Biomedical subjects
Publications and source records attributed to N B Atkin.
The appearances are described in 4 human tumours having nuclear protrusions associated with large abnormal chromosomes. In C-banded preparations, chromocentres were seen in the protrusions only where interstitial C-bands were present on the long arm of the abnormal chromosome, providing evidence that the protrusions are indeed formed by the long arms.
Cytogenetic studies on 26 carcinomas of the cervix showed that chromosome 1 was consistently involved in the changes: either one or more structurally abnormal chromosomes or a relative excess of normal chromosomes were present. Several types of structural change were repeatedly seen: short arm deletions (1p-, in seven tumors); long arm isochromosomes (i(1q), in six tumors); and translocations of unidentified chromosomal material onto one of the arms (possibly in eleven tumors; in four of these, there was an additional C-band on the long arm). In one tumor, there was a short arm isochromosome (i(1p)). The most consistent feature of the aneuploid complements of these tumors appeared to be the presence in excess of the centromeric region and at least part of the adjacent heterochromatin of chromosome 1.
The modal DNA values of 1465 tumours, together with other factors of possible prognostic importance, were related to the survival of the patients, using regression models (Kay, 1977). For most tumour sites except the testis, the distributions of modal DNA values were bimodal, with peaks at the diploid level and in the triploid-tetraploid range. For all tumour sites except the cervix uteri, patients in the low (near-diploid) range showed better survival; the reverse was true for squamous-cell carcinoma of the cervix uteri. Other variables showed the following effects: for all sites except the testis, younger patients showed a better survival; for the cervix and corpus uteri, breast and ovary, increasing clinical stage was associated with poorer survival. Where evaluated, histological grade appeared to be associated with survival rate, the less well differentiated tumours having a worse prognosis, except for the breast, where the reverse correlation was noted. For carcinoma of the bladder, females and a poorer survival rate than males.
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Structurally rearranged chromosomes 1 were found in 9 out of 14 ovarian carcinomas and may also have been present in three others. In the remaining two, pericentric inversions involving the heterochromatic regions of chromosomes 1 were seen, and were also identified in one of the chromosomes 1 in the patient's normal cells (lymphocytes). Altogether, heterochromatin variants (variation in size and/or the presence of a pericentric inversion) were seen in the tumour cells of eight cases, and one or both types of variation were identified in the normal cells of six of these. The possibility of an association between the presence of chromosome 1 heterochromatin variants as a constitutional anomaly, a liability to ovarian (and perhaps other forms of) cancer and structural changes involving the chromosomes 1 in the tumour cells is considered.
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The chromosomes of 13 carcinomas of the bladder were studied in C- and G-banded preparations. Heteromorphism for the amount of centromeric heteromorphism on the no. 1 chromosomes was apparent in eight tumours, and in three of these the heteromorphism was also found in the patient's normal cells. In four tumours, there were pericentric inversions of the heterochromatic regions of one or more no. 1 chromosomes. Major structural changes involving no. 1 chromosomes appeared to have occurred in at least seven of the tumours. In addition to the high incidence of heterochromatin variants (known or presumed to be constitutional phenomena), and major structural changes involving the no. 1 chromosomes, a further feature, common to four tumours, was the presence of a heterochromatic minute.
The 5-year survival rates of 540 patients with carcinoma of the cervix and 186 with carcinoma of the corpus uteri were assessed in relation to the modal DNA values of the tumors. Patients with squamous cell cervical carcinomas had more favorable prognoses if the modes were near-triploid or hypotetraploid; however, these high-ploidy tumors included more stage III cases than did the tumors with near-diploid modes. Patients with near-diploid endometrial carcinomas has considerably more favorable prognosis than did patients with the minority of tumors at this site, who had high modes; this prognostic difference was only partly related to a higher proportion of poorly differentiated tumors in the high-ploidy group since, among the poorly differentiated tumors, individuals with near-diploid modes again had significantly better prognoses than those with high modes.
The 5-year survival rate of 78 patients with carcinoma of the ovary showed that the prognosis was significantly better when the tumour modal DNA value was in the diploid region than when it was near-triploid or above. Similar data on 140 patients with carcinoma of the breast and 52 with carcinoma of the bladder also suggested a better prognosis for the near-diploid tumours. Among 105 carcinomas of the large bowel, however, there were more survivors in the high-ploidy than in the near-diploid group, although the difference was not statistically significant. The varying relationship between ploidy and prognosis, depending on the site or histological type of the tumour, is briefly discussed on the basis of the 1171 cases included in the present and a previous paper.
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By use of cell size, protein and hemoglobin content, and enzyme activities as markers, it becomes apparent that in the course of evolution the gene expression of anciently tetraploid fish of the order Ostariophysi was diploidized, but no such regulatory mechanism has evolved in the phylogenetically tetraploid species of the order Isospondyli. This finding is discussed in terms of possible selective neutrality of tetraploid expression and the phylogenetic age of Isospondyli.
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