In vitro hyperdiploidy in dermal fibroblasts: evidence for genetic predisposition in aerodigestive tract cancer

Abstract

A numerical alteration in chromosome complement in human dermal fibroblast cultures, hyperdiploidy with a normal occurrence of tetraploidy (IVH) has been reported (Danes 1984) to be associated with some heritable single tumors including squamous carcinoma of the nasopharynx (Danes 1986). The incidence of IVH was compared in cultures derived from 65 patients with squamous carcinoma in different regions of the aerodigestive tract (ADT) and 32 clinically normal subjects without a family cancer history by 2 different assays, metaphase assay (MA) and flow cytometry (FCM).By MA, none of the 32 normals showed IVH. Of the 65 ADT patients studied, 35 had IVH and 30 did not. By FCM, there were significant differences in the FCM DNA index (p values<0.001) of “IVH” (all normals and 30 ADT patients) and IVH+ ADT patients. The per cent of cells with a DI of 2 and > I could be used to distinguish all IVH˜ from the IVH + subjects and were thus considered to be the parameters of choice in assaying IVH by FCM. None of the subjects studied showed increased in vitro tetraploidy (IVT) which has been associated with some heritable colon cancer syndromes.Irrespective of family cancer history, approximately half (35/65) of the ADT patients had IVH which has been shown to be associated with the in vivo expression of certain heritable tumors. The average age of squamous carcinoma diagnosis was earlier (mean 50 yrs) for the IVH* group than for the IVH˜ADT group (mean 72 yrs).

Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy

“…In the present study, as in the previously published studies (Danes et al, 1987a(Danes et al, , 1987b, IVH was considered to be present (IVHt) if all 3 assays on a cell line gave the following data: 1) by metaphase assay (MA), if more than 4% of the metaphases were altered, excluding tetraploidy; 2) by FCMs if DNA index DI > 1 was > 8%, and 3) by FCMd if D I > 2 was >6%. As previously reported (1987b), the standard deviations (SD) for each of the 3 assay values were small for the IVH-and increased for IVH+ cell samples.…”

“…Previously (Danes et al 1987a(Danes et al , 1987b) the association of IVH+ with a certain tumor has been presented as the percentage of total clinical cases having IVH+. In the present study of 76 SCCA patients, 54% (41/76) were IVH+ as compared to 57% (8/14) in a previous small sample study (Danes et al 1987a). If the patient group was divided according to sex, the incidence WBS approximately the same (57%, 8/14, for females and 54%, 33/62, for males) ( Table 1).…”

“…Dermal fibroblast lines were established by standard culture methods (Danes 1976) using split-thickness skin biopsies from 76 patients with squamous cell carcinoma (SCCA) within the oral cavity (49) and oropharynx (27) and a group of 76 volunteers without a family cancer history who were age-and sex-matched to the SCCA patients ( Table 1). The patients (7 with SCCA in the oral cavity and 7 in the oropharynx) and 32 volunteers whoe IVH status was published previously (Danes et al 1987a) were included in the present paper. The anatomical subdivisions within the oral cavity and oropharynx used are listed in Table 1 Tumors, 1982).…”

“…The established fibroblast lines were maintained as previously described (Danes et al 1987a) prior to assay. Fibroblast subcultures were prepared from each established line and assayed for IVH by 3 different techniques: 1) metaphase assay, MA; 2) flow cytometry of stationary cell cultures…”

“…In the initial studies (Danes et al 1987a), the incidence of IVH in a small sample of 14 patients with SCCA in either the oral cavity or oropharynx was 54% (4/7 patients in each anatomical location). The purpose of this paper is to report on IVH assays on a larger sample (76 patients) and an ageand sex-matched clinically normal group without a family history of an aerodigestive tract tumor.…”