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 less than 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 greater than 1 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).