and carcinoma in situ) and 87 cases of invasive carcinoma of the cervix were examined with the direct squash technique. Diploid or near diploid modes occurred exclusively in the dysplasias. Heteroploidy occurred in both carcinoma in situ and invasive carcinoma but the majority of cases of carcinoma in situ exhibited near tetraploid modes whereas the majority of invasive carcinomas had modes in the near diploid range. These differences were significantly different (P<O.OOl), as were the differences in chromosome pattern in small cell and large cell lesions, both in situ and invasive. Chromosome patterns also showed some correlation with the types of abnormal mitoses in histologic section. A considerable number of cases of carcinoma in situ and invasive carcinoma did not exhibit a mode although modes were common in stage I and stage I V carcinoma. These results are discussed i n relation to the progression of preinvasive lesions. HE CHROMOSOME NUMBER OF MANY HU-T man and animal neoplasms has been studied in detail with both direct squash preparations and in vitro cultures.12-14 I n contrast, relatively little is known of the changes in chromosome number and morphology which occur in the earliest stages of neoplasia, particularly in the so-called precancerous lesions. In humans this is due in a very large extent to difficulties in detection and biopsy of such lesions.The cervix uteri of women is an exception to this rule since, in this organ, effective detection of the lesion is possible with the widespread application of the cervico-vaginal smear and, due to the situation of the organ, biopsy of such lesions is relatively simple. Chromosome studies of the pre-invasive le-

Cervical papillomaviruses segregate within morphologically distinct precancerous lesions

“…Stained sections from each biopsy were analyzed for the presence of features associated with classical HPV infection (condyloma) and with CIN. The former include epithelial maturation and nuclear atypia in the surface epithelial cells (koilocytotic atypia); the latter include nuclear atypia in all layers of the epithelium and the presence of abnormal mitoses as previously described (4,12,20). Nuclear atypia is defined as hyperchromatism, pleomorphism, anisonucleosis, and coarse chromatin distribution.…”

“…We have previously shown that HPV 16 is present in a unique subset of condylomata which contain abnormal mitoses (5). Abnormal mitoses classically are associated with squamous neoplasms, including carcinomas in situ (12). Results of these studies (5,7) indicate that HPV 16 is associated with different types of precancerous lesions that have certain morphological features in common.…”

Cellular immortality: A late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss

“…Because we demonstrated resistance to both these phenomena in the erythroplakia cultures, we be- Table 1. lieve that this phenotype is an early event in the pathogenesis of SCC-HN and that it contributes to the suprabasal proliferation of dysplastic oral lesions, including erythroplakia [28]. Two senescent carcinoma cultures, BlCR 66 and BlCR 80, and the erythroplakia culture BlCR E5 also possessed numerical chromosome aberrations, which are often associated with progression towards SCC [39]. We have not formally shown that the keratinocytes from BlCR 37, BlCR 66, and BlCR 80 are actually invasive, but because BlCR 37 was isolated from a lymph-node metastasis, we can be confident that this culture is carcinoma derived.…”

The Causes and Consequences of Polyploidy in Normal Development and Cancer

“…The tetraploid state is lost in 1-2 years, consistent with transient tetraploid cells that lose chromosomes at high frequency . Similarly, during the evolution of cervical, breast, and bladder cancer, there is evidence for wholegenome duplication followed by chromosome losses (Dutrillaux et al 1991;Kirkland et al 1967;Olaharski et al 2006;Ottesen 2003;Shackney et al 1995a,b). Tetraploidization also occurs in hyperplastic lesions of the pancreas (Tanaka et al 1984), in localized prostate cancer (Deitch et al 1993, Montgomery et al 1990, Pihan et al 2001, and some colon adenomas (Hamada et al 1988, Levine et al 1991.…”